PHOENIX — The opportunity to diagnose eosinophilic esophagitis (EoE) when patients present to the emergency department (ED) with the classic symptom of esophageal food impaction (EFI) is commonly missed, with necessary biopsies provided at strikingly low rates, despite guideline recommendations, new research showed.

“This is the first study to assess the rate of biopsies at time of esophageal food impaction in a large, real-world dataset of community practices,” the authors explained in research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The findings underscore that “clinicians should remember to perform esophageal biopsies during endoscopy for esophageal food impaction.”

Research shows patients with EoE, a chronic and progressive type 2 inflammatory disease, have an average delay of 4 years before being diagnosed, with a delay of up to 10 years in about a third of cases. With those delays comes the likelihood of disease progression.

The latest guidelines from the ACG indicate that for diagnosis, “from a practical standpoint,” the preferred approach is to obtain at least two to four biopsies from at least two distinct esophageal areas, while targeting areas of visual inflammation.

However, prior evidence suggests that the biopsies are commonly not performed when patients present with the symptoms of EFI.

To further investigate the management of EFI during and after ED visits in a real-world setting, first author Walker D. Redd, MD, Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, North Carolina, and colleagues conducted a retrospective cohort study of 2566 patients in a multistate gastrointestinal practice group at 143 care centers in seven US states.

The patients were treated for esophageal food or foreign body removal between 2018 and 2024.

Among them, 1434 patients received evaluation with esophagogastroduodenoscopy (EGD), with 754 having no EGD and 378 receiving EGD for non-EFI.

The patients had a mean age of 63, with nearly 60% being older than 60 years, and 44.9% were women.

At the index EGD, only 19% had records of having esophageal biopsies. Among them, nearly half, 47%, were determined to have biopsy-confirmed EoE.

Of those who did not receive biopsies, only 7% had records of having received a follow-up EGD with an esophageal biopsy within 1 year, with 40% of those having EoE confirmed from a biopsy.

Among the remaining 93% of patients who had no record of such follow-up care within 1 year, 41% were lost to follow-up.

“We found that only about one fifth of patients had esophageal biopsies collected at the time of esophageal food impaction, which is similar to previous reports,” Redd said.

Overall, “esophageal biopsy rates at the time of esophageal food impaction remain low, and follow-up EGD with biopsy rates are also very low.”

Responding to a comment from the audience, Redd agreed that a limitation of the study was the scenario of patients from out of town being treated at an ED and then going back home, where their follow-up status may not be known.

Nevertheless, awareness of the low rates “represent an important opportunity to reduce the diagnostic delay and improve quality of care in EoE,” he said.

Commenting on the study, Danny Issa, MD, an interventional gastroenterologist at UCLA Health, agreed that the low rates of follow-up were troubling.

“Only 1 in 10 is a very low rate of follow-up endoscopy,” he told GI & Hepatology News.

“These results show we need to encourage quality improvement initiatives to make sure those patients are followed up,” he said.

Furthermore, “additional studies are needed to better understand the barriers behind the lack of follow-up, which were not addressed fully in the study.”

Co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist at Valley Medical Group, in Paramus, New Jersey, added that “the point that needs to be made is that these patients need biopsies so you can diagnose and subsequently treat them.”

Redd reported having a consulting relationship with Sanofi. Issa reported having relationships with Boston Scientific and Eli Lilly. Chokhavatia had no disclosures to report.

A version of this article first appeared on Medscape.com.

PHOENIX — The opportunity to diagnose eosinophilic esophagitis (EoE) when patients present to the emergency department (ED) with the classic symptom of esophageal food impaction (EFI) is commonly missed, with necessary biopsies provided at strikingly low rates, despite guideline recommendations, new research showed.

“This is the first study to assess the rate of biopsies at time of esophageal food impaction in a large, real-world dataset of community practices,” the authors explained in research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The findings underscore that “clinicians should remember to perform esophageal biopsies during endoscopy for esophageal food impaction.”

Research shows patients with EoE, a chronic and progressive type 2 inflammatory disease, have an average delay of 4 years before being diagnosed, with a delay of up to 10 years in about a third of cases. With those delays comes the likelihood of disease progression.

The latest guidelines from the ACG indicate that for diagnosis, “from a practical standpoint,” the preferred approach is to obtain at least two to four biopsies from at least two distinct esophageal areas, while targeting areas of visual inflammation.

However, prior evidence suggests that the biopsies are commonly not performed when patients present with the symptoms of EFI.

To further investigate the management of EFI during and after ED visits in a real-world setting, first author Walker D. Redd, MD, Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, North Carolina, and colleagues conducted a retrospective cohort study of 2566 patients in a multistate gastrointestinal practice group at 143 care centers in seven US states.

The patients were treated for esophageal food or foreign body removal between 2018 and 2024.

Among them, 1434 patients received evaluation with esophagogastroduodenoscopy (EGD), with 754 having no EGD and 378 receiving EGD for non-EFI.

The patients had a mean age of 63, with nearly 60% being older than 60 years, and 44.9% were women.

At the index EGD, only 19% had records of having esophageal biopsies. Among them, nearly half, 47%, were determined to have biopsy-confirmed EoE.

Of those who did not receive biopsies, only 7% had records of having received a follow-up EGD with an esophageal biopsy within 1 year, with 40% of those having EoE confirmed from a biopsy.

Among the remaining 93% of patients who had no record of such follow-up care within 1 year, 41% were lost to follow-up.

“We found that only about one fifth of patients had esophageal biopsies collected at the time of esophageal food impaction, which is similar to previous reports,” Redd said.

Overall, “esophageal biopsy rates at the time of esophageal food impaction remain low, and follow-up EGD with biopsy rates are also very low.”

Responding to a comment from the audience, Redd agreed that a limitation of the study was the scenario of patients from out of town being treated at an ED and then going back home, where their follow-up status may not be known.

Nevertheless, awareness of the low rates “represent an important opportunity to reduce the diagnostic delay and improve quality of care in EoE,” he said.

Commenting on the study, Danny Issa, MD, an interventional gastroenterologist at UCLA Health, agreed that the low rates of follow-up were troubling.

“Only 1 in 10 is a very low rate of follow-up endoscopy,” he told GI & Hepatology News.

“These results show we need to encourage quality improvement initiatives to make sure those patients are followed up,” he said.

Furthermore, “additional studies are needed to better understand the barriers behind the lack of follow-up, which were not addressed fully in the study.”

Co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist at Valley Medical Group, in Paramus, New Jersey, added that “the point that needs to be made is that these patients need biopsies so you can diagnose and subsequently treat them.”

Redd reported having a consulting relationship with Sanofi. Issa reported having relationships with Boston Scientific and Eli Lilly. Chokhavatia had no disclosures to report.

A version of this article first appeared on Medscape.com.

PHOENIX — The opportunity to diagnose eosinophilic esophagitis (EoE) when patients present to the emergency department (ED) with the classic symptom of esophageal food impaction (EFI) is commonly missed, with necessary biopsies provided at strikingly low rates, despite guideline recommendations, new research showed.

“This is the first study to assess the rate of biopsies at time of esophageal food impaction in a large, real-world dataset of community practices,” the authors explained in research presented at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The findings underscore that “clinicians should remember to perform esophageal biopsies during endoscopy for esophageal food impaction.”

Research shows patients with EoE, a chronic and progressive type 2 inflammatory disease, have an average delay of 4 years before being diagnosed, with a delay of up to 10 years in about a third of cases. With those delays comes the likelihood of disease progression.

The latest guidelines from the ACG indicate that for diagnosis, “from a practical standpoint,” the preferred approach is to obtain at least two to four biopsies from at least two distinct esophageal areas, while targeting areas of visual inflammation.

However, prior evidence suggests that the biopsies are commonly not performed when patients present with the symptoms of EFI.

To further investigate the management of EFI during and after ED visits in a real-world setting, first author Walker D. Redd, MD, Center for Gastrointestinal Biology and Disease, UNC School of Medicine, Chapel Hill, North Carolina, and colleagues conducted a retrospective cohort study of 2566 patients in a multistate gastrointestinal practice group at 143 care centers in seven US states.

The patients were treated for esophageal food or foreign body removal between 2018 and 2024.

Among them, 1434 patients received evaluation with esophagogastroduodenoscopy (EGD), with 754 having no EGD and 378 receiving EGD for non-EFI.

The patients had a mean age of 63, with nearly 60% being older than 60 years, and 44.9% were women.

At the index EGD, only 19% had records of having esophageal biopsies. Among them, nearly half, 47%, were determined to have biopsy-confirmed EoE.

Of those who did not receive biopsies, only 7% had records of having received a follow-up EGD with an esophageal biopsy within 1 year, with 40% of those having EoE confirmed from a biopsy.

Among the remaining 93% of patients who had no record of such follow-up care within 1 year, 41% were lost to follow-up.

“We found that only about one fifth of patients had esophageal biopsies collected at the time of esophageal food impaction, which is similar to previous reports,” Redd said.

Overall, “esophageal biopsy rates at the time of esophageal food impaction remain low, and follow-up EGD with biopsy rates are also very low.”

Responding to a comment from the audience, Redd agreed that a limitation of the study was the scenario of patients from out of town being treated at an ED and then going back home, where their follow-up status may not be known.

Nevertheless, awareness of the low rates “represent an important opportunity to reduce the diagnostic delay and improve quality of care in EoE,” he said.

Commenting on the study, Danny Issa, MD, an interventional gastroenterologist at UCLA Health, agreed that the low rates of follow-up were troubling.

“Only 1 in 10 is a very low rate of follow-up endoscopy,” he told GI & Hepatology News.

“These results show we need to encourage quality improvement initiatives to make sure those patients are followed up,” he said.

Furthermore, “additional studies are needed to better understand the barriers behind the lack of follow-up, which were not addressed fully in the study.”

Co-moderator Sita S. Chokhavatia, MD, AGAF, a gastroenterologist at Valley Medical Group, in Paramus, New Jersey, added that “the point that needs to be made is that these patients need biopsies so you can diagnose and subsequently treat them.”

Redd reported having a consulting relationship with Sanofi. Issa reported having relationships with Boston Scientific and Eli Lilly. Chokhavatia had no disclosures to report.

A version of this article first appeared on Medscape.com.

Patients with gallstone disease blocking the bile duct (choledochlithiasis) who do not have gall bladder removal in the same hospital admission as endoscopic retrograde pancreatography (ERCP) have as much as a 17-fold increase in the risk for biliary complications, regardless of the receipt of sphincterotomy or stenting, new research showed.

“These findings suggest an opportunity for systemic interventions, including prioritization algorithms and better perioperative coordination, to address preventable delays,” reported the authors in the study, presented at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

Choledocholithiasis can occur in up to 20% of symptomatic gallstone cases, and while guidelines recommend having a cholecystectomy concurrently with ERCP, data on the best timing is inconsistent and delays in gall bladder removal are consequently common.

One large study, for instance, the PONCHO trial conducted at 23 hospitals in Netherlands, showed complications to be significantly lower with same-admission vs interval cholecystectomy (4.7% vs 16.9%; P = .02).

Meanwhile, other research has suggested that delayed cholecystectomy is a preferred approach, allowing for removal when there is less inflammation.

Real world data meanwhile shows, despite the guidelines, the procedures are performed at the same time as ERCP only in about 41% of cases, first author Jessica El Halabi, MD, of the Johns Hopkins Hospital, Baltimore, said.

To further investigate outcomes associated with those delays, El Halabi and colleagues conducted a retrospective cohort study involving 507 patients admitted with choledocholithiasis at the hospital and community hospitals between 2005 and 2023 who had 12 months or more follow-up.

The patients had a mean age of 59 years and 59.4% were women.

Of the patients, 265 (52.3%) underwent early cholecystectomy, defined as surgery during the index admission, while 242 (47.7%) underwent delayed cholecystectomy, defined as postdischarge cholecystectomy or if cholecystectomy was not performed.

Overall, biliary complications occurred in as many as 23% of those who had delayed cholecystectomy compared with just 0.8% among those having the early cholecystectomy (P < .001).

Of patients who had delayed cholecystectomy and developed complications, 15.5% did so within 3 months, 6.5% by 6 months, and 1% by 12 months.

Among those who had ERCP with sphincterotomy, there were no significant differences in rates of biliary complications vs those who did not have sphincterotomy (26% vs 21%; P = .74), while stenting also did not reduce the risk (25% vs 27%; P = .81).

The leading reasons for delayed cholecystectomy included patients having a high surgical risk (27.3%), concurrent biliary pathology (19.2%), and physician preference (14%).

The findings underscore that “concurrent cholecystectomy is associated with the lowest risk of biliary complications,” El Halabi said.

“Delayed cholecystectomy is associated with an approximately 23% incidence of biliary complications with 1 year of initial admission, with the highest incidence occurring within 3 months,” she added. “Neither sphincterotomy nor stenting during ERCP mitigates this risk.”

“Early cholecystectomy during the index admission remains the most reliable strategy to reduce recurrent events.”

 

Findings Underscore Importance of Timing

Commenting on the study, Luis F. Lara, MD, division chief of digestive diseases at the University of Cincinnati, who co-moderated the session, agreed that evidence soundly supports early cholecystectomy.

“We also did a large study looking at this and there’s no doubt that doing it during the index admission has a tremendous effect on long-term outcomes,” Lara told GI & Hepatology News.

Lara noted that “part of it is people don’t show up again until they get sick again, so we don’t want to lose that opportunity the first time, during the index admission,” he said.

Lara’s previous studies have specifically documented how early cholecystectomy for acute biliary pancreatitis improves outcomes of hospitalization for cirrhosis and factors associated with early unplanned readmissions following same-admission cholecystectomy for acute biliary pancreatitis.

Akwi W. Asombang, MD, an interventional gastroenterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, both in Boston, agreed that the findings are important.

“We know that if a cholecystectomy is not performed in the same admission as ERCP, the stones in the gallbladder remain and may migrate out into the bile duct, resulting in further complications as described in the study,” Asombang, also a session co-moderator, told GI & Hepatology News.

She noted that the practice can vary between institutions based on factors including the availability of physicians to perform the cholecystectomy.

Potential complications in delaying the procedure can range from inflammation and pancreatitis to obstruction of the bile duct, “which then can result in cholangitis and eventually sepsis or even death,” Asombang cautioned.

“So the timing of the procedure with ERCP is definitely significant,” she said.

El Halabi and Asombang had no disclosures to report. Lara reported a relationship with AbbVie.

A version of this article first appeared on Medscape.com.

Patients with gallstone disease blocking the bile duct (choledochlithiasis) who do not have gall bladder removal in the same hospital admission as endoscopic retrograde pancreatography (ERCP) have as much as a 17-fold increase in the risk for biliary complications, regardless of the receipt of sphincterotomy or stenting, new research showed.

“These findings suggest an opportunity for systemic interventions, including prioritization algorithms and better perioperative coordination, to address preventable delays,” reported the authors in the study, presented at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

Choledocholithiasis can occur in up to 20% of symptomatic gallstone cases, and while guidelines recommend having a cholecystectomy concurrently with ERCP, data on the best timing is inconsistent and delays in gall bladder removal are consequently common.

One large study, for instance, the PONCHO trial conducted at 23 hospitals in Netherlands, showed complications to be significantly lower with same-admission vs interval cholecystectomy (4.7% vs 16.9%; P = .02).

Meanwhile, other research has suggested that delayed cholecystectomy is a preferred approach, allowing for removal when there is less inflammation.

Real world data meanwhile shows, despite the guidelines, the procedures are performed at the same time as ERCP only in about 41% of cases, first author Jessica El Halabi, MD, of the Johns Hopkins Hospital, Baltimore, said.

To further investigate outcomes associated with those delays, El Halabi and colleagues conducted a retrospective cohort study involving 507 patients admitted with choledocholithiasis at the hospital and community hospitals between 2005 and 2023 who had 12 months or more follow-up.

The patients had a mean age of 59 years and 59.4% were women.

Of the patients, 265 (52.3%) underwent early cholecystectomy, defined as surgery during the index admission, while 242 (47.7%) underwent delayed cholecystectomy, defined as postdischarge cholecystectomy or if cholecystectomy was not performed.

Overall, biliary complications occurred in as many as 23% of those who had delayed cholecystectomy compared with just 0.8% among those having the early cholecystectomy (P < .001).

Of patients who had delayed cholecystectomy and developed complications, 15.5% did so within 3 months, 6.5% by 6 months, and 1% by 12 months.

Among those who had ERCP with sphincterotomy, there were no significant differences in rates of biliary complications vs those who did not have sphincterotomy (26% vs 21%; P = .74), while stenting also did not reduce the risk (25% vs 27%; P = .81).

The leading reasons for delayed cholecystectomy included patients having a high surgical risk (27.3%), concurrent biliary pathology (19.2%), and physician preference (14%).

The findings underscore that “concurrent cholecystectomy is associated with the lowest risk of biliary complications,” El Halabi said.

“Delayed cholecystectomy is associated with an approximately 23% incidence of biliary complications with 1 year of initial admission, with the highest incidence occurring within 3 months,” she added. “Neither sphincterotomy nor stenting during ERCP mitigates this risk.”

“Early cholecystectomy during the index admission remains the most reliable strategy to reduce recurrent events.”

 

Findings Underscore Importance of Timing

Commenting on the study, Luis F. Lara, MD, division chief of digestive diseases at the University of Cincinnati, who co-moderated the session, agreed that evidence soundly supports early cholecystectomy.

“We also did a large study looking at this and there’s no doubt that doing it during the index admission has a tremendous effect on long-term outcomes,” Lara told GI & Hepatology News.

Lara noted that “part of it is people don’t show up again until they get sick again, so we don’t want to lose that opportunity the first time, during the index admission,” he said.

Lara’s previous studies have specifically documented how early cholecystectomy for acute biliary pancreatitis improves outcomes of hospitalization for cirrhosis and factors associated with early unplanned readmissions following same-admission cholecystectomy for acute biliary pancreatitis.

Akwi W. Asombang, MD, an interventional gastroenterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, both in Boston, agreed that the findings are important.

“We know that if a cholecystectomy is not performed in the same admission as ERCP, the stones in the gallbladder remain and may migrate out into the bile duct, resulting in further complications as described in the study,” Asombang, also a session co-moderator, told GI & Hepatology News.

She noted that the practice can vary between institutions based on factors including the availability of physicians to perform the cholecystectomy.

Potential complications in delaying the procedure can range from inflammation and pancreatitis to obstruction of the bile duct, “which then can result in cholangitis and eventually sepsis or even death,” Asombang cautioned.

“So the timing of the procedure with ERCP is definitely significant,” she said.

El Halabi and Asombang had no disclosures to report. Lara reported a relationship with AbbVie.

A version of this article first appeared on Medscape.com.

Patients with gallstone disease blocking the bile duct (choledochlithiasis) who do not have gall bladder removal in the same hospital admission as endoscopic retrograde pancreatography (ERCP) have as much as a 17-fold increase in the risk for biliary complications, regardless of the receipt of sphincterotomy or stenting, new research showed.

“These findings suggest an opportunity for systemic interventions, including prioritization algorithms and better perioperative coordination, to address preventable delays,” reported the authors in the study, presented at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

Choledocholithiasis can occur in up to 20% of symptomatic gallstone cases, and while guidelines recommend having a cholecystectomy concurrently with ERCP, data on the best timing is inconsistent and delays in gall bladder removal are consequently common.

One large study, for instance, the PONCHO trial conducted at 23 hospitals in Netherlands, showed complications to be significantly lower with same-admission vs interval cholecystectomy (4.7% vs 16.9%; P = .02).

Meanwhile, other research has suggested that delayed cholecystectomy is a preferred approach, allowing for removal when there is less inflammation.

Real world data meanwhile shows, despite the guidelines, the procedures are performed at the same time as ERCP only in about 41% of cases, first author Jessica El Halabi, MD, of the Johns Hopkins Hospital, Baltimore, said.

To further investigate outcomes associated with those delays, El Halabi and colleagues conducted a retrospective cohort study involving 507 patients admitted with choledocholithiasis at the hospital and community hospitals between 2005 and 2023 who had 12 months or more follow-up.

The patients had a mean age of 59 years and 59.4% were women.

Of the patients, 265 (52.3%) underwent early cholecystectomy, defined as surgery during the index admission, while 242 (47.7%) underwent delayed cholecystectomy, defined as postdischarge cholecystectomy or if cholecystectomy was not performed.

Overall, biliary complications occurred in as many as 23% of those who had delayed cholecystectomy compared with just 0.8% among those having the early cholecystectomy (P < .001).

Of patients who had delayed cholecystectomy and developed complications, 15.5% did so within 3 months, 6.5% by 6 months, and 1% by 12 months.

Among those who had ERCP with sphincterotomy, there were no significant differences in rates of biliary complications vs those who did not have sphincterotomy (26% vs 21%; P = .74), while stenting also did not reduce the risk (25% vs 27%; P = .81).

The leading reasons for delayed cholecystectomy included patients having a high surgical risk (27.3%), concurrent biliary pathology (19.2%), and physician preference (14%).

The findings underscore that “concurrent cholecystectomy is associated with the lowest risk of biliary complications,” El Halabi said.

“Delayed cholecystectomy is associated with an approximately 23% incidence of biliary complications with 1 year of initial admission, with the highest incidence occurring within 3 months,” she added. “Neither sphincterotomy nor stenting during ERCP mitigates this risk.”

“Early cholecystectomy during the index admission remains the most reliable strategy to reduce recurrent events.”

 

Findings Underscore Importance of Timing

Commenting on the study, Luis F. Lara, MD, division chief of digestive diseases at the University of Cincinnati, who co-moderated the session, agreed that evidence soundly supports early cholecystectomy.

“We also did a large study looking at this and there’s no doubt that doing it during the index admission has a tremendous effect on long-term outcomes,” Lara told GI & Hepatology News.

Lara noted that “part of it is people don’t show up again until they get sick again, so we don’t want to lose that opportunity the first time, during the index admission,” he said.

Lara’s previous studies have specifically documented how early cholecystectomy for acute biliary pancreatitis improves outcomes of hospitalization for cirrhosis and factors associated with early unplanned readmissions following same-admission cholecystectomy for acute biliary pancreatitis.

Akwi W. Asombang, MD, an interventional gastroenterologist at Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, both in Boston, agreed that the findings are important.

“We know that if a cholecystectomy is not performed in the same admission as ERCP, the stones in the gallbladder remain and may migrate out into the bile duct, resulting in further complications as described in the study,” Asombang, also a session co-moderator, told GI & Hepatology News.

She noted that the practice can vary between institutions based on factors including the availability of physicians to perform the cholecystectomy.

Potential complications in delaying the procedure can range from inflammation and pancreatitis to obstruction of the bile duct, “which then can result in cholangitis and eventually sepsis or even death,” Asombang cautioned.

“So the timing of the procedure with ERCP is definitely significant,” she said.

El Halabi and Asombang had no disclosures to report. Lara reported a relationship with AbbVie.

A version of this article first appeared on Medscape.com.

Introduction

The majority of patients in the United States are now overweight or obese, and as gastroenterologists we treat a number of conditions that are caused or worsened by obesity.¹ Cirrhosis related to metabolic associated fatty liver disease (MAFLD) is now a leading indication for liver transplantation in the US² and obesity is a clear risk factor for all major malignancies of the GI tract, including esophageal, gastric cardia, pancreatic, liver, gallbladder, colon, and rectum.³ Obesity is associated with dysbiosis and impacts barrier function: increasing permeability, abnormal gut bacterial translocation, and inflammation.⁴ It is more common than malnutrition in our patients with inflammatory bowel disease (IBD), where it impacts response to biologic drugs, increases the technical difficulty of surgeries, such as IPAA, and is associated with worse surgical outcomes.⁵ Furthermore, patients with obesity may be less likely to undergo preventative cancer screenings and are at increased risk related to sedation for endoscopic procedures.⁶ With over 40% of Americans suffering from obesity, and increasingly effective treatments available, the integration of weight management into a gastroenterology practice is essential to optimize outcomes.

Understanding the Mechanisms of Obesity

There are complex orexigenic and anorexigenic brain pathways in the hypothalamus which control global energy balance.⁷ Obesity results when energy intake exceeds energy expenditure. While overeating and a sedentary lifestyle are commonly blamed, there are a number of elements that contribute, including genetics, medical conditions, medications, psychosocial factors, and environmental components. For example, sleep loss contributes to weight gain by several mechanisms including increasing ghrelin and decreasing leptin levels, thereby increasing hunger and appetite, as well as by decreasing insulin sensitivity and increasing cortisol. Subjects exposed to sleep deprivation in research settings take in 550 kcal more the following day.⁸ Medications used commonly in GI practice including corticosteroids, antihistamines, propranolol, and amitriptyline, are obesogenic⁹ and cannabis can impact hypothalamic pathways to stimulate hunger.¹⁰

When patients diet or exercise to lose weight, as we have traditionally advised, there are strong hormonal changes and metabolic adaptations that occur to preserve the defended fat mass or “set point.” Loss of adipose tissue results in decreased production of leptin, a hormone that stimulates satiety pathways and inhibits orexigenic pathways, greatly increasing hunger and cravings. Increases in ghrelin production by the stomach decreases perceptions of fullness. With weight loss, energy requirements decrease, and muscles become more efficient, meaning fewer kcal are needed to maintain bodily processes.¹¹ Eventually a plateau is reached, while motivation to diet and restraint around food wane, and hedonistic (reward) pathways are activated. These powerful factors result in the regain of lost weight within one year in the majority of patients.

 

Implementing Weight Management into GI Practice

Given the stigma and bias around obesity, patients often feel shame and vulnerability around the condition. It is important to have empathy in your approach, asking permission to discuss weight and using patient-first language (e.g. “patient with obesity” not “obese patient”). While BMI is predictive of health outcomes, it does not measure body fat percentage and may be misleading, such as in muscular individuals. Other measures of adiposity including waist circumference and body composition testing, such as with DEXA, may provide additional data. A BMI of 30 or above defines obesity, though newer definitions incorporate related symptoms, organ disfunction, and metabolic abnormalities into the term “clinical obesity.”¹² Asian patients experience metabolic complications at a lower BMI, and therefore the definition of obese is 27.5kg/m2 in this population.

Begin by taking a weight history. Has this been a lifelong struggle or is there a particular life circumstance, such as working a third shift or recent pregnancy which precipitated weight gain? Patients should be asked about binge eating or eating late into the evening or waking at night to eat, as these disordered eating behaviors are managed with specific medications and behavioral therapies. Inquire about sleep duration and quality and refer for a sleep study if there is suspicion for obstructive sleep apnea. Other weight-related comorbidities including hyperlipidemia, type 2 diabetes mellitus (T2DM), and MAFLD should be considered and merit a more aggressive approach, as does more severe obesity (class III, BMI ≥40). Questions about marijuana and alcohol use as well as review of the medication list for obesogenic medications can provide further insight into modifiable contributing factors.

 

Pillars of Weight Management

The internet is awash with trendy diet recommendations, and widespread misconceptions about obesity management are even ingrained into how physicians approach the disease. It is critical to remember that this is not a consequence of bad choices or lack of self-control. Exercise alone is insufficient to result in significant weight loss.¹³ Furthermore, whether it is through low fat, low carb, or intermittent fasting, weight loss will occur with calorie deficit.¹⁴ Evidence-based diet and lifestyle recommendations to lay the groundwork for success should be discussed at each visit (see Table 1). The Mediterranean diet is recommended for weight loss as well as for several GI disorders (i.e., MAFLD and IBD) and is the optimal eating strategy for cardiovascular health.¹⁵ Patients should be advised to engage in 150 minutes of moderate exercise per week, such as brisk walking, and should incorporate resistance training to build muscle and maintain bone density.

Anti-obesity Medications

There are a number of medications, either FDA approved or used off label, for treatment of obesity (see Table 2).¹⁶ All are indicated for patients with a BMI of ≥ 30 kg/m2 or for those with a BMI between 27-29 kg/m2 with weight-related comorbidities and should be used in combination with diet and lifestyle interventions. None are approved or safe in pregnancy. Mechanisms of action vary by type and include decreased appetite, increased energy expenditure, improved insulin sensitivity, and interfere with absorption.

The newest and most effective anti-obesity medications (AOM), the glucagon-like peptide-1 receptor agonists (GLP-1 RA) are derived from gut hormones secreted in the distal small bowel and colon in response to a meal, which function to delay gastric emptying, increase insulin release from the pancreas, and reduce hepatic gluconeogenesis. Central nervous system effects are not yet entirely understood, but function to decrease appetite and increase satiety. Initially developed for treatment of T2DM, observed weight reduction in patients treated with GLP-1 RA led to clinical trials for treatment of obesity. Semaglutide treatment resulted in weight reduction of 16.9% of total body weight (TBW), and one third of subjects lost ≥ 20% of TBW.¹⁷ Tirzepatide combines GLP-1 RA and a gastric inhibitory polypeptide (GIP) receptor agonist, which also has an incretin effect and functions to slow gastric emptying. In the pivotal SURMOUNT trial, approximately 58% of patients achieved ≥20% loss of TBW¹⁸ with 15mg weekly dosing of tirzepatide. This class of drugs is a logical choice in patients with T2DM and obesity. Long-term treatment appears necessary, as patients typically regain two-thirds of lost weight within a year after GLP-1 RA are stopped.

Based on tumors observed in rodents, GLP-1 RA are contraindicated in patients with a personal or family history of multiple endocrine neoplasia type 2 (MEN II) or medullary thyroid cancer. These tumors have not been observed in humans treated with GLP-1 RA. They should be used with caution in patients with history of pancreatitis, gastroparesis, or diabetic retinopathy, though a recent systematic review and meta-analysis suggests showed little to no increased risk for biliary events from GLP-1 RA.¹⁹ Side effects are most commonly gastrointestinal in nature (nausea, reflux, constipation or diarrhea) and are typically most severe with initiation of the drug and with dose escalation. Side effects can be mitigated by initiating these drugs at lowest doses and gradually titrating up (every four weeks) based on effectiveness and tolerability. Antisecretory, antiemetic, and laxative medications can also be used to help manage GLP-1 RA related side effects.

There is no reason to escalate to highest doses if patients are experiencing weight loss and reduction in food cravings at lower doses. Both semaglutide and tirzepatide are administered subcutaneously every seven days. Once patients have reached goal weight, they can either continue maintenance therapy at that same dose/interval, or if motivated to do so, may gradually reduce the weekly dose in a stepwise approach to determine the minimally effective dose to maintain weight loss. There are not yet published maintenance studies to guide this process. Currently the price of GLP-1 RA and inconsistent insurance coverage make them inaccessible to many patients. The manufacturers of both semaglutide and tirzepatide offer direct to consumer pricing and home delivery.

 

Bariatric Surgery

In patients with higher BMI (≥35kg/m2) or those with BMI ≥30kg/m2 and obesity-related metabolic disease and the desire to avoid lifelong medications or who fail or are intolerant of AOM, bariatric options should be considered.²⁰ Sleeve gastrectomy has become the most performed surgery for treatment of obesity. It is a restrictive procedure, removing 80% of the stomach, but a drop in circulating levels of ghrelin afterwards also leads to decreased feelings of hunger. It results in weight loss of 25-30% TBW loss. It is not a good choice for patients who suffer from severe GERD, as this typically worsens afterwards; furthermore, de novo Barrett’s has been observed in nearly 6% of patients who undergo sleeve gastrectomy.²¹

Roux-en-Y gastric bypass is a restrictive and malabsorptive procedure, resulting in 30-35% TBW loss. It has beneficial and immediate metabolic effects, including increased release of endogenous GLP-1, which leads to improvements in weight-related T2DM. The newer single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) starts with a sleeve gastrectomy, making a smaller tube-shaped stomach. The duodenum is divided just after the stomach and then a loop of ileum is brought up and connected to the stomach (see Figure 1). This procedure is highly effective, with patients losing 75-95% of excess body weight and is becoming a preferred option for patients with greater BMI (≥50kg/m2). It is also an option for patients who have already had a sleeve gastrectomy and are seeking further weight loss. Because there is only one anastomosis, perioperative complications, such as anastomotic leaks, are reduced. The risk of micronutrient deficiencies is present with all malabsorptive procedures, and these patients must supplement with multivitamins, iron, vitamin D, and calcium. 

 

Endoscopic Therapies

Endoscopic bariatric and metabolic therapies (EBMTs) have been increasingly studied and utilized, and this less invasive option may be more appropriate for or attractive to many patients. Intragastric balloons, which reduce meal volume and delay gastric emptying, can be used short term only (six months) resulting in loss of about 6.9% of total body weight (TBW) greater than lifestyle modification (LM) alone, and may be considered in limited situations, such as need for pre-operative weight loss to reduce risks in very obese individuals.²²

Endoscopic gastric remodeling (EGR), also known as endoscopic sleeve gastrectomy (ESG), is a purely restrictive procedure in which the stomach is cinched to resize and reshape using an endoscopic suturing device (see Figure 2).²³ It is an option for patients with class 1 or 2 obesity, with data from a randomized controlled trial in this population demonstrating mean percentage of TBW loss of 13.6% at 52 weeks compared to 0.8% in those treated with LM alone.²⁴ A recent meta-analysis of 21 observational studies, including patients with higher BMIs (32.5 to 49.9 kg/m2) showed pooled average weight loss of 17.3% TBW at 12 months with EGR.²² This procedure has potential advantages of fewer complications, quicker recovery, and much less new-onset GERD compared to laparoscopic sleeve gastrectomy. Furthermore, it may be utilized in combination with AOMs to achieve optimum weight loss and metabolic outcomes.^25,26 Potential adverse events include abdominal pain, nausea and vomiting (which may be severe), as well as rare instances of intra/extra luminal bleeding or abdominal abscess requiring drainage.²²

Recent joint American/European Gastrointestinal Endoscopy guidelines suggest the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity.²² Small bowel interventions including duodenal-jejunal bypass liner and duodenal mucosal resurfacing are being investigated for patients with obesity and type 2 diabetes but not yet commercially available.

 

Conclusion

Given the overlap of obesity with many GI disorders, it is entirely appropriate for gastroenterologists to consider it worthy of aggressive treatment, particularly in patients with MAFLD and other serious weight related comorbidities. With a compassionate and empathetic approach, and a number of highly effective medical, endoscopic, and surgical therapies now available, weight management has the potential to be extremely rewarding when implemented in GI practice.

Dr. Kelly is based in the Department of Medicine, Division of Gastroenterology, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston, Massachusetts. She serves on the clinical advisory board for OpenBiome (unpaid) and has served on an advisory board for Eli Lilly and Company.

References

1. Hales CM, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020 Feb:(360):1–8.

2. Pais R, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016 Dec. doi: 10.1016/j.jhep.2016.07.033.

3. Lauby-Secretan B, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug. doi: 10.1056/NEJMsr1606602.

4. Kim A. Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. J Clin Gastroenterol. 2015 Nov-Dec. doi: 10.1097/MCG.0000000000000356.

5. Singh S, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb. doi: 10.1038/nrgastro.2016.181.

6. Sundararaman L, Goudra B. Sedation for GI Endoscopy in the Morbidly Obese: Challenges and Possible Solutions. J Clin Med. 2024 Aug. doi: 10.3390/jcm13164635.

7. Bombassaro B, et al. The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments. Arch Endocrinol Metab. 2024 Nov. doi: 10.20945/2359-4292-2024-0082.

8. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care. 2011 Jul. doi: 10.1097/MCO.0b013e3283479109.

9. Desalermos A, et al. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). 2019 May. doi: 10.1002/oby.22444.

10. Lord MN, Noble EE. Hypothalamic cannabinoid signaling: Consequences for eating behavior. Pharmacol Res Perspect. 2024 Oct. doi: 10.1002/prp2.1251.

11. Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/.

12. Rubino F, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025 Mar. doi: 10.1016/S2213-8587(24)00316-4.

13. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017 Aug. doi: 10.2337/ds17-0013.

14. Chaput JP, et al. Widespread misconceptions about obesity. Can Fam Physician. 2014 Nov. PMID: 25392431.

15. Muscogiuri G, et al. Mediterranean Diet and Obesity-related Disorders: What is the Evidence? Curr Obes Rep. 2022 Dec. doi: 10.1007/s13679-022-00481-1.

16. Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024 Aug. doi: 10.1001/jama.2024.10816.

17. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb. doi: 10.1056/NEJMoa2032183.

18. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun. doi: 10.1056/NEJMoa2206038.

19. Chiang CH, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.003.

20. Aderinto N, et al. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg (Lond). 2023 Nov. doi: 10.1097/MS9.0000000000001472.

21. Chandan S, et al. Risk of De Novo Barrett’s Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan. doi: 10.1016/j.cgh.2024.06.041.

22. Jirapinyo P, et al. American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity. Gastrointest Endosc. 2024 Jun. doi: 10.1016/j.gie.2023.12.004.

23. Nduma BN, et al. Endoscopic Gastric Sleeve: A Review of Literature. Cureus. 2023 Mar. doi: 10.7759/cureus.36353.

24. Abu Dayyeh BK, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug. doi: 10.1016/S0140-6736(22)01280-6.

25. Gala K, et al. Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings. Obes Pillars. 2024 May. doi: 10.1016/j.obpill.2024.100112.

26. Chung CS, et al. Endoscopic sleeve gastroplasty combined with anti-obesity medication for better control of weight and diabetes. Clin Endosc. 2025 May. doi: 10.5946/ce.2024.274.

Introduction

The majority of patients in the United States are now overweight or obese, and as gastroenterologists we treat a number of conditions that are caused or worsened by obesity.¹ Cirrhosis related to metabolic associated fatty liver disease (MAFLD) is now a leading indication for liver transplantation in the US² and obesity is a clear risk factor for all major malignancies of the GI tract, including esophageal, gastric cardia, pancreatic, liver, gallbladder, colon, and rectum.³ Obesity is associated with dysbiosis and impacts barrier function: increasing permeability, abnormal gut bacterial translocation, and inflammation.⁴ It is more common than malnutrition in our patients with inflammatory bowel disease (IBD), where it impacts response to biologic drugs, increases the technical difficulty of surgeries, such as IPAA, and is associated with worse surgical outcomes.⁵ Furthermore, patients with obesity may be less likely to undergo preventative cancer screenings and are at increased risk related to sedation for endoscopic procedures.⁶ With over 40% of Americans suffering from obesity, and increasingly effective treatments available, the integration of weight management into a gastroenterology practice is essential to optimize outcomes.

Understanding the Mechanisms of Obesity

There are complex orexigenic and anorexigenic brain pathways in the hypothalamus which control global energy balance.⁷ Obesity results when energy intake exceeds energy expenditure. While overeating and a sedentary lifestyle are commonly blamed, there are a number of elements that contribute, including genetics, medical conditions, medications, psychosocial factors, and environmental components. For example, sleep loss contributes to weight gain by several mechanisms including increasing ghrelin and decreasing leptin levels, thereby increasing hunger and appetite, as well as by decreasing insulin sensitivity and increasing cortisol. Subjects exposed to sleep deprivation in research settings take in 550 kcal more the following day.⁸ Medications used commonly in GI practice including corticosteroids, antihistamines, propranolol, and amitriptyline, are obesogenic⁹ and cannabis can impact hypothalamic pathways to stimulate hunger.¹⁰

When patients diet or exercise to lose weight, as we have traditionally advised, there are strong hormonal changes and metabolic adaptations that occur to preserve the defended fat mass or “set point.” Loss of adipose tissue results in decreased production of leptin, a hormone that stimulates satiety pathways and inhibits orexigenic pathways, greatly increasing hunger and cravings. Increases in ghrelin production by the stomach decreases perceptions of fullness. With weight loss, energy requirements decrease, and muscles become more efficient, meaning fewer kcal are needed to maintain bodily processes.¹¹ Eventually a plateau is reached, while motivation to diet and restraint around food wane, and hedonistic (reward) pathways are activated. These powerful factors result in the regain of lost weight within one year in the majority of patients.

 

Implementing Weight Management into GI Practice

Given the stigma and bias around obesity, patients often feel shame and vulnerability around the condition. It is important to have empathy in your approach, asking permission to discuss weight and using patient-first language (e.g. “patient with obesity” not “obese patient”). While BMI is predictive of health outcomes, it does not measure body fat percentage and may be misleading, such as in muscular individuals. Other measures of adiposity including waist circumference and body composition testing, such as with DEXA, may provide additional data. A BMI of 30 or above defines obesity, though newer definitions incorporate related symptoms, organ disfunction, and metabolic abnormalities into the term “clinical obesity.”¹² Asian patients experience metabolic complications at a lower BMI, and therefore the definition of obese is 27.5kg/m2 in this population.

Begin by taking a weight history. Has this been a lifelong struggle or is there a particular life circumstance, such as working a third shift or recent pregnancy which precipitated weight gain? Patients should be asked about binge eating or eating late into the evening or waking at night to eat, as these disordered eating behaviors are managed with specific medications and behavioral therapies. Inquire about sleep duration and quality and refer for a sleep study if there is suspicion for obstructive sleep apnea. Other weight-related comorbidities including hyperlipidemia, type 2 diabetes mellitus (T2DM), and MAFLD should be considered and merit a more aggressive approach, as does more severe obesity (class III, BMI ≥40). Questions about marijuana and alcohol use as well as review of the medication list for obesogenic medications can provide further insight into modifiable contributing factors.

 

Pillars of Weight Management

The internet is awash with trendy diet recommendations, and widespread misconceptions about obesity management are even ingrained into how physicians approach the disease. It is critical to remember that this is not a consequence of bad choices or lack of self-control. Exercise alone is insufficient to result in significant weight loss.¹³ Furthermore, whether it is through low fat, low carb, or intermittent fasting, weight loss will occur with calorie deficit.¹⁴ Evidence-based diet and lifestyle recommendations to lay the groundwork for success should be discussed at each visit (see Table 1). The Mediterranean diet is recommended for weight loss as well as for several GI disorders (i.e., MAFLD and IBD) and is the optimal eating strategy for cardiovascular health.¹⁵ Patients should be advised to engage in 150 minutes of moderate exercise per week, such as brisk walking, and should incorporate resistance training to build muscle and maintain bone density.

Anti-obesity Medications

There are a number of medications, either FDA approved or used off label, for treatment of obesity (see Table 2).¹⁶ All are indicated for patients with a BMI of ≥ 30 kg/m2 or for those with a BMI between 27-29 kg/m2 with weight-related comorbidities and should be used in combination with diet and lifestyle interventions. None are approved or safe in pregnancy. Mechanisms of action vary by type and include decreased appetite, increased energy expenditure, improved insulin sensitivity, and interfere with absorption.

The newest and most effective anti-obesity medications (AOM), the glucagon-like peptide-1 receptor agonists (GLP-1 RA) are derived from gut hormones secreted in the distal small bowel and colon in response to a meal, which function to delay gastric emptying, increase insulin release from the pancreas, and reduce hepatic gluconeogenesis. Central nervous system effects are not yet entirely understood, but function to decrease appetite and increase satiety. Initially developed for treatment of T2DM, observed weight reduction in patients treated with GLP-1 RA led to clinical trials for treatment of obesity. Semaglutide treatment resulted in weight reduction of 16.9% of total body weight (TBW), and one third of subjects lost ≥ 20% of TBW.¹⁷ Tirzepatide combines GLP-1 RA and a gastric inhibitory polypeptide (GIP) receptor agonist, which also has an incretin effect and functions to slow gastric emptying. In the pivotal SURMOUNT trial, approximately 58% of patients achieved ≥20% loss of TBW¹⁸ with 15mg weekly dosing of tirzepatide. This class of drugs is a logical choice in patients with T2DM and obesity. Long-term treatment appears necessary, as patients typically regain two-thirds of lost weight within a year after GLP-1 RA are stopped.

Based on tumors observed in rodents, GLP-1 RA are contraindicated in patients with a personal or family history of multiple endocrine neoplasia type 2 (MEN II) or medullary thyroid cancer. These tumors have not been observed in humans treated with GLP-1 RA. They should be used with caution in patients with history of pancreatitis, gastroparesis, or diabetic retinopathy, though a recent systematic review and meta-analysis suggests showed little to no increased risk for biliary events from GLP-1 RA.¹⁹ Side effects are most commonly gastrointestinal in nature (nausea, reflux, constipation or diarrhea) and are typically most severe with initiation of the drug and with dose escalation. Side effects can be mitigated by initiating these drugs at lowest doses and gradually titrating up (every four weeks) based on effectiveness and tolerability. Antisecretory, antiemetic, and laxative medications can also be used to help manage GLP-1 RA related side effects.

There is no reason to escalate to highest doses if patients are experiencing weight loss and reduction in food cravings at lower doses. Both semaglutide and tirzepatide are administered subcutaneously every seven days. Once patients have reached goal weight, they can either continue maintenance therapy at that same dose/interval, or if motivated to do so, may gradually reduce the weekly dose in a stepwise approach to determine the minimally effective dose to maintain weight loss. There are not yet published maintenance studies to guide this process. Currently the price of GLP-1 RA and inconsistent insurance coverage make them inaccessible to many patients. The manufacturers of both semaglutide and tirzepatide offer direct to consumer pricing and home delivery.

 

Bariatric Surgery

In patients with higher BMI (≥35kg/m2) or those with BMI ≥30kg/m2 and obesity-related metabolic disease and the desire to avoid lifelong medications or who fail or are intolerant of AOM, bariatric options should be considered.²⁰ Sleeve gastrectomy has become the most performed surgery for treatment of obesity. It is a restrictive procedure, removing 80% of the stomach, but a drop in circulating levels of ghrelin afterwards also leads to decreased feelings of hunger. It results in weight loss of 25-30% TBW loss. It is not a good choice for patients who suffer from severe GERD, as this typically worsens afterwards; furthermore, de novo Barrett’s has been observed in nearly 6% of patients who undergo sleeve gastrectomy.²¹

Roux-en-Y gastric bypass is a restrictive and malabsorptive procedure, resulting in 30-35% TBW loss. It has beneficial and immediate metabolic effects, including increased release of endogenous GLP-1, which leads to improvements in weight-related T2DM. The newer single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) starts with a sleeve gastrectomy, making a smaller tube-shaped stomach. The duodenum is divided just after the stomach and then a loop of ileum is brought up and connected to the stomach (see Figure 1). This procedure is highly effective, with patients losing 75-95% of excess body weight and is becoming a preferred option for patients with greater BMI (≥50kg/m2). It is also an option for patients who have already had a sleeve gastrectomy and are seeking further weight loss. Because there is only one anastomosis, perioperative complications, such as anastomotic leaks, are reduced. The risk of micronutrient deficiencies is present with all malabsorptive procedures, and these patients must supplement with multivitamins, iron, vitamin D, and calcium. 

 

Endoscopic Therapies

Endoscopic bariatric and metabolic therapies (EBMTs) have been increasingly studied and utilized, and this less invasive option may be more appropriate for or attractive to many patients. Intragastric balloons, which reduce meal volume and delay gastric emptying, can be used short term only (six months) resulting in loss of about 6.9% of total body weight (TBW) greater than lifestyle modification (LM) alone, and may be considered in limited situations, such as need for pre-operative weight loss to reduce risks in very obese individuals.²²

Endoscopic gastric remodeling (EGR), also known as endoscopic sleeve gastrectomy (ESG), is a purely restrictive procedure in which the stomach is cinched to resize and reshape using an endoscopic suturing device (see Figure 2).²³ It is an option for patients with class 1 or 2 obesity, with data from a randomized controlled trial in this population demonstrating mean percentage of TBW loss of 13.6% at 52 weeks compared to 0.8% in those treated with LM alone.²⁴ A recent meta-analysis of 21 observational studies, including patients with higher BMIs (32.5 to 49.9 kg/m2) showed pooled average weight loss of 17.3% TBW at 12 months with EGR.²² This procedure has potential advantages of fewer complications, quicker recovery, and much less new-onset GERD compared to laparoscopic sleeve gastrectomy. Furthermore, it may be utilized in combination with AOMs to achieve optimum weight loss and metabolic outcomes.^25,26 Potential adverse events include abdominal pain, nausea and vomiting (which may be severe), as well as rare instances of intra/extra luminal bleeding or abdominal abscess requiring drainage.²²

Recent joint American/European Gastrointestinal Endoscopy guidelines suggest the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity.²² Small bowel interventions including duodenal-jejunal bypass liner and duodenal mucosal resurfacing are being investigated for patients with obesity and type 2 diabetes but not yet commercially available.

 

Conclusion

Given the overlap of obesity with many GI disorders, it is entirely appropriate for gastroenterologists to consider it worthy of aggressive treatment, particularly in patients with MAFLD and other serious weight related comorbidities. With a compassionate and empathetic approach, and a number of highly effective medical, endoscopic, and surgical therapies now available, weight management has the potential to be extremely rewarding when implemented in GI practice.

Dr. Kelly is based in the Department of Medicine, Division of Gastroenterology, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston, Massachusetts. She serves on the clinical advisory board for OpenBiome (unpaid) and has served on an advisory board for Eli Lilly and Company.

References

1. Hales CM, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020 Feb:(360):1–8.

2. Pais R, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016 Dec. doi: 10.1016/j.jhep.2016.07.033.

3. Lauby-Secretan B, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug. doi: 10.1056/NEJMsr1606602.

4. Kim A. Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. J Clin Gastroenterol. 2015 Nov-Dec. doi: 10.1097/MCG.0000000000000356.

5. Singh S, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb. doi: 10.1038/nrgastro.2016.181.

6. Sundararaman L, Goudra B. Sedation for GI Endoscopy in the Morbidly Obese: Challenges and Possible Solutions. J Clin Med. 2024 Aug. doi: 10.3390/jcm13164635.

7. Bombassaro B, et al. The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments. Arch Endocrinol Metab. 2024 Nov. doi: 10.20945/2359-4292-2024-0082.

8. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care. 2011 Jul. doi: 10.1097/MCO.0b013e3283479109.

9. Desalermos A, et al. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). 2019 May. doi: 10.1002/oby.22444.

10. Lord MN, Noble EE. Hypothalamic cannabinoid signaling: Consequences for eating behavior. Pharmacol Res Perspect. 2024 Oct. doi: 10.1002/prp2.1251.

11. Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/.

12. Rubino F, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025 Mar. doi: 10.1016/S2213-8587(24)00316-4.

13. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017 Aug. doi: 10.2337/ds17-0013.

14. Chaput JP, et al. Widespread misconceptions about obesity. Can Fam Physician. 2014 Nov. PMID: 25392431.

15. Muscogiuri G, et al. Mediterranean Diet and Obesity-related Disorders: What is the Evidence? Curr Obes Rep. 2022 Dec. doi: 10.1007/s13679-022-00481-1.

16. Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024 Aug. doi: 10.1001/jama.2024.10816.

17. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb. doi: 10.1056/NEJMoa2032183.

18. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun. doi: 10.1056/NEJMoa2206038.

19. Chiang CH, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.003.

20. Aderinto N, et al. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg (Lond). 2023 Nov. doi: 10.1097/MS9.0000000000001472.

21. Chandan S, et al. Risk of De Novo Barrett’s Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan. doi: 10.1016/j.cgh.2024.06.041.

22. Jirapinyo P, et al. American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity. Gastrointest Endosc. 2024 Jun. doi: 10.1016/j.gie.2023.12.004.

23. Nduma BN, et al. Endoscopic Gastric Sleeve: A Review of Literature. Cureus. 2023 Mar. doi: 10.7759/cureus.36353.

24. Abu Dayyeh BK, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug. doi: 10.1016/S0140-6736(22)01280-6.

25. Gala K, et al. Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings. Obes Pillars. 2024 May. doi: 10.1016/j.obpill.2024.100112.

26. Chung CS, et al. Endoscopic sleeve gastroplasty combined with anti-obesity medication for better control of weight and diabetes. Clin Endosc. 2025 May. doi: 10.5946/ce.2024.274.

Introduction

The majority of patients in the United States are now overweight or obese, and as gastroenterologists we treat a number of conditions that are caused or worsened by obesity.¹ Cirrhosis related to metabolic associated fatty liver disease (MAFLD) is now a leading indication for liver transplantation in the US² and obesity is a clear risk factor for all major malignancies of the GI tract, including esophageal, gastric cardia, pancreatic, liver, gallbladder, colon, and rectum.³ Obesity is associated with dysbiosis and impacts barrier function: increasing permeability, abnormal gut bacterial translocation, and inflammation.⁴ It is more common than malnutrition in our patients with inflammatory bowel disease (IBD), where it impacts response to biologic drugs, increases the technical difficulty of surgeries, such as IPAA, and is associated with worse surgical outcomes.⁵ Furthermore, patients with obesity may be less likely to undergo preventative cancer screenings and are at increased risk related to sedation for endoscopic procedures.⁶ With over 40% of Americans suffering from obesity, and increasingly effective treatments available, the integration of weight management into a gastroenterology practice is essential to optimize outcomes.

Understanding the Mechanisms of Obesity

There are complex orexigenic and anorexigenic brain pathways in the hypothalamus which control global energy balance.⁷ Obesity results when energy intake exceeds energy expenditure. While overeating and a sedentary lifestyle are commonly blamed, there are a number of elements that contribute, including genetics, medical conditions, medications, psychosocial factors, and environmental components. For example, sleep loss contributes to weight gain by several mechanisms including increasing ghrelin and decreasing leptin levels, thereby increasing hunger and appetite, as well as by decreasing insulin sensitivity and increasing cortisol. Subjects exposed to sleep deprivation in research settings take in 550 kcal more the following day.⁸ Medications used commonly in GI practice including corticosteroids, antihistamines, propranolol, and amitriptyline, are obesogenic⁹ and cannabis can impact hypothalamic pathways to stimulate hunger.¹⁰

When patients diet or exercise to lose weight, as we have traditionally advised, there are strong hormonal changes and metabolic adaptations that occur to preserve the defended fat mass or “set point.” Loss of adipose tissue results in decreased production of leptin, a hormone that stimulates satiety pathways and inhibits orexigenic pathways, greatly increasing hunger and cravings. Increases in ghrelin production by the stomach decreases perceptions of fullness. With weight loss, energy requirements decrease, and muscles become more efficient, meaning fewer kcal are needed to maintain bodily processes.¹¹ Eventually a plateau is reached, while motivation to diet and restraint around food wane, and hedonistic (reward) pathways are activated. These powerful factors result in the regain of lost weight within one year in the majority of patients.

 

Implementing Weight Management into GI Practice

Given the stigma and bias around obesity, patients often feel shame and vulnerability around the condition. It is important to have empathy in your approach, asking permission to discuss weight and using patient-first language (e.g. “patient with obesity” not “obese patient”). While BMI is predictive of health outcomes, it does not measure body fat percentage and may be misleading, such as in muscular individuals. Other measures of adiposity including waist circumference and body composition testing, such as with DEXA, may provide additional data. A BMI of 30 or above defines obesity, though newer definitions incorporate related symptoms, organ disfunction, and metabolic abnormalities into the term “clinical obesity.”¹² Asian patients experience metabolic complications at a lower BMI, and therefore the definition of obese is 27.5kg/m2 in this population.

Begin by taking a weight history. Has this been a lifelong struggle or is there a particular life circumstance, such as working a third shift or recent pregnancy which precipitated weight gain? Patients should be asked about binge eating or eating late into the evening or waking at night to eat, as these disordered eating behaviors are managed with specific medications and behavioral therapies. Inquire about sleep duration and quality and refer for a sleep study if there is suspicion for obstructive sleep apnea. Other weight-related comorbidities including hyperlipidemia, type 2 diabetes mellitus (T2DM), and MAFLD should be considered and merit a more aggressive approach, as does more severe obesity (class III, BMI ≥40). Questions about marijuana and alcohol use as well as review of the medication list for obesogenic medications can provide further insight into modifiable contributing factors.

 

Pillars of Weight Management

The internet is awash with trendy diet recommendations, and widespread misconceptions about obesity management are even ingrained into how physicians approach the disease. It is critical to remember that this is not a consequence of bad choices or lack of self-control. Exercise alone is insufficient to result in significant weight loss.¹³ Furthermore, whether it is through low fat, low carb, or intermittent fasting, weight loss will occur with calorie deficit.¹⁴ Evidence-based diet and lifestyle recommendations to lay the groundwork for success should be discussed at each visit (see Table 1). The Mediterranean diet is recommended for weight loss as well as for several GI disorders (i.e., MAFLD and IBD) and is the optimal eating strategy for cardiovascular health.¹⁵ Patients should be advised to engage in 150 minutes of moderate exercise per week, such as brisk walking, and should incorporate resistance training to build muscle and maintain bone density.

Anti-obesity Medications

There are a number of medications, either FDA approved or used off label, for treatment of obesity (see Table 2).¹⁶ All are indicated for patients with a BMI of ≥ 30 kg/m2 or for those with a BMI between 27-29 kg/m2 with weight-related comorbidities and should be used in combination with diet and lifestyle interventions. None are approved or safe in pregnancy. Mechanisms of action vary by type and include decreased appetite, increased energy expenditure, improved insulin sensitivity, and interfere with absorption.

The newest and most effective anti-obesity medications (AOM), the glucagon-like peptide-1 receptor agonists (GLP-1 RA) are derived from gut hormones secreted in the distal small bowel and colon in response to a meal, which function to delay gastric emptying, increase insulin release from the pancreas, and reduce hepatic gluconeogenesis. Central nervous system effects are not yet entirely understood, but function to decrease appetite and increase satiety. Initially developed for treatment of T2DM, observed weight reduction in patients treated with GLP-1 RA led to clinical trials for treatment of obesity. Semaglutide treatment resulted in weight reduction of 16.9% of total body weight (TBW), and one third of subjects lost ≥ 20% of TBW.¹⁷ Tirzepatide combines GLP-1 RA and a gastric inhibitory polypeptide (GIP) receptor agonist, which also has an incretin effect and functions to slow gastric emptying. In the pivotal SURMOUNT trial, approximately 58% of patients achieved ≥20% loss of TBW¹⁸ with 15mg weekly dosing of tirzepatide. This class of drugs is a logical choice in patients with T2DM and obesity. Long-term treatment appears necessary, as patients typically regain two-thirds of lost weight within a year after GLP-1 RA are stopped.

Based on tumors observed in rodents, GLP-1 RA are contraindicated in patients with a personal or family history of multiple endocrine neoplasia type 2 (MEN II) or medullary thyroid cancer. These tumors have not been observed in humans treated with GLP-1 RA. They should be used with caution in patients with history of pancreatitis, gastroparesis, or diabetic retinopathy, though a recent systematic review and meta-analysis suggests showed little to no increased risk for biliary events from GLP-1 RA.¹⁹ Side effects are most commonly gastrointestinal in nature (nausea, reflux, constipation or diarrhea) and are typically most severe with initiation of the drug and with dose escalation. Side effects can be mitigated by initiating these drugs at lowest doses and gradually titrating up (every four weeks) based on effectiveness and tolerability. Antisecretory, antiemetic, and laxative medications can also be used to help manage GLP-1 RA related side effects.

There is no reason to escalate to highest doses if patients are experiencing weight loss and reduction in food cravings at lower doses. Both semaglutide and tirzepatide are administered subcutaneously every seven days. Once patients have reached goal weight, they can either continue maintenance therapy at that same dose/interval, or if motivated to do so, may gradually reduce the weekly dose in a stepwise approach to determine the minimally effective dose to maintain weight loss. There are not yet published maintenance studies to guide this process. Currently the price of GLP-1 RA and inconsistent insurance coverage make them inaccessible to many patients. The manufacturers of both semaglutide and tirzepatide offer direct to consumer pricing and home delivery.

 

Bariatric Surgery

In patients with higher BMI (≥35kg/m2) or those with BMI ≥30kg/m2 and obesity-related metabolic disease and the desire to avoid lifelong medications or who fail or are intolerant of AOM, bariatric options should be considered.²⁰ Sleeve gastrectomy has become the most performed surgery for treatment of obesity. It is a restrictive procedure, removing 80% of the stomach, but a drop in circulating levels of ghrelin afterwards also leads to decreased feelings of hunger. It results in weight loss of 25-30% TBW loss. It is not a good choice for patients who suffer from severe GERD, as this typically worsens afterwards; furthermore, de novo Barrett’s has been observed in nearly 6% of patients who undergo sleeve gastrectomy.²¹

Roux-en-Y gastric bypass is a restrictive and malabsorptive procedure, resulting in 30-35% TBW loss. It has beneficial and immediate metabolic effects, including increased release of endogenous GLP-1, which leads to improvements in weight-related T2DM. The newer single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) starts with a sleeve gastrectomy, making a smaller tube-shaped stomach. The duodenum is divided just after the stomach and then a loop of ileum is brought up and connected to the stomach (see Figure 1). This procedure is highly effective, with patients losing 75-95% of excess body weight and is becoming a preferred option for patients with greater BMI (≥50kg/m2). It is also an option for patients who have already had a sleeve gastrectomy and are seeking further weight loss. Because there is only one anastomosis, perioperative complications, such as anastomotic leaks, are reduced. The risk of micronutrient deficiencies is present with all malabsorptive procedures, and these patients must supplement with multivitamins, iron, vitamin D, and calcium. 

 

Endoscopic Therapies

Endoscopic bariatric and metabolic therapies (EBMTs) have been increasingly studied and utilized, and this less invasive option may be more appropriate for or attractive to many patients. Intragastric balloons, which reduce meal volume and delay gastric emptying, can be used short term only (six months) resulting in loss of about 6.9% of total body weight (TBW) greater than lifestyle modification (LM) alone, and may be considered in limited situations, such as need for pre-operative weight loss to reduce risks in very obese individuals.²²

Endoscopic gastric remodeling (EGR), also known as endoscopic sleeve gastrectomy (ESG), is a purely restrictive procedure in which the stomach is cinched to resize and reshape using an endoscopic suturing device (see Figure 2).²³ It is an option for patients with class 1 or 2 obesity, with data from a randomized controlled trial in this population demonstrating mean percentage of TBW loss of 13.6% at 52 weeks compared to 0.8% in those treated with LM alone.²⁴ A recent meta-analysis of 21 observational studies, including patients with higher BMIs (32.5 to 49.9 kg/m2) showed pooled average weight loss of 17.3% TBW at 12 months with EGR.²² This procedure has potential advantages of fewer complications, quicker recovery, and much less new-onset GERD compared to laparoscopic sleeve gastrectomy. Furthermore, it may be utilized in combination with AOMs to achieve optimum weight loss and metabolic outcomes.^25,26 Potential adverse events include abdominal pain, nausea and vomiting (which may be severe), as well as rare instances of intra/extra luminal bleeding or abdominal abscess requiring drainage.²²

Recent joint American/European Gastrointestinal Endoscopy guidelines suggest the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity.²² Small bowel interventions including duodenal-jejunal bypass liner and duodenal mucosal resurfacing are being investigated for patients with obesity and type 2 diabetes but not yet commercially available.

 

Conclusion

Given the overlap of obesity with many GI disorders, it is entirely appropriate for gastroenterologists to consider it worthy of aggressive treatment, particularly in patients with MAFLD and other serious weight related comorbidities. With a compassionate and empathetic approach, and a number of highly effective medical, endoscopic, and surgical therapies now available, weight management has the potential to be extremely rewarding when implemented in GI practice.

Dr. Kelly is based in the Department of Medicine, Division of Gastroenterology, Brigham and Women’s Hospital, and Harvard Medical School, both in Boston, Massachusetts. She serves on the clinical advisory board for OpenBiome (unpaid) and has served on an advisory board for Eli Lilly and Company.

References

1. Hales CM, et al. Prevalence of Obesity and Severe Obesity Among Adults: United States, 2017-2018. NCHS Data Brief 2020 Feb:(360):1–8.

2. Pais R, et al. NAFLD and liver transplantation: Current burden and expected challenges. J Hepatol. 2016 Dec. doi: 10.1016/j.jhep.2016.07.033.

3. Lauby-Secretan B, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med. 2016 Aug. doi: 10.1056/NEJMsr1606602.

4. Kim A. Dysbiosis: A Review Highlighting Obesity and Inflammatory Bowel Disease. J Clin Gastroenterol. 2015 Nov-Dec. doi: 10.1097/MCG.0000000000000356.

5. Singh S, et al. Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes. Nat Rev Gastroenterol Hepatol. 2017 Feb. doi: 10.1038/nrgastro.2016.181.

6. Sundararaman L, Goudra B. Sedation for GI Endoscopy in the Morbidly Obese: Challenges and Possible Solutions. J Clin Med. 2024 Aug. doi: 10.3390/jcm13164635.

7. Bombassaro B, et al. The hypothalamus as the central regulator of energy balance and its impact on current and future obesity treatments. Arch Endocrinol Metab. 2024 Nov. doi: 10.20945/2359-4292-2024-0082.

8. Beccuti G, Pannain S. Sleep and obesity. Curr Opin Clin Nutr Metab Care. 2011 Jul. doi: 10.1097/MCO.0b013e3283479109.

9. Desalermos A, et al. Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program. Obesity (Silver Spring). 2019 May. doi: 10.1002/oby.22444.

10. Lord MN, Noble EE. Hypothalamic cannabinoid signaling: Consequences for eating behavior. Pharmacol Res Perspect. 2024 Oct. doi: 10.1002/prp2.1251.

11. Farhana A, Rehman A. Metabolic Consequences of Weight Reduction. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572145/.

12. Rubino F, et al. Definition and diagnostic criteria of clinical obesity. Lancet Diabetes Endocrinol. 2025 Mar. doi: 10.1016/S2213-8587(24)00316-4.

13. Cox CE. Role of Physical Activity for Weight Loss and Weight Maintenance. Diabetes Spectr. 2017 Aug. doi: 10.2337/ds17-0013.

14. Chaput JP, et al. Widespread misconceptions about obesity. Can Fam Physician. 2014 Nov. PMID: 25392431.

15. Muscogiuri G, et al. Mediterranean Diet and Obesity-related Disorders: What is the Evidence? Curr Obes Rep. 2022 Dec. doi: 10.1007/s13679-022-00481-1.

16. Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024 Aug. doi: 10.1001/jama.2024.10816.

17. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Feb. doi: 10.1056/NEJMoa2032183.

18. Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jun. doi: 10.1056/NEJMoa2206038.

19. Chiang CH, et al. Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis. Gastroenterology. 2025 Nov. doi: 10.1053/j.gastro.2025.06.003.

20. Aderinto N, et al. Recent advances in bariatric surgery: a narrative review of weight loss procedures. Ann Med Surg (Lond). 2023 Nov. doi: 10.1097/MS9.0000000000001472.

21. Chandan S, et al. Risk of De Novo Barrett’s Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan. doi: 10.1016/j.cgh.2024.06.041.

22. Jirapinyo P, et al. American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity. Gastrointest Endosc. 2024 Jun. doi: 10.1016/j.gie.2023.12.004.

23. Nduma BN, et al. Endoscopic Gastric Sleeve: A Review of Literature. Cureus. 2023 Mar. doi: 10.7759/cureus.36353.

24. Abu Dayyeh BK, et al. Endoscopic sleeve gastroplasty for treatment of class 1 and 2 obesity (MERIT): a prospective, multicentre, randomised trial. Lancet. 2022 Aug. doi: 10.1016/S0140-6736(22)01280-6.

25. Gala K, et al. Outcomes of concomitant antiobesity medication use with endoscopic sleeve gastroplasty in clinical US settings. Obes Pillars. 2024 May. doi: 10.1016/j.obpill.2024.100112.

26. Chung CS, et al. Endoscopic sleeve gastroplasty combined with anti-obesity medication for better control of weight and diabetes. Clin Endosc. 2025 May. doi: 10.5946/ce.2024.274.

Discussion

A diagnosis of lichen sclerosus (LS) was made based on clinical and dermoscopic features, followed by confirmation with histology. The patient’s presentation included typical signs and symptoms of LS: itching, burning, intermittent bleeding, perianal hemorrhage, fusion of the clitoral head, and fissures. Other presentations can include dyspareunia, erosions, and excoriations; however, these symptoms and signs were not reported or seen in this patient.

LS typically affects the anogenital region and has 2 peak incidences: in preadolescent teens and during the fifth to sixth decade of life.¹ This patient presented with a case of extragenital LS, which is less common than the classic presentation of LS that affects the genitals. This variant’s epidemiology differs, as it is less common in children and more common in postmenopausal women.² Extragenital LS presents as white, atrophic plaques with a predilection for sites including the trunk, breasts, upper arms, and sites of physical trauma, with symptoms of dryness and pruritus. Over time, the papules can coalesce and form ivory, scar-like papules or plaques with a wrinkled surface. In advanced stages, telangiectasia or follicular plugging can be present, along with flattening of the dermal-epidermal junction. This flat interface is fragile and can result in bullae that may become hemorrhagic.

Cutaneous squamous cell carcinoma (SCC) may infrequently arise from LS, similar to other chronic inflammatory dermatoses.³ Lichen planus is typically not associated with an increased risk of SCC, except in the oral and hypertrophic variants. However, LS may be considered a premalignant process, and many vulvar SCC cases are noted to have adjacent LS lesions.³

Autoimmune and genetic factors contribute to the pathogenesis of LS. Extracellular matrix protein 1 (ECM1) binds molecules of the basement membrane zone and dermis, contributing to the structure and integrity of skin. Autoantibodies against ECM1 and other antigens of the basement membrane zone, including BP180 and BP320, were found in LS.² HLA-DQ7 major histocompatibility complex class II antigens have been associated with LS.¹

On histologic examination, the epidermis of LS is atrophic with hyperkeratosis. The dermis shows homogenization and sclerosis of superficial collagen with a band-like lymphocytic infiltrate below the sclerosis. The basal layer is thickened, showing basal cell vacuolization and hydropic degeneration.⁴

First-line treatment for genital and extragenital variants of LS is high-potency topical steroids for 3 months or until the skin texture and color resolve (ie, clobetasol 0.05% cream or ointment). The second-line treatment is a topical calcineurin inhibitor. These treatments are used for management. They are not cures for LS, as relapse is possible after the initial treatment course is completed. Adverse effects of high potency topical steroids are skin burning, skin atrophy, and fragility, telangiectasia. The adverse effects of topical calcineurin inhibitors are stinging and burning on application.

Other Diagnostic Considerations

Inverse psoriasis (IP) is a variant of psoriasis that presents as erythematous, well-demarcated plaques with minimal scale in intertriginous areas and flexural surfaces. Localized dermatophyte, candidal, or bacterial infections can trigger IP.⁵ It occurs in about 3% to 7% of patients with plaque psoriasis and is thought to form due to koebnerization via mechanical friction of flexural zones.⁶ The patient described in this case did not have IP because IP would be more likely to present as a well-demarcated erythematous plaque rather than a patch.

Histologically, IP shows regular psoriasiform acanthosis and hypogranulosis of the epidermis, Munro microabscess, spongiform pustules of Kogoj, dilated tortuous dermal vessels, and thinning of the suprapapillary plates.⁵

Lichen planus pigmentosus-inversus (LPPI) is also known as lichen planus pigmentosus—intertriginous variant. This variant of lichen planus pigmentosus presents as multiple gray to dark brown macules and patches with poorly defined borders in a linear distribution limited to intertriginous areas, flexural surfaces, or following the lines of Blaschko.⁷ About 20% of cases present with frontal fibrosing alopecia. It is most common in individuals with intermediate and darker skin pigmentation, has a higher prevalence in females, and typically occurs within the third and fifth decades of life. Friction is a common trigger of LPPI.⁷ A diagnosis of LPPI is incorrect because the lesions would present as gray to dark brown macules, as opposed to the shiny white atrophic thin papules with surrounding pink and purple patches seen in this case.

Histologically, while both LS and LPPI share band-like lymphocytic infiltrate and basal cell vacuolization, findings in the dermis differ. LPPI shows melanophages and prominent melanin incontinence, while LS shows homogenization and sclerosis of superficial collagen.^1,8 LPPI also shows absence of compensatory keratinocyte proliferation.

Morphea is an inflammatory disease that affects the dermis and subcutaneous fat, resulting in sclerosis that appears scarlike. Its prevalence increases with age and has a 4:1 prevalence in females, with the plaque type being the most common variant. ⁹ The typical presentation of plaque-type morphea is an insidious onset of asymptomatic, slightly elevated, erythematous or violaceous, slightly edematous plaques with centrifugal expansion. The center of the plaque may become sclerotic and indurated, acquiring a shiny white color with a peripheral “lilac” ring. Trunk and upper extremity involvement is common. Morphea is associated with increased antisingle-stranded DNA, antitopoisomerase IIa, antiphospholipid, antifibrillin-1, and antihistone antibodies. Triggers of morphea are believed to be localized insults to the skin, including mechanical trauma, injections, vaccinations, and irradiation.⁹ This answer is incorrect because the patient’s lesions were pruritic and had genital involvement, which are not typical of morphea. Morphea can be differentiated with based on symptoms (lack of pruritus, pain, burning), morphology of lesions (induration versus atrophy), dermoscopy (fibrotic beams with less scale and hemorrhage vs keratotic follicular plugs), and histopathology (depth of inflammation in superficial and deep dermis).

Histology of morphea can differ based on the stage, whether the lesion is sampled in the inflammatory margin or central sclerosis, and the depth of affected skin. At the inflammatory margin, vascular changes, including endothelial swelling and edema, are present, as well as CD4+ T cells, eosinophils, plasma cells, and mast cells surrounding smaller blood vessels. In late stages, the inflammatory infiltrate is no longer present, the epidermis appears regular, and there is a flattened dermal-epidermal junction. Distinct features include homogenous collagen bundles that replace many dermal structures, with atrophic eccrine glands that appear “trapped” in the thickened dermis, and homogenized and hyalinized subcutis.⁹

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and presents as annular, erythematous or hypopigmented patches and plaques with fine scale and tumors on the buttocks and sun-protected areas of the limbs and trunk. Lesions can appear with prominent poikiloderma or atrophic or lichenified skin.¹⁰ It is most common in males of African descent aged 50 to 55 years. The etiology is largely unknown but believed to be multifactorial. This answer is incorrect because the lesions in this patient appeared more atrophic, were less well demarcated, and lacked the scale that would be present in MF.

On histology, both LS and MF show band-like lymphocytic infiltrate, however MF lacks the homogenization and sclerosis of superficial collagen that is present in the dermis of LS. Also, MF demonstrates epidermotropism of atypical lymphocytes forming Pautrier microabscess.¹⁰

Primary Care Role

Primary care physicians can diagnose and treat LS. Referral to dermatology is not mandatory. Note that topical steroids can be used daily for up to 12 weeks. In LS, early treatment is associated with improved outcomes and minimizes the risk of irreversible skin changes.¹¹ Follow-up during the treatment period is recommended to monitor subjective and objective response to treatment. Follow-up after the initial treatment is recommended since LS is typically chronic, can relapse, and SCC can infrequently arise from LS lesions.¹¹

Discussion

A diagnosis of lichen sclerosus (LS) was made based on clinical and dermoscopic features, followed by confirmation with histology. The patient’s presentation included typical signs and symptoms of LS: itching, burning, intermittent bleeding, perianal hemorrhage, fusion of the clitoral head, and fissures. Other presentations can include dyspareunia, erosions, and excoriations; however, these symptoms and signs were not reported or seen in this patient.

LS typically affects the anogenital region and has 2 peak incidences: in preadolescent teens and during the fifth to sixth decade of life.¹ This patient presented with a case of extragenital LS, which is less common than the classic presentation of LS that affects the genitals. This variant’s epidemiology differs, as it is less common in children and more common in postmenopausal women.² Extragenital LS presents as white, atrophic plaques with a predilection for sites including the trunk, breasts, upper arms, and sites of physical trauma, with symptoms of dryness and pruritus. Over time, the papules can coalesce and form ivory, scar-like papules or plaques with a wrinkled surface. In advanced stages, telangiectasia or follicular plugging can be present, along with flattening of the dermal-epidermal junction. This flat interface is fragile and can result in bullae that may become hemorrhagic.

Cutaneous squamous cell carcinoma (SCC) may infrequently arise from LS, similar to other chronic inflammatory dermatoses.³ Lichen planus is typically not associated with an increased risk of SCC, except in the oral and hypertrophic variants. However, LS may be considered a premalignant process, and many vulvar SCC cases are noted to have adjacent LS lesions.³

Autoimmune and genetic factors contribute to the pathogenesis of LS. Extracellular matrix protein 1 (ECM1) binds molecules of the basement membrane zone and dermis, contributing to the structure and integrity of skin. Autoantibodies against ECM1 and other antigens of the basement membrane zone, including BP180 and BP320, were found in LS.² HLA-DQ7 major histocompatibility complex class II antigens have been associated with LS.¹

On histologic examination, the epidermis of LS is atrophic with hyperkeratosis. The dermis shows homogenization and sclerosis of superficial collagen with a band-like lymphocytic infiltrate below the sclerosis. The basal layer is thickened, showing basal cell vacuolization and hydropic degeneration.⁴

First-line treatment for genital and extragenital variants of LS is high-potency topical steroids for 3 months or until the skin texture and color resolve (ie, clobetasol 0.05% cream or ointment). The second-line treatment is a topical calcineurin inhibitor. These treatments are used for management. They are not cures for LS, as relapse is possible after the initial treatment course is completed. Adverse effects of high potency topical steroids are skin burning, skin atrophy, and fragility, telangiectasia. The adverse effects of topical calcineurin inhibitors are stinging and burning on application.

Other Diagnostic Considerations

Inverse psoriasis (IP) is a variant of psoriasis that presents as erythematous, well-demarcated plaques with minimal scale in intertriginous areas and flexural surfaces. Localized dermatophyte, candidal, or bacterial infections can trigger IP.⁵ It occurs in about 3% to 7% of patients with plaque psoriasis and is thought to form due to koebnerization via mechanical friction of flexural zones.⁶ The patient described in this case did not have IP because IP would be more likely to present as a well-demarcated erythematous plaque rather than a patch.

Histologically, IP shows regular psoriasiform acanthosis and hypogranulosis of the epidermis, Munro microabscess, spongiform pustules of Kogoj, dilated tortuous dermal vessels, and thinning of the suprapapillary plates.⁵

Lichen planus pigmentosus-inversus (LPPI) is also known as lichen planus pigmentosus—intertriginous variant. This variant of lichen planus pigmentosus presents as multiple gray to dark brown macules and patches with poorly defined borders in a linear distribution limited to intertriginous areas, flexural surfaces, or following the lines of Blaschko.⁷ About 20% of cases present with frontal fibrosing alopecia. It is most common in individuals with intermediate and darker skin pigmentation, has a higher prevalence in females, and typically occurs within the third and fifth decades of life. Friction is a common trigger of LPPI.⁷ A diagnosis of LPPI is incorrect because the lesions would present as gray to dark brown macules, as opposed to the shiny white atrophic thin papules with surrounding pink and purple patches seen in this case.

Histologically, while both LS and LPPI share band-like lymphocytic infiltrate and basal cell vacuolization, findings in the dermis differ. LPPI shows melanophages and prominent melanin incontinence, while LS shows homogenization and sclerosis of superficial collagen.^1,8 LPPI also shows absence of compensatory keratinocyte proliferation.

Morphea is an inflammatory disease that affects the dermis and subcutaneous fat, resulting in sclerosis that appears scarlike. Its prevalence increases with age and has a 4:1 prevalence in females, with the plaque type being the most common variant. ⁹ The typical presentation of plaque-type morphea is an insidious onset of asymptomatic, slightly elevated, erythematous or violaceous, slightly edematous plaques with centrifugal expansion. The center of the plaque may become sclerotic and indurated, acquiring a shiny white color with a peripheral “lilac” ring. Trunk and upper extremity involvement is common. Morphea is associated with increased antisingle-stranded DNA, antitopoisomerase IIa, antiphospholipid, antifibrillin-1, and antihistone antibodies. Triggers of morphea are believed to be localized insults to the skin, including mechanical trauma, injections, vaccinations, and irradiation.⁹ This answer is incorrect because the patient’s lesions were pruritic and had genital involvement, which are not typical of morphea. Morphea can be differentiated with based on symptoms (lack of pruritus, pain, burning), morphology of lesions (induration versus atrophy), dermoscopy (fibrotic beams with less scale and hemorrhage vs keratotic follicular plugs), and histopathology (depth of inflammation in superficial and deep dermis).

Histology of morphea can differ based on the stage, whether the lesion is sampled in the inflammatory margin or central sclerosis, and the depth of affected skin. At the inflammatory margin, vascular changes, including endothelial swelling and edema, are present, as well as CD4+ T cells, eosinophils, plasma cells, and mast cells surrounding smaller blood vessels. In late stages, the inflammatory infiltrate is no longer present, the epidermis appears regular, and there is a flattened dermal-epidermal junction. Distinct features include homogenous collagen bundles that replace many dermal structures, with atrophic eccrine glands that appear “trapped” in the thickened dermis, and homogenized and hyalinized subcutis.⁹

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and presents as annular, erythematous or hypopigmented patches and plaques with fine scale and tumors on the buttocks and sun-protected areas of the limbs and trunk. Lesions can appear with prominent poikiloderma or atrophic or lichenified skin.¹⁰ It is most common in males of African descent aged 50 to 55 years. The etiology is largely unknown but believed to be multifactorial. This answer is incorrect because the lesions in this patient appeared more atrophic, were less well demarcated, and lacked the scale that would be present in MF.

On histology, both LS and MF show band-like lymphocytic infiltrate, however MF lacks the homogenization and sclerosis of superficial collagen that is present in the dermis of LS. Also, MF demonstrates epidermotropism of atypical lymphocytes forming Pautrier microabscess.¹⁰

Primary Care Role

Primary care physicians can diagnose and treat LS. Referral to dermatology is not mandatory. Note that topical steroids can be used daily for up to 12 weeks. In LS, early treatment is associated with improved outcomes and minimizes the risk of irreversible skin changes.¹¹ Follow-up during the treatment period is recommended to monitor subjective and objective response to treatment. Follow-up after the initial treatment is recommended since LS is typically chronic, can relapse, and SCC can infrequently arise from LS lesions.¹¹

Discussion

A diagnosis of lichen sclerosus (LS) was made based on clinical and dermoscopic features, followed by confirmation with histology. The patient’s presentation included typical signs and symptoms of LS: itching, burning, intermittent bleeding, perianal hemorrhage, fusion of the clitoral head, and fissures. Other presentations can include dyspareunia, erosions, and excoriations; however, these symptoms and signs were not reported or seen in this patient.

LS typically affects the anogenital region and has 2 peak incidences: in preadolescent teens and during the fifth to sixth decade of life.¹ This patient presented with a case of extragenital LS, which is less common than the classic presentation of LS that affects the genitals. This variant’s epidemiology differs, as it is less common in children and more common in postmenopausal women.² Extragenital LS presents as white, atrophic plaques with a predilection for sites including the trunk, breasts, upper arms, and sites of physical trauma, with symptoms of dryness and pruritus. Over time, the papules can coalesce and form ivory, scar-like papules or plaques with a wrinkled surface. In advanced stages, telangiectasia or follicular plugging can be present, along with flattening of the dermal-epidermal junction. This flat interface is fragile and can result in bullae that may become hemorrhagic.

Cutaneous squamous cell carcinoma (SCC) may infrequently arise from LS, similar to other chronic inflammatory dermatoses.³ Lichen planus is typically not associated with an increased risk of SCC, except in the oral and hypertrophic variants. However, LS may be considered a premalignant process, and many vulvar SCC cases are noted to have adjacent LS lesions.³

Autoimmune and genetic factors contribute to the pathogenesis of LS. Extracellular matrix protein 1 (ECM1) binds molecules of the basement membrane zone and dermis, contributing to the structure and integrity of skin. Autoantibodies against ECM1 and other antigens of the basement membrane zone, including BP180 and BP320, were found in LS.² HLA-DQ7 major histocompatibility complex class II antigens have been associated with LS.¹

On histologic examination, the epidermis of LS is atrophic with hyperkeratosis. The dermis shows homogenization and sclerosis of superficial collagen with a band-like lymphocytic infiltrate below the sclerosis. The basal layer is thickened, showing basal cell vacuolization and hydropic degeneration.⁴

First-line treatment for genital and extragenital variants of LS is high-potency topical steroids for 3 months or until the skin texture and color resolve (ie, clobetasol 0.05% cream or ointment). The second-line treatment is a topical calcineurin inhibitor. These treatments are used for management. They are not cures for LS, as relapse is possible after the initial treatment course is completed. Adverse effects of high potency topical steroids are skin burning, skin atrophy, and fragility, telangiectasia. The adverse effects of topical calcineurin inhibitors are stinging and burning on application.

Other Diagnostic Considerations

Inverse psoriasis (IP) is a variant of psoriasis that presents as erythematous, well-demarcated plaques with minimal scale in intertriginous areas and flexural surfaces. Localized dermatophyte, candidal, or bacterial infections can trigger IP.⁵ It occurs in about 3% to 7% of patients with plaque psoriasis and is thought to form due to koebnerization via mechanical friction of flexural zones.⁶ The patient described in this case did not have IP because IP would be more likely to present as a well-demarcated erythematous plaque rather than a patch.

Histologically, IP shows regular psoriasiform acanthosis and hypogranulosis of the epidermis, Munro microabscess, spongiform pustules of Kogoj, dilated tortuous dermal vessels, and thinning of the suprapapillary plates.⁵

Lichen planus pigmentosus-inversus (LPPI) is also known as lichen planus pigmentosus—intertriginous variant. This variant of lichen planus pigmentosus presents as multiple gray to dark brown macules and patches with poorly defined borders in a linear distribution limited to intertriginous areas, flexural surfaces, or following the lines of Blaschko.⁷ About 20% of cases present with frontal fibrosing alopecia. It is most common in individuals with intermediate and darker skin pigmentation, has a higher prevalence in females, and typically occurs within the third and fifth decades of life. Friction is a common trigger of LPPI.⁷ A diagnosis of LPPI is incorrect because the lesions would present as gray to dark brown macules, as opposed to the shiny white atrophic thin papules with surrounding pink and purple patches seen in this case.

Histologically, while both LS and LPPI share band-like lymphocytic infiltrate and basal cell vacuolization, findings in the dermis differ. LPPI shows melanophages and prominent melanin incontinence, while LS shows homogenization and sclerosis of superficial collagen.^1,8 LPPI also shows absence of compensatory keratinocyte proliferation.

Morphea is an inflammatory disease that affects the dermis and subcutaneous fat, resulting in sclerosis that appears scarlike. Its prevalence increases with age and has a 4:1 prevalence in females, with the plaque type being the most common variant. ⁹ The typical presentation of plaque-type morphea is an insidious onset of asymptomatic, slightly elevated, erythematous or violaceous, slightly edematous plaques with centrifugal expansion. The center of the plaque may become sclerotic and indurated, acquiring a shiny white color with a peripheral “lilac” ring. Trunk and upper extremity involvement is common. Morphea is associated with increased antisingle-stranded DNA, antitopoisomerase IIa, antiphospholipid, antifibrillin-1, and antihistone antibodies. Triggers of morphea are believed to be localized insults to the skin, including mechanical trauma, injections, vaccinations, and irradiation.⁹ This answer is incorrect because the patient’s lesions were pruritic and had genital involvement, which are not typical of morphea. Morphea can be differentiated with based on symptoms (lack of pruritus, pain, burning), morphology of lesions (induration versus atrophy), dermoscopy (fibrotic beams with less scale and hemorrhage vs keratotic follicular plugs), and histopathology (depth of inflammation in superficial and deep dermis).

Histology of morphea can differ based on the stage, whether the lesion is sampled in the inflammatory margin or central sclerosis, and the depth of affected skin. At the inflammatory margin, vascular changes, including endothelial swelling and edema, are present, as well as CD4+ T cells, eosinophils, plasma cells, and mast cells surrounding smaller blood vessels. In late stages, the inflammatory infiltrate is no longer present, the epidermis appears regular, and there is a flattened dermal-epidermal junction. Distinct features include homogenous collagen bundles that replace many dermal structures, with atrophic eccrine glands that appear “trapped” in the thickened dermis, and homogenized and hyalinized subcutis.⁹

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma and presents as annular, erythematous or hypopigmented patches and plaques with fine scale and tumors on the buttocks and sun-protected areas of the limbs and trunk. Lesions can appear with prominent poikiloderma or atrophic or lichenified skin.¹⁰ It is most common in males of African descent aged 50 to 55 years. The etiology is largely unknown but believed to be multifactorial. This answer is incorrect because the lesions in this patient appeared more atrophic, were less well demarcated, and lacked the scale that would be present in MF.

On histology, both LS and MF show band-like lymphocytic infiltrate, however MF lacks the homogenization and sclerosis of superficial collagen that is present in the dermis of LS. Also, MF demonstrates epidermotropism of atypical lymphocytes forming Pautrier microabscess.¹⁰

Primary Care Role

Primary care physicians can diagnose and treat LS. Referral to dermatology is not mandatory. Note that topical steroids can be used daily for up to 12 weeks. In LS, early treatment is associated with improved outcomes and minimizes the risk of irreversible skin changes.¹¹ Follow-up during the treatment period is recommended to monitor subjective and objective response to treatment. Follow-up after the initial treatment is recommended since LS is typically chronic, can relapse, and SCC can infrequently arise from LS lesions.¹¹

PHOENIX — The oral medication resmetirom significantly improved liver stiffness and reduced portal hypertension in metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis, according to the results of a new study.

As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.

Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.

According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.

In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.

Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.

At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.

After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.

Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.

Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.

 

Changing the Treatment Landscape for MASH-Related Cirrhosis

When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”

Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.

A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.

“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.

“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.

Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.

A version of this article appeared on Medscape.com.

PHOENIX — The oral medication resmetirom significantly improved liver stiffness and reduced portal hypertension in metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis, according to the results of a new study.

As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.

Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.

According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.

In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.

Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.

At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.

After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.

Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.

Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.

 

Changing the Treatment Landscape for MASH-Related Cirrhosis

When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”

Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.

A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.

“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.

“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.

Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.

A version of this article appeared on Medscape.com.

PHOENIX — The oral medication resmetirom significantly improved liver stiffness and reduced portal hypertension in metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis, according to the results of a new study.

As well as showing sustained reduction in liver stiffness on vibration-controlled transient elastography (VCTE) after 2 years of treatment with resmetirom, the study suggested that up to 35% of patients could “potentially reverse their cirrhosis,” said lead author Naim Alkhouri, MD, chief medical officer and director of the steatotic liver program at Arizona Liver Health in Phoenix.

Alkhouri presented data on patients with compensated cirrhosis from a 1-year open-label extension of the already-completed MAESTRO-NAFLD-1 study at American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

The FDA approved resmetirom (Rezdiffra, Madrigal Pharmaceuticals) in 2024 for MASH and moderate-to-advanced liver fibrosis (consistent with stage F2 and F3 disease), to be used in conjunction with diet and exercise. The agency granted the once-daily, oral thyroid hormone receptor beta-selective agonist breakthrough therapy designation and priority review.

According to the American Liver Foundation, about 5% of adults in the US have MASH — one of the leading causes of liver transplantation in the country. There is currently no FDA-approved therapy for compensated cirrhosis caused by MASH, said Alkhouri. Patients with MASH cirrhosis with clinically significant portal hypertension (CSPH) experience major adverse liver outcomes.

In an analysis of 122 patients with Child Pugh A MASH cirrhosis who completed both a year in an open-label arm of MAESTRO-NAFLD-1 and a 1-year extension, 113 (93%) completed 2 years of treatment with resmetirom (80 mg). Of the 122 patients, only 114 received MRI proton density fat fraction (MRI-PDFF) testing — 93 (82%) had a baseline of > 5% indicating cirrhosis, while 21 (18%) had an MRI-PDFF of < 5%.

Patients were assessed for baseline portal hypertension (Baveno VII) with FibroScan VCTE and platelet count, which was confirmed using magnetic resonance elastography (MRE). Noninvasive biomarkers and imaging were analyzed at baseline and out to 2 years.

At baseline, 63% of patients were categorized as probable/definitive CSPH (Baveno VII). At 1 year of treatment with resmetirom, 20% of patients who were CSPH positive no longer met the criteria, and at 2 years this number had increased to 28%.

After 2 years of treatment, more than half of the patients had a sustained reduction in liver stiffness of more than 25%, as measured by VCTE; and 35% of patients with confirmed F4 at baseline (liver biopsy F4 and/or platelets < 140/MRE ≥ 5 with VCTE ≥ 15) had a conversion to F3.

Patients taking resmetirom also had significant improvements in MRI-PDFF and MRE at 2 years. Almost a third of those with a baseline MRI-PDFF > 5% improved, while 43% of those with a baseline of < 5% improved.

Although 113 patients had an adverse event — primarily gastrointestinal — the observed events were consistent with previous studies. Twenty-seven patients had a serious adverse event, but none were related to the study drug, said Alkhouri. The researchers reported that only 8% of patients discontinued the medication.

 

Changing the Treatment Landscape for MASH-Related Cirrhosis

When asked to comment by GI & Hepatology News, Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, said that “reversal of cirrhosis from F4 to F3 and reduction of portal hypertension are quite surprising, since cirrhosis typically progresses slowly.”

Ayesh said it was notable that the researchers had used imaging to confirm both functional and hemodynamic improvements in liver architecture not just biochemical changes. Given the results, “clinicians may reasonably consider off-label use in selected compensated patients until more outcome data become available,” he said.

A phase 3 study is underway to examine those outcomes, MAESTRO-NASH OUTCOMES, with 845 patients with MASH cirrhosis, and should be completed in 2027.

“Resmetirom could change the treatment landscape for MASH-related cirrhosis,” said Ayesh, adding, “this drug offers a chance to target the disease process itself,” while other therapies focus on preventing complications.

“For patients without access to liver transplant, a therapy that can slow or reverse disease progression could be transformative,” he told GI & Hepatology News.

Alkhouri disclosed that he is a consultant and speaker for Madrigal Pharmaceuticals. Three coauthors are Madrigal employees and own stock options in the company. Two coauthors are Madrigal consultants and advisers. Ayesh reported no conflicts.

A version of this article appeared on Medscape.com.

PHOENIX — Patients with or without polyp removal in an index colonoscopy commonly receive follow-up surveillance with a fecal immunochemical test (FIT), yet many of these patients do not receive a recommended colonoscopy after a positive FIT.

“In this large US study, we found interval FITs are frequently performed in patients with and without prior polypectomy,” said first author Natalie J. Wilson, MD, of the University of Minnesota in Minneapolis, while presenting the findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

“These findings reinforce the importance of colonoscopy following positive interval FIT, given the high risk of advanced neoplasia and colorectal cancer, regardless of polypectomy history,” Wilson said.

Guideline recommendations stress the need for follow-up surveillance with a colonoscopy, particularly in patients who have had a prior polypectomy, because of the higher risk.

Reasons patients may instead turn to FIT may include cost or other factors, she said.

To determine just how often that happens, how having a previous polypectomy affects FIT results, and how adherent patients are to follow up if a FIT result is positive, Wilson and her colleagues evaluated data from nearly 4.8 million individuals in the Veterans Health Administration Corporate Data Warehouse who underwent colonoscopy between 2000 and 2024.

Of the patients, 10.9% were found to have subsequently received interval FIT within 10 years of the index colonoscopy, and of those patients, nearly half (49.9%) had received a polypectomy at the index colonoscopy.

The average time from the colonoscopy/polypectomy to the interval FIT was 5.9 years (5.6 years in the polypectomy group vs 6.2 years in the non-polypectomy group).

Among the FIT screenings, results were positive in 17.2% of post-polypectomy patients and 14.1% of patients with no prior polypectomy, indicating a history of polypectomy to be predictive of a positive interval FIT (odds ratio [OR], 1.12; P < .0001).

Notably, while a follow-up colonoscopy is considered essential following a positive FIT result — and having a previous polypectomy should add further urgency to the matter — the study showed only 50.4% of those who had an earlier polypectomy went on to receive the recommended follow-up colonoscopy after a positive follow-up FIT, and the rate was 49.3% among those who had not received a polypectomy (P = .001).

For those who did receive a follow-up colonoscopy after a positive FIT, the duration of time to receiving the colonoscopy was longer among those who had a prior polypectomy, at 2.9 months compared with 2.5 months in the non-polypectomy group (P < .001).

Colonoscopy results following a positive FIT showed higher rates of detections among patients who had prior polypectomies than among those with no prior polypectomy, including tubular adenomas (54.7% vs 45.8%), tubulovillous adenomas (5.6% vs 4.7%), adenomas with high-grade dysplasia (0.8% vs 0.7%), sessile serrated lesions (3.52% vs 2.4%), advanced colorectal neoplasia (9.2% vs 7.9%), and colorectal cancer (3.3% vs 3.0%).

However, a prior polypectomy was not independently predictive of colorectal cancer (OR, 0.96; P = .65) or advanced colorectal neoplasia (OR, 0.97; P = .57) in the post-colonoscopy interval FIT.

The findings underscore that “positive results carried a high risk of advanced neoplasia or cancer, irrespective of prior polypectomy history,” Wilson said.

 

Clinicians Must ‘Do a Better Job’

Commenting on the study, William D. Chey, MD, AGAF, chief of the Division of Gastroenterology & Hepatology at the University of Michigan in Ann Arbor, noted that the study “addresses one of the biggest challenges we face as a profession, which is making sure that patients who have a positive stool test get a colonoscopy.”

He noted that the low rate of just 50% of recipients of positive FITs going on to receive a colonoscopy is consistent with what is observed in other trials.

“Other data suggests that the rate might even be significantly higher — at 70%-80%, depending upon the population and the test,” Chey told Medscape Medical News.

Reasons for the failure to receive the follow-up testing range from income restrictions (due to the high cost of a colonoscopy, especially if not covered by insurance), education, speaking a foreign language, and other factors, he said.

The relatively high rates of colon cancers detected by FIT in the study, in those with and without a prior polypectomy, along with findings from other studies “should raise questions about whether there might be a role for FIT testing in addition to colonoscopy.” However, much stronger evidence would be needed, Chey noted.

In the meantime, a key issue is “how do we do a better job of making sure that individuals who have a positive FIT test get a colonoscopy,” he said.

“I think a lot of this is going to come down to how it’s done at the primary care level.”

Chey added that in that, and any other setting, “the main message that needs to get out to people who are undergoing stool-based screening is that the stool test is only the first part of the screening process, and if it’s positive, a follow-up colonoscopy must be performed.”

“Otherwise, the stool-based test is of no value.”

Wilson had no disclosures to report. Chey’s disclosures included consulting and/or other relationships with Ardelyx, Atmo, Biomerica, Commonwealth Diagnostics International, Corprata, Dieta, Evinature, Food Marble, Gemelli, Kiwi BioScience, Modify Health, Nestlé, Phathom, Redhill, Salix/Valeant, Takeda, and Vibrant.

 

A version of this article appeared on Medscape.com . 

PHOENIX — Patients with or without polyp removal in an index colonoscopy commonly receive follow-up surveillance with a fecal immunochemical test (FIT), yet many of these patients do not receive a recommended colonoscopy after a positive FIT.

“In this large US study, we found interval FITs are frequently performed in patients with and without prior polypectomy,” said first author Natalie J. Wilson, MD, of the University of Minnesota in Minneapolis, while presenting the findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

“These findings reinforce the importance of colonoscopy following positive interval FIT, given the high risk of advanced neoplasia and colorectal cancer, regardless of polypectomy history,” Wilson said.

Guideline recommendations stress the need for follow-up surveillance with a colonoscopy, particularly in patients who have had a prior polypectomy, because of the higher risk.

Reasons patients may instead turn to FIT may include cost or other factors, she said.

To determine just how often that happens, how having a previous polypectomy affects FIT results, and how adherent patients are to follow up if a FIT result is positive, Wilson and her colleagues evaluated data from nearly 4.8 million individuals in the Veterans Health Administration Corporate Data Warehouse who underwent colonoscopy between 2000 and 2024.

Of the patients, 10.9% were found to have subsequently received interval FIT within 10 years of the index colonoscopy, and of those patients, nearly half (49.9%) had received a polypectomy at the index colonoscopy.

The average time from the colonoscopy/polypectomy to the interval FIT was 5.9 years (5.6 years in the polypectomy group vs 6.2 years in the non-polypectomy group).

Among the FIT screenings, results were positive in 17.2% of post-polypectomy patients and 14.1% of patients with no prior polypectomy, indicating a history of polypectomy to be predictive of a positive interval FIT (odds ratio [OR], 1.12; P < .0001).

Notably, while a follow-up colonoscopy is considered essential following a positive FIT result — and having a previous polypectomy should add further urgency to the matter — the study showed only 50.4% of those who had an earlier polypectomy went on to receive the recommended follow-up colonoscopy after a positive follow-up FIT, and the rate was 49.3% among those who had not received a polypectomy (P = .001).

For those who did receive a follow-up colonoscopy after a positive FIT, the duration of time to receiving the colonoscopy was longer among those who had a prior polypectomy, at 2.9 months compared with 2.5 months in the non-polypectomy group (P < .001).

Colonoscopy results following a positive FIT showed higher rates of detections among patients who had prior polypectomies than among those with no prior polypectomy, including tubular adenomas (54.7% vs 45.8%), tubulovillous adenomas (5.6% vs 4.7%), adenomas with high-grade dysplasia (0.8% vs 0.7%), sessile serrated lesions (3.52% vs 2.4%), advanced colorectal neoplasia (9.2% vs 7.9%), and colorectal cancer (3.3% vs 3.0%).

However, a prior polypectomy was not independently predictive of colorectal cancer (OR, 0.96; P = .65) or advanced colorectal neoplasia (OR, 0.97; P = .57) in the post-colonoscopy interval FIT.

The findings underscore that “positive results carried a high risk of advanced neoplasia or cancer, irrespective of prior polypectomy history,” Wilson said.

 

Clinicians Must ‘Do a Better Job’

Commenting on the study, William D. Chey, MD, AGAF, chief of the Division of Gastroenterology & Hepatology at the University of Michigan in Ann Arbor, noted that the study “addresses one of the biggest challenges we face as a profession, which is making sure that patients who have a positive stool test get a colonoscopy.”

He noted that the low rate of just 50% of recipients of positive FITs going on to receive a colonoscopy is consistent with what is observed in other trials.

“Other data suggests that the rate might even be significantly higher — at 70%-80%, depending upon the population and the test,” Chey told Medscape Medical News.

Reasons for the failure to receive the follow-up testing range from income restrictions (due to the high cost of a colonoscopy, especially if not covered by insurance), education, speaking a foreign language, and other factors, he said.

The relatively high rates of colon cancers detected by FIT in the study, in those with and without a prior polypectomy, along with findings from other studies “should raise questions about whether there might be a role for FIT testing in addition to colonoscopy.” However, much stronger evidence would be needed, Chey noted.

In the meantime, a key issue is “how do we do a better job of making sure that individuals who have a positive FIT test get a colonoscopy,” he said.

“I think a lot of this is going to come down to how it’s done at the primary care level.”

Chey added that in that, and any other setting, “the main message that needs to get out to people who are undergoing stool-based screening is that the stool test is only the first part of the screening process, and if it’s positive, a follow-up colonoscopy must be performed.”

“Otherwise, the stool-based test is of no value.”

Wilson had no disclosures to report. Chey’s disclosures included consulting and/or other relationships with Ardelyx, Atmo, Biomerica, Commonwealth Diagnostics International, Corprata, Dieta, Evinature, Food Marble, Gemelli, Kiwi BioScience, Modify Health, Nestlé, Phathom, Redhill, Salix/Valeant, Takeda, and Vibrant.

 

A version of this article appeared on Medscape.com . 

PHOENIX — Patients with or without polyp removal in an index colonoscopy commonly receive follow-up surveillance with a fecal immunochemical test (FIT), yet many of these patients do not receive a recommended colonoscopy after a positive FIT.

“In this large US study, we found interval FITs are frequently performed in patients with and without prior polypectomy,” said first author Natalie J. Wilson, MD, of the University of Minnesota in Minneapolis, while presenting the findings at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting.

“These findings reinforce the importance of colonoscopy following positive interval FIT, given the high risk of advanced neoplasia and colorectal cancer, regardless of polypectomy history,” Wilson said.

Guideline recommendations stress the need for follow-up surveillance with a colonoscopy, particularly in patients who have had a prior polypectomy, because of the higher risk.

Reasons patients may instead turn to FIT may include cost or other factors, she said.

To determine just how often that happens, how having a previous polypectomy affects FIT results, and how adherent patients are to follow up if a FIT result is positive, Wilson and her colleagues evaluated data from nearly 4.8 million individuals in the Veterans Health Administration Corporate Data Warehouse who underwent colonoscopy between 2000 and 2024.

Of the patients, 10.9% were found to have subsequently received interval FIT within 10 years of the index colonoscopy, and of those patients, nearly half (49.9%) had received a polypectomy at the index colonoscopy.

The average time from the colonoscopy/polypectomy to the interval FIT was 5.9 years (5.6 years in the polypectomy group vs 6.2 years in the non-polypectomy group).

Among the FIT screenings, results were positive in 17.2% of post-polypectomy patients and 14.1% of patients with no prior polypectomy, indicating a history of polypectomy to be predictive of a positive interval FIT (odds ratio [OR], 1.12; P < .0001).

Notably, while a follow-up colonoscopy is considered essential following a positive FIT result — and having a previous polypectomy should add further urgency to the matter — the study showed only 50.4% of those who had an earlier polypectomy went on to receive the recommended follow-up colonoscopy after a positive follow-up FIT, and the rate was 49.3% among those who had not received a polypectomy (P = .001).

For those who did receive a follow-up colonoscopy after a positive FIT, the duration of time to receiving the colonoscopy was longer among those who had a prior polypectomy, at 2.9 months compared with 2.5 months in the non-polypectomy group (P < .001).

Colonoscopy results following a positive FIT showed higher rates of detections among patients who had prior polypectomies than among those with no prior polypectomy, including tubular adenomas (54.7% vs 45.8%), tubulovillous adenomas (5.6% vs 4.7%), adenomas with high-grade dysplasia (0.8% vs 0.7%), sessile serrated lesions (3.52% vs 2.4%), advanced colorectal neoplasia (9.2% vs 7.9%), and colorectal cancer (3.3% vs 3.0%).

However, a prior polypectomy was not independently predictive of colorectal cancer (OR, 0.96; P = .65) or advanced colorectal neoplasia (OR, 0.97; P = .57) in the post-colonoscopy interval FIT.

The findings underscore that “positive results carried a high risk of advanced neoplasia or cancer, irrespective of prior polypectomy history,” Wilson said.

 

Clinicians Must ‘Do a Better Job’

Commenting on the study, William D. Chey, MD, AGAF, chief of the Division of Gastroenterology & Hepatology at the University of Michigan in Ann Arbor, noted that the study “addresses one of the biggest challenges we face as a profession, which is making sure that patients who have a positive stool test get a colonoscopy.”

He noted that the low rate of just 50% of recipients of positive FITs going on to receive a colonoscopy is consistent with what is observed in other trials.

“Other data suggests that the rate might even be significantly higher — at 70%-80%, depending upon the population and the test,” Chey told Medscape Medical News.

Reasons for the failure to receive the follow-up testing range from income restrictions (due to the high cost of a colonoscopy, especially if not covered by insurance), education, speaking a foreign language, and other factors, he said.

The relatively high rates of colon cancers detected by FIT in the study, in those with and without a prior polypectomy, along with findings from other studies “should raise questions about whether there might be a role for FIT testing in addition to colonoscopy.” However, much stronger evidence would be needed, Chey noted.

In the meantime, a key issue is “how do we do a better job of making sure that individuals who have a positive FIT test get a colonoscopy,” he said.

“I think a lot of this is going to come down to how it’s done at the primary care level.”

Chey added that in that, and any other setting, “the main message that needs to get out to people who are undergoing stool-based screening is that the stool test is only the first part of the screening process, and if it’s positive, a follow-up colonoscopy must be performed.”

“Otherwise, the stool-based test is of no value.”

Wilson had no disclosures to report. Chey’s disclosures included consulting and/or other relationships with Ardelyx, Atmo, Biomerica, Commonwealth Diagnostics International, Corprata, Dieta, Evinature, Food Marble, Gemelli, Kiwi BioScience, Modify Health, Nestlé, Phathom, Redhill, Salix/Valeant, Takeda, and Vibrant.

 

A version of this article appeared on Medscape.com . 

Due to the underlying mechanism of atrial fibrillation (Afib), clots can form within the left atrial appendage. Clots that become dislodged may lead to ischemic stroke and possibly death. The 2023 guidelines for atrial fibrillation from the American College of Cardiology and American Heart Association recommend anticoagulation therapy for patients with an Afib diagnosis and a CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke/vascular disease, age 65 to 74 years, and female sex) score pertinent for ≥ 1 non–sex-related factor (score ≥ 2 for women; ≥ 1 for men) to prevent stroke-related complications. The CHA₂DS₂-VASc score is a 9-point scoring tool based on comorbidities and conditions that increase risk of stroke in patients with Afib. Each value correlates to an annualized stroke risk percentage that increases as the score increases.

In clinical practice, patients meeting these thresholds are indicated for anticoagulation and are considered for indefinite use unless ≥ 1 of the following conditions are present: bleeding risk outweighs the stroke prevention benefit, Afib is episodic (< 48 hours) or a nonpharmacologic intervention, such as a left atrial appendage occlusion (LAAO) device is present.¹

In patients with a diagnosed venous thromboembolism (VTE), such as deep vein thrombosis or pulmonary embolism, anticoagulation is used to treat the current thrombosis and prevent embolization that can ultimately lead to death. The 2021 guideline for VTE from the American College of Chest Physicians identifies certain risk factors that increase risk for VTE and categorizes them as transient or persistent. Transient risk factors include hospitalization > 3 days, major trauma, surgery, cast immobilization, hormone therapy, pregnancy, or prolonged travel > 8 hours. Persistent risk factors include malignancy, thrombophilia, and certain medications.

The guideline recommends therapy durations based on event frequency, the presence and classification of provoking risk factors, and bleeding risk. As the risk of recurrent thrombosis and other potential complications is greatest in the first 3 to 6 months after a diagnosed event, at least 3 months anticoagulation therapy is recommended following VTE diagnosis. At the 3-month mark, all regimens are suggested to be re-evaluated and considered for extended treatment duration if the event was unprovoked, recurrent, secondary to a persistent risk factor, or low bleed risk.²Anticoagulation is an important guideline-recommended pharmacologic intervention for various disease states, although its use is not without risks. The Institute for Safe Medication Practices has classified oral anticoagulants as high-alert medications. This designation was made because anticoagulant medications have the potential to cause harm when used or omitted in error and lead to life-threatening bleed or thrombotic complications.³Anticoagulation stewardship ensures that anticoagulation therapy is appropriately initiated, maintained, and discontinued when indicated. Because of the potential for harm, anticoagulation stewardship is an important part of Afib and VTE management. Pharmacists can help verify and evaluate anticoagulation therapies. Research suggests that pharmacist-led anticoagulation stewardship efforts may play a role in ensuring safer patient outcomes.⁴The purpose of this quality improvement (QI) study was to implement pharmacist-led anticoagulation stewardship practices at Veterans Affairs Phoenix Health Care System (VAPHCS) to identify veterans with Afib not currently on anticoagulation, as well as to identify veterans with a history of VTE events who have completed a sufficient treatment duration.

Methods

Anticoagulation stewardship efforts were implemented in 2 cohorts of patients: those with Afib who may be indicated to initiate anticoagulation, and those with a history of VTE events who may be indicated to consider anticoagulation discontinuation. Patient records were reviewed using a standardized note template, and recommendations to either initiate or discontinue anticoagulation therapy were documented. The VAPHCS Research Service reviewed this study and determined that it was not research and was exempt from institutional review board review.

Atrial Fibrillation Cohort

A population health dashboard created by the Stroke Prevention in Atrial Fibrillation/Flutter Targeting the uNTreated: a focus on health care disparities (SPAFF-TNT-D) national VA study team was used to identify veterans at VAPHCS with a diagnosis of Afib without an active VA prescription for an anticoagulant. The dashboard filtered and produced data points from the medical record that correlated to the components of the CHA₂DS₂-VASc score. All veterans identified by the dashboard with scores of 7 or 8 were included. No patients had a score of 9. Comprehensive chart reviews of available VA and non–VA-provided care records were conducted by the investigators, and a standardized note template designed by the SPAFF-TNT-D team (eAppendix 1) was used to document findings within the electronic health record (EHR). If anticoagulation was deemed to be indicated, the assigned primary care practitioner (PCP) as listed in the EHR was alerted to the note by the investigators for further evaluation and consideration of prescribing anticoagulation.

Venous Thromboembolism Cohort

VAPHCS pharmacy informatics pulled data that included veterans with documented VTE and an active VA anticoagulant prescription between November 2022 and November 2023. Veterans were reviewed in chronological order based on when the anticoagulant prescription was written. All veterans were included until an equal number of charts were reviewed in both the Afib and VTE cohorts. Comprehensive chart review of available VA- and non–VA-provided care records was conducted by the investigators, and a standardized note template as designed by the investigators (eAppendix 2) was used to document findings within the EHR. If the duration of anticoagulation therapy was deemed sufficient, the assigned anticoagulation clinical pharmacist practitioner (CPP) was alerted to the note by the investigators for further evaluation and consideration of discontinuing anticoagulation.

EHR reviews were conducted in October and November 2023 and lasted about 10 to 20 minutes per patient. To evaluate completeness and accuracy of the documented findings within the EHR, both investigators reviewed and cosigned the completed note template and verified the correct PCP was alerted to the recommendation for appropriate continuity of care. Results were reviewed in March 2024.

Outcomes

Atrial fibrillation cohort. The primary outcome was the number of veterans with Afib who were recommended to start anticoagulation therapy. Additional outcomes evaluated included the number of interventions completed, action taken by PCPs in response to the provided recommendation, and reasons provided by the investigators for not recommending initiation of anticoagulation therapy in specific veteran cases.

Venous thromboembolism cohort. The primary outcome was the number of veterans with a history of VTE events recommended to discontinue anticoagulation therapy. Additional outcomes included number of interventions completed, action taken by the anticoagulation CPP in response to the provided recommendation, and reasons provided by the investigators for not recommending discontinuation of anticoagulation therapy in specific veteran cases.

Analysis

Sample size was determined by the inclusion criteria and was not designed to attain statistical power. Data embedded in the Afib cohort standardized note template, also known as health factors, were later used for data analysis. Recommendations in the VTE cohort were manually tracked and recorded by the investigators. Results for this study were analyzed using descriptive statistics.

Results

A total of 114 veterans were reviewed and included in this study: 57 in each cohort. Seven recommendations were made regarding anticoagulation initiation for patients with Afib and 7 were made for anticoagulation discontinuation for patients with VTE (Table 1).

In the Afib cohort, 1 veteran was successfully initiated on anticoagulation therapy and 1 veteran was deemed appropriate for initiation of anticoagulation but was not reachable. Of the 5 recommendations with no action taken, 4 PCPs acknowledged the alert with no further documentation, and 1 PCP deferred the decision to cardiology with no further documentation. In the VTE cohort, 3 veterans successfully discontinued anticoagulation therapy and 2 veterans were further evaluated by the anticoagulation CPP and deemed appropriate to continue therapy based on potential for malignancy. Of the 2 recommendations with no action taken, 1 anticoagulation CPP acknowledged the alert with no further documentation and 1 anticoagulation CPP suggested further evaluation by PCP with no further documentation.

In the Afib cohort, a nonpharmacologic approach was defined as documentation of a LAAO device. An inaccurate diagnosis was defined as an Afib diagnosis being used in a previous visit, although there was no further confirmation of diagnosis via chart review. Veterans classified as already being on anticoagulation had documentation of non–VA-written anticoagulant prescriptions or receiving a supply of anticoagulants from a facility such as a nursing home. Anticoagulation was defined as unfavorable if a documented risk/benefit conversation was found via EHR review. Anticoagulation was defined as not indicated if the Afib was documented as transient, episodic, or historical (Table 2).

In the VTE cohort, no recommendations for discontinuation were made for veterans indicated to continue anticoagulation due to a concurrent Afib diagnosis. Chronic or recurrent events were defined as documentation of multiple VTE events and associated dates in the EHR. Persistent risk factors included malignancy or medications contributing to hypercoagulable states. Thrombophilia was defined as having documentation of a diagnosis in the EHR. An unprovoked event was defined as VTE without any documented transient risk factors (eg, hospitalization, trauma, surgery, cast immobilization, hormone therapy, pregnancy, or prolonged travel). Anticoagulation had already been discontinued in 1 veteran after the data were collected but before chart review occurred (Table 3).

Discussion

Pharmacy-led indication reviews resulted in appropriate recommendations for anticoagulation use in veterans with Afib and a history of VTE events. Overall, 12.3% of chart reviews in each cohort resulted in a recommendation being made, which was similar to the rate found by Koolian et al.⁵ In that study, 10% of recommendations were related to initiation or interruption of anticoagulation. This recommendation category consisted of several subcategories, including “suggesting therapeutic anticoagulation when none is currently ordered” and “suggesting anticoagulation cessation if no longer indicated,” but specific numerical prevalence was not provided.⁵

Online dashboard use allowed for greater population health management and identification of veterans with Afib who were not on active anticoagulation, providing opportunities to prevent stroke-related complications. Wang et al completed a similarly designed study that included a population health tool to identify patients with Afib who were not on anticoagulation and implemented pharmacist-led chart review and facilitation of recommendations to the responsible clinician. This study reviewed 1727 patients and recommended initiation of anticoagulation therapy for 75 (4.3%).⁶ The current study had a higher percentage of patients with recommendations for changes despite its smaller size.

Evaluating the duration of therapy for anticoagulation in veterans with a history of VTE events provided an opportunity to reduce unnecessary exposure to anticoagulation and minimize bleeding risks. Using a chart review process and standardized note template enabled the documentation of pertinent information that could be readily reviewed by the PCP. This process is a step toward ensuring VAPHCS PCPs provide guideline-recommended care and actively prevent stroke and bleeding complications. Adoption of this process into the current VAPHCS Anticoagulation Clinic workflow for review of veterans with either Afib or VTE could lead to more EHRs being reviewed and recommendations made, ultimately improving patient outcomes. 

Therapeutic interventions based on the recommendations were completed for 1 of 7 veterans (14%) and 3 of 7 veterans (43%) in the Afib and VTE cohorts, respectively. The prevalence of completed interventions in this anticoagulation stewardship study was higher than those in Wang et al, who found only 9% of their recommendations resulted in PCPs considering action related to anticoagulation, and only 4% were successfully initiated.⁶

In the Afib cohort, veterans identified by the dashboard with a CHA₂DS₂-VASc of 7 or 8 were prioritized for review. Reviewing these veterans ensured that patients with the highest stroke risk were sufficiently evaluated and started on anticoagulation as needed to reduce stroke-related complications. In contrast, because these veterans had higher CHA₂DS₂-VASc scores, they may have already been evaluated for anticoagulation in the past and had a documented rationale for not being placed on anticoagulation (LAAO device placement was the most common rationale). Focusing on veterans with a lower CHA₂DS₂-VASc score such as 1 for men or 2 for women could potentially include more opportunities for recommendations. Although stroke risk may be lower in this population compared with those with higher CHA₂DS₂-VASc scores, guideline-recommended anticoagulation use may be missed for these patients. 

In the VTE cohort, veterans with an anticoagulant prescription written 12 months before data collection were prioritized for review. Reviewing these veterans ensured that anticoagulation therapy met guideline recommendations of at least 3 months, with potential for extended duration upon further evaluation by a provider at that time. Based on collected results, most veterans were already reevaluated and had documented reasons why anticoagulation was still indicated; concurrent Afib was most common followed by chronic or recurrent VTE. Reviewing veterans with more recent prescriptions just over the recommended 3-month duration could potentially include more opportunities for recommendations to be made. It is more likely that by 3 months another PCP had not already weighed in on the duration of therapy, and the anticoagulation CPP could ensure a thorough review is conducted with guideline-based recommendations.

Most published literature on anticoagulation stewardship efforts is focused on inpatient management and policy changes, or concentrate on attributes of therapy such as appropriate dosing and drug interactions. This study highlighted that gaps in care related to anticoagulation use and discontinuation are present in the VAPHCS population and can be appropriately addressed via pharmacist-led indication reviews. Future studies designed to focus on initiating anticoagulation where appropriate, and discontinuing where a sufficient treatment period has been completed, are warranted to minimize this gap in care and allow health systems to work toward process changes to ensure safe and optimized care is provided for the patients they serve.

Limitations

In the Afib cohort, 5 of 7 recommendations (71%) had no further action taken by the PCP, which may represent a barrier to care. In contrast, 2 of 7 recommendations (29%) had no further action in the VTE cohort. It is possible that the difference can be attributed to the anticoagulation CPP receiving VTE alerts and PCPs receiving Afib alerts. The anticoagulation CPP was familiar with this QI study and may have better understood the purpose of the chart review and the need to provide a timely response. PCPs may have been less likely to take action because they were unfamiliar with the anticoagulation stewardship initiative and standardized note template or overwhelmed by too many EHR alerts.

The lack of PCP response to a virtual alert or message also was observed by Wang et al, whereas Koolian et al reported higher intervention completion rates, with verbal recommendations being made to the responsible clinicians. To further ensure these pertinent recommendations for anticoagulation initiation in veterans with Afib are properly reviewed and evaluated, future research could include intentional follow-up with the PCP regarding the alert, PCP-specific education about the anticoagulation stewardship initiative and the role of the standardized note template, and collaboration with PCPs to identify alternative ways to relay recommendations in a way that would ensure the completion of appropriate and timely review.

Conclusions

This study identified gaps in care related to anticoagulation needs in the VAPHCS veteran population. Utilizing a standardized indication review process allows pharmacists to evaluate anticoagulant use for both appropriate indication and duration of therapy. Providing recommendations via chart review notes and alerting respective PCPs and CPPs results in veterans receiving safe and optimized care regarding their anticoagulation needs.

Due to the underlying mechanism of atrial fibrillation (Afib), clots can form within the left atrial appendage. Clots that become dislodged may lead to ischemic stroke and possibly death. The 2023 guidelines for atrial fibrillation from the American College of Cardiology and American Heart Association recommend anticoagulation therapy for patients with an Afib diagnosis and a CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke/vascular disease, age 65 to 74 years, and female sex) score pertinent for ≥ 1 non–sex-related factor (score ≥ 2 for women; ≥ 1 for men) to prevent stroke-related complications. The CHA₂DS₂-VASc score is a 9-point scoring tool based on comorbidities and conditions that increase risk of stroke in patients with Afib. Each value correlates to an annualized stroke risk percentage that increases as the score increases.

In clinical practice, patients meeting these thresholds are indicated for anticoagulation and are considered for indefinite use unless ≥ 1 of the following conditions are present: bleeding risk outweighs the stroke prevention benefit, Afib is episodic (< 48 hours) or a nonpharmacologic intervention, such as a left atrial appendage occlusion (LAAO) device is present.¹

In patients with a diagnosed venous thromboembolism (VTE), such as deep vein thrombosis or pulmonary embolism, anticoagulation is used to treat the current thrombosis and prevent embolization that can ultimately lead to death. The 2021 guideline for VTE from the American College of Chest Physicians identifies certain risk factors that increase risk for VTE and categorizes them as transient or persistent. Transient risk factors include hospitalization > 3 days, major trauma, surgery, cast immobilization, hormone therapy, pregnancy, or prolonged travel > 8 hours. Persistent risk factors include malignancy, thrombophilia, and certain medications.

The guideline recommends therapy durations based on event frequency, the presence and classification of provoking risk factors, and bleeding risk. As the risk of recurrent thrombosis and other potential complications is greatest in the first 3 to 6 months after a diagnosed event, at least 3 months anticoagulation therapy is recommended following VTE diagnosis. At the 3-month mark, all regimens are suggested to be re-evaluated and considered for extended treatment duration if the event was unprovoked, recurrent, secondary to a persistent risk factor, or low bleed risk.²Anticoagulation is an important guideline-recommended pharmacologic intervention for various disease states, although its use is not without risks. The Institute for Safe Medication Practices has classified oral anticoagulants as high-alert medications. This designation was made because anticoagulant medications have the potential to cause harm when used or omitted in error and lead to life-threatening bleed or thrombotic complications.³Anticoagulation stewardship ensures that anticoagulation therapy is appropriately initiated, maintained, and discontinued when indicated. Because of the potential for harm, anticoagulation stewardship is an important part of Afib and VTE management. Pharmacists can help verify and evaluate anticoagulation therapies. Research suggests that pharmacist-led anticoagulation stewardship efforts may play a role in ensuring safer patient outcomes.⁴The purpose of this quality improvement (QI) study was to implement pharmacist-led anticoagulation stewardship practices at Veterans Affairs Phoenix Health Care System (VAPHCS) to identify veterans with Afib not currently on anticoagulation, as well as to identify veterans with a history of VTE events who have completed a sufficient treatment duration.

Methods

Anticoagulation stewardship efforts were implemented in 2 cohorts of patients: those with Afib who may be indicated to initiate anticoagulation, and those with a history of VTE events who may be indicated to consider anticoagulation discontinuation. Patient records were reviewed using a standardized note template, and recommendations to either initiate or discontinue anticoagulation therapy were documented. The VAPHCS Research Service reviewed this study and determined that it was not research and was exempt from institutional review board review.

Atrial Fibrillation Cohort

A population health dashboard created by the Stroke Prevention in Atrial Fibrillation/Flutter Targeting the uNTreated: a focus on health care disparities (SPAFF-TNT-D) national VA study team was used to identify veterans at VAPHCS with a diagnosis of Afib without an active VA prescription for an anticoagulant. The dashboard filtered and produced data points from the medical record that correlated to the components of the CHA₂DS₂-VASc score. All veterans identified by the dashboard with scores of 7 or 8 were included. No patients had a score of 9. Comprehensive chart reviews of available VA and non–VA-provided care records were conducted by the investigators, and a standardized note template designed by the SPAFF-TNT-D team (eAppendix 1) was used to document findings within the electronic health record (EHR). If anticoagulation was deemed to be indicated, the assigned primary care practitioner (PCP) as listed in the EHR was alerted to the note by the investigators for further evaluation and consideration of prescribing anticoagulation.

Venous Thromboembolism Cohort

VAPHCS pharmacy informatics pulled data that included veterans with documented VTE and an active VA anticoagulant prescription between November 2022 and November 2023. Veterans were reviewed in chronological order based on when the anticoagulant prescription was written. All veterans were included until an equal number of charts were reviewed in both the Afib and VTE cohorts. Comprehensive chart review of available VA- and non–VA-provided care records was conducted by the investigators, and a standardized note template as designed by the investigators (eAppendix 2) was used to document findings within the EHR. If the duration of anticoagulation therapy was deemed sufficient, the assigned anticoagulation clinical pharmacist practitioner (CPP) was alerted to the note by the investigators for further evaluation and consideration of discontinuing anticoagulation.

EHR reviews were conducted in October and November 2023 and lasted about 10 to 20 minutes per patient. To evaluate completeness and accuracy of the documented findings within the EHR, both investigators reviewed and cosigned the completed note template and verified the correct PCP was alerted to the recommendation for appropriate continuity of care. Results were reviewed in March 2024.

Outcomes

Atrial fibrillation cohort. The primary outcome was the number of veterans with Afib who were recommended to start anticoagulation therapy. Additional outcomes evaluated included the number of interventions completed, action taken by PCPs in response to the provided recommendation, and reasons provided by the investigators for not recommending initiation of anticoagulation therapy in specific veteran cases.

Venous thromboembolism cohort. The primary outcome was the number of veterans with a history of VTE events recommended to discontinue anticoagulation therapy. Additional outcomes included number of interventions completed, action taken by the anticoagulation CPP in response to the provided recommendation, and reasons provided by the investigators for not recommending discontinuation of anticoagulation therapy in specific veteran cases.

Analysis

Sample size was determined by the inclusion criteria and was not designed to attain statistical power. Data embedded in the Afib cohort standardized note template, also known as health factors, were later used for data analysis. Recommendations in the VTE cohort were manually tracked and recorded by the investigators. Results for this study were analyzed using descriptive statistics.

Results

A total of 114 veterans were reviewed and included in this study: 57 in each cohort. Seven recommendations were made regarding anticoagulation initiation for patients with Afib and 7 were made for anticoagulation discontinuation for patients with VTE (Table 1).

In the Afib cohort, 1 veteran was successfully initiated on anticoagulation therapy and 1 veteran was deemed appropriate for initiation of anticoagulation but was not reachable. Of the 5 recommendations with no action taken, 4 PCPs acknowledged the alert with no further documentation, and 1 PCP deferred the decision to cardiology with no further documentation. In the VTE cohort, 3 veterans successfully discontinued anticoagulation therapy and 2 veterans were further evaluated by the anticoagulation CPP and deemed appropriate to continue therapy based on potential for malignancy. Of the 2 recommendations with no action taken, 1 anticoagulation CPP acknowledged the alert with no further documentation and 1 anticoagulation CPP suggested further evaluation by PCP with no further documentation.

In the Afib cohort, a nonpharmacologic approach was defined as documentation of a LAAO device. An inaccurate diagnosis was defined as an Afib diagnosis being used in a previous visit, although there was no further confirmation of diagnosis via chart review. Veterans classified as already being on anticoagulation had documentation of non–VA-written anticoagulant prescriptions or receiving a supply of anticoagulants from a facility such as a nursing home. Anticoagulation was defined as unfavorable if a documented risk/benefit conversation was found via EHR review. Anticoagulation was defined as not indicated if the Afib was documented as transient, episodic, or historical (Table 2).

In the VTE cohort, no recommendations for discontinuation were made for veterans indicated to continue anticoagulation due to a concurrent Afib diagnosis. Chronic or recurrent events were defined as documentation of multiple VTE events and associated dates in the EHR. Persistent risk factors included malignancy or medications contributing to hypercoagulable states. Thrombophilia was defined as having documentation of a diagnosis in the EHR. An unprovoked event was defined as VTE without any documented transient risk factors (eg, hospitalization, trauma, surgery, cast immobilization, hormone therapy, pregnancy, or prolonged travel). Anticoagulation had already been discontinued in 1 veteran after the data were collected but before chart review occurred (Table 3).

Discussion

Pharmacy-led indication reviews resulted in appropriate recommendations for anticoagulation use in veterans with Afib and a history of VTE events. Overall, 12.3% of chart reviews in each cohort resulted in a recommendation being made, which was similar to the rate found by Koolian et al.⁵ In that study, 10% of recommendations were related to initiation or interruption of anticoagulation. This recommendation category consisted of several subcategories, including “suggesting therapeutic anticoagulation when none is currently ordered” and “suggesting anticoagulation cessation if no longer indicated,” but specific numerical prevalence was not provided.⁵

Online dashboard use allowed for greater population health management and identification of veterans with Afib who were not on active anticoagulation, providing opportunities to prevent stroke-related complications. Wang et al completed a similarly designed study that included a population health tool to identify patients with Afib who were not on anticoagulation and implemented pharmacist-led chart review and facilitation of recommendations to the responsible clinician. This study reviewed 1727 patients and recommended initiation of anticoagulation therapy for 75 (4.3%).⁶ The current study had a higher percentage of patients with recommendations for changes despite its smaller size.

Evaluating the duration of therapy for anticoagulation in veterans with a history of VTE events provided an opportunity to reduce unnecessary exposure to anticoagulation and minimize bleeding risks. Using a chart review process and standardized note template enabled the documentation of pertinent information that could be readily reviewed by the PCP. This process is a step toward ensuring VAPHCS PCPs provide guideline-recommended care and actively prevent stroke and bleeding complications. Adoption of this process into the current VAPHCS Anticoagulation Clinic workflow for review of veterans with either Afib or VTE could lead to more EHRs being reviewed and recommendations made, ultimately improving patient outcomes. 

Therapeutic interventions based on the recommendations were completed for 1 of 7 veterans (14%) and 3 of 7 veterans (43%) in the Afib and VTE cohorts, respectively. The prevalence of completed interventions in this anticoagulation stewardship study was higher than those in Wang et al, who found only 9% of their recommendations resulted in PCPs considering action related to anticoagulation, and only 4% were successfully initiated.⁶

In the Afib cohort, veterans identified by the dashboard with a CHA₂DS₂-VASc of 7 or 8 were prioritized for review. Reviewing these veterans ensured that patients with the highest stroke risk were sufficiently evaluated and started on anticoagulation as needed to reduce stroke-related complications. In contrast, because these veterans had higher CHA₂DS₂-VASc scores, they may have already been evaluated for anticoagulation in the past and had a documented rationale for not being placed on anticoagulation (LAAO device placement was the most common rationale). Focusing on veterans with a lower CHA₂DS₂-VASc score such as 1 for men or 2 for women could potentially include more opportunities for recommendations. Although stroke risk may be lower in this population compared with those with higher CHA₂DS₂-VASc scores, guideline-recommended anticoagulation use may be missed for these patients. 

In the VTE cohort, veterans with an anticoagulant prescription written 12 months before data collection were prioritized for review. Reviewing these veterans ensured that anticoagulation therapy met guideline recommendations of at least 3 months, with potential for extended duration upon further evaluation by a provider at that time. Based on collected results, most veterans were already reevaluated and had documented reasons why anticoagulation was still indicated; concurrent Afib was most common followed by chronic or recurrent VTE. Reviewing veterans with more recent prescriptions just over the recommended 3-month duration could potentially include more opportunities for recommendations to be made. It is more likely that by 3 months another PCP had not already weighed in on the duration of therapy, and the anticoagulation CPP could ensure a thorough review is conducted with guideline-based recommendations.

Most published literature on anticoagulation stewardship efforts is focused on inpatient management and policy changes, or concentrate on attributes of therapy such as appropriate dosing and drug interactions. This study highlighted that gaps in care related to anticoagulation use and discontinuation are present in the VAPHCS population and can be appropriately addressed via pharmacist-led indication reviews. Future studies designed to focus on initiating anticoagulation where appropriate, and discontinuing where a sufficient treatment period has been completed, are warranted to minimize this gap in care and allow health systems to work toward process changes to ensure safe and optimized care is provided for the patients they serve.

Limitations

In the Afib cohort, 5 of 7 recommendations (71%) had no further action taken by the PCP, which may represent a barrier to care. In contrast, 2 of 7 recommendations (29%) had no further action in the VTE cohort. It is possible that the difference can be attributed to the anticoagulation CPP receiving VTE alerts and PCPs receiving Afib alerts. The anticoagulation CPP was familiar with this QI study and may have better understood the purpose of the chart review and the need to provide a timely response. PCPs may have been less likely to take action because they were unfamiliar with the anticoagulation stewardship initiative and standardized note template or overwhelmed by too many EHR alerts.

The lack of PCP response to a virtual alert or message also was observed by Wang et al, whereas Koolian et al reported higher intervention completion rates, with verbal recommendations being made to the responsible clinicians. To further ensure these pertinent recommendations for anticoagulation initiation in veterans with Afib are properly reviewed and evaluated, future research could include intentional follow-up with the PCP regarding the alert, PCP-specific education about the anticoagulation stewardship initiative and the role of the standardized note template, and collaboration with PCPs to identify alternative ways to relay recommendations in a way that would ensure the completion of appropriate and timely review.

Conclusions

This study identified gaps in care related to anticoagulation needs in the VAPHCS veteran population. Utilizing a standardized indication review process allows pharmacists to evaluate anticoagulant use for both appropriate indication and duration of therapy. Providing recommendations via chart review notes and alerting respective PCPs and CPPs results in veterans receiving safe and optimized care regarding their anticoagulation needs.

Due to the underlying mechanism of atrial fibrillation (Afib), clots can form within the left atrial appendage. Clots that become dislodged may lead to ischemic stroke and possibly death. The 2023 guidelines for atrial fibrillation from the American College of Cardiology and American Heart Association recommend anticoagulation therapy for patients with an Afib diagnosis and a CHA₂DS₂-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke/vascular disease, age 65 to 74 years, and female sex) score pertinent for ≥ 1 non–sex-related factor (score ≥ 2 for women; ≥ 1 for men) to prevent stroke-related complications. The CHA₂DS₂-VASc score is a 9-point scoring tool based on comorbidities and conditions that increase risk of stroke in patients with Afib. Each value correlates to an annualized stroke risk percentage that increases as the score increases.

In clinical practice, patients meeting these thresholds are indicated for anticoagulation and are considered for indefinite use unless ≥ 1 of the following conditions are present: bleeding risk outweighs the stroke prevention benefit, Afib is episodic (< 48 hours) or a nonpharmacologic intervention, such as a left atrial appendage occlusion (LAAO) device is present.¹

In patients with a diagnosed venous thromboembolism (VTE), such as deep vein thrombosis or pulmonary embolism, anticoagulation is used to treat the current thrombosis and prevent embolization that can ultimately lead to death. The 2021 guideline for VTE from the American College of Chest Physicians identifies certain risk factors that increase risk for VTE and categorizes them as transient or persistent. Transient risk factors include hospitalization > 3 days, major trauma, surgery, cast immobilization, hormone therapy, pregnancy, or prolonged travel > 8 hours. Persistent risk factors include malignancy, thrombophilia, and certain medications.

The guideline recommends therapy durations based on event frequency, the presence and classification of provoking risk factors, and bleeding risk. As the risk of recurrent thrombosis and other potential complications is greatest in the first 3 to 6 months after a diagnosed event, at least 3 months anticoagulation therapy is recommended following VTE diagnosis. At the 3-month mark, all regimens are suggested to be re-evaluated and considered for extended treatment duration if the event was unprovoked, recurrent, secondary to a persistent risk factor, or low bleed risk.²Anticoagulation is an important guideline-recommended pharmacologic intervention for various disease states, although its use is not without risks. The Institute for Safe Medication Practices has classified oral anticoagulants as high-alert medications. This designation was made because anticoagulant medications have the potential to cause harm when used or omitted in error and lead to life-threatening bleed or thrombotic complications.³Anticoagulation stewardship ensures that anticoagulation therapy is appropriately initiated, maintained, and discontinued when indicated. Because of the potential for harm, anticoagulation stewardship is an important part of Afib and VTE management. Pharmacists can help verify and evaluate anticoagulation therapies. Research suggests that pharmacist-led anticoagulation stewardship efforts may play a role in ensuring safer patient outcomes.⁴The purpose of this quality improvement (QI) study was to implement pharmacist-led anticoagulation stewardship practices at Veterans Affairs Phoenix Health Care System (VAPHCS) to identify veterans with Afib not currently on anticoagulation, as well as to identify veterans with a history of VTE events who have completed a sufficient treatment duration.

Methods

Anticoagulation stewardship efforts were implemented in 2 cohorts of patients: those with Afib who may be indicated to initiate anticoagulation, and those with a history of VTE events who may be indicated to consider anticoagulation discontinuation. Patient records were reviewed using a standardized note template, and recommendations to either initiate or discontinue anticoagulation therapy were documented. The VAPHCS Research Service reviewed this study and determined that it was not research and was exempt from institutional review board review.

Atrial Fibrillation Cohort

A population health dashboard created by the Stroke Prevention in Atrial Fibrillation/Flutter Targeting the uNTreated: a focus on health care disparities (SPAFF-TNT-D) national VA study team was used to identify veterans at VAPHCS with a diagnosis of Afib without an active VA prescription for an anticoagulant. The dashboard filtered and produced data points from the medical record that correlated to the components of the CHA₂DS₂-VASc score. All veterans identified by the dashboard with scores of 7 or 8 were included. No patients had a score of 9. Comprehensive chart reviews of available VA and non–VA-provided care records were conducted by the investigators, and a standardized note template designed by the SPAFF-TNT-D team (eAppendix 1) was used to document findings within the electronic health record (EHR). If anticoagulation was deemed to be indicated, the assigned primary care practitioner (PCP) as listed in the EHR was alerted to the note by the investigators for further evaluation and consideration of prescribing anticoagulation.

Venous Thromboembolism Cohort

VAPHCS pharmacy informatics pulled data that included veterans with documented VTE and an active VA anticoagulant prescription between November 2022 and November 2023. Veterans were reviewed in chronological order based on when the anticoagulant prescription was written. All veterans were included until an equal number of charts were reviewed in both the Afib and VTE cohorts. Comprehensive chart review of available VA- and non–VA-provided care records was conducted by the investigators, and a standardized note template as designed by the investigators (eAppendix 2) was used to document findings within the EHR. If the duration of anticoagulation therapy was deemed sufficient, the assigned anticoagulation clinical pharmacist practitioner (CPP) was alerted to the note by the investigators for further evaluation and consideration of discontinuing anticoagulation.

EHR reviews were conducted in October and November 2023 and lasted about 10 to 20 minutes per patient. To evaluate completeness and accuracy of the documented findings within the EHR, both investigators reviewed and cosigned the completed note template and verified the correct PCP was alerted to the recommendation for appropriate continuity of care. Results were reviewed in March 2024.

Outcomes

Atrial fibrillation cohort. The primary outcome was the number of veterans with Afib who were recommended to start anticoagulation therapy. Additional outcomes evaluated included the number of interventions completed, action taken by PCPs in response to the provided recommendation, and reasons provided by the investigators for not recommending initiation of anticoagulation therapy in specific veteran cases.

Venous thromboembolism cohort. The primary outcome was the number of veterans with a history of VTE events recommended to discontinue anticoagulation therapy. Additional outcomes included number of interventions completed, action taken by the anticoagulation CPP in response to the provided recommendation, and reasons provided by the investigators for not recommending discontinuation of anticoagulation therapy in specific veteran cases.

Analysis

Sample size was determined by the inclusion criteria and was not designed to attain statistical power. Data embedded in the Afib cohort standardized note template, also known as health factors, were later used for data analysis. Recommendations in the VTE cohort were manually tracked and recorded by the investigators. Results for this study were analyzed using descriptive statistics.

Results

A total of 114 veterans were reviewed and included in this study: 57 in each cohort. Seven recommendations were made regarding anticoagulation initiation for patients with Afib and 7 were made for anticoagulation discontinuation for patients with VTE (Table 1).

In the Afib cohort, 1 veteran was successfully initiated on anticoagulation therapy and 1 veteran was deemed appropriate for initiation of anticoagulation but was not reachable. Of the 5 recommendations with no action taken, 4 PCPs acknowledged the alert with no further documentation, and 1 PCP deferred the decision to cardiology with no further documentation. In the VTE cohort, 3 veterans successfully discontinued anticoagulation therapy and 2 veterans were further evaluated by the anticoagulation CPP and deemed appropriate to continue therapy based on potential for malignancy. Of the 2 recommendations with no action taken, 1 anticoagulation CPP acknowledged the alert with no further documentation and 1 anticoagulation CPP suggested further evaluation by PCP with no further documentation.

In the Afib cohort, a nonpharmacologic approach was defined as documentation of a LAAO device. An inaccurate diagnosis was defined as an Afib diagnosis being used in a previous visit, although there was no further confirmation of diagnosis via chart review. Veterans classified as already being on anticoagulation had documentation of non–VA-written anticoagulant prescriptions or receiving a supply of anticoagulants from a facility such as a nursing home. Anticoagulation was defined as unfavorable if a documented risk/benefit conversation was found via EHR review. Anticoagulation was defined as not indicated if the Afib was documented as transient, episodic, or historical (Table 2).

In the VTE cohort, no recommendations for discontinuation were made for veterans indicated to continue anticoagulation due to a concurrent Afib diagnosis. Chronic or recurrent events were defined as documentation of multiple VTE events and associated dates in the EHR. Persistent risk factors included malignancy or medications contributing to hypercoagulable states. Thrombophilia was defined as having documentation of a diagnosis in the EHR. An unprovoked event was defined as VTE without any documented transient risk factors (eg, hospitalization, trauma, surgery, cast immobilization, hormone therapy, pregnancy, or prolonged travel). Anticoagulation had already been discontinued in 1 veteran after the data were collected but before chart review occurred (Table 3).

Discussion

Pharmacy-led indication reviews resulted in appropriate recommendations for anticoagulation use in veterans with Afib and a history of VTE events. Overall, 12.3% of chart reviews in each cohort resulted in a recommendation being made, which was similar to the rate found by Koolian et al.⁵ In that study, 10% of recommendations were related to initiation or interruption of anticoagulation. This recommendation category consisted of several subcategories, including “suggesting therapeutic anticoagulation when none is currently ordered” and “suggesting anticoagulation cessation if no longer indicated,” but specific numerical prevalence was not provided.⁵

Online dashboard use allowed for greater population health management and identification of veterans with Afib who were not on active anticoagulation, providing opportunities to prevent stroke-related complications. Wang et al completed a similarly designed study that included a population health tool to identify patients with Afib who were not on anticoagulation and implemented pharmacist-led chart review and facilitation of recommendations to the responsible clinician. This study reviewed 1727 patients and recommended initiation of anticoagulation therapy for 75 (4.3%).⁶ The current study had a higher percentage of patients with recommendations for changes despite its smaller size.

Evaluating the duration of therapy for anticoagulation in veterans with a history of VTE events provided an opportunity to reduce unnecessary exposure to anticoagulation and minimize bleeding risks. Using a chart review process and standardized note template enabled the documentation of pertinent information that could be readily reviewed by the PCP. This process is a step toward ensuring VAPHCS PCPs provide guideline-recommended care and actively prevent stroke and bleeding complications. Adoption of this process into the current VAPHCS Anticoagulation Clinic workflow for review of veterans with either Afib or VTE could lead to more EHRs being reviewed and recommendations made, ultimately improving patient outcomes. 

Therapeutic interventions based on the recommendations were completed for 1 of 7 veterans (14%) and 3 of 7 veterans (43%) in the Afib and VTE cohorts, respectively. The prevalence of completed interventions in this anticoagulation stewardship study was higher than those in Wang et al, who found only 9% of their recommendations resulted in PCPs considering action related to anticoagulation, and only 4% were successfully initiated.⁶

In the Afib cohort, veterans identified by the dashboard with a CHA₂DS₂-VASc of 7 or 8 were prioritized for review. Reviewing these veterans ensured that patients with the highest stroke risk were sufficiently evaluated and started on anticoagulation as needed to reduce stroke-related complications. In contrast, because these veterans had higher CHA₂DS₂-VASc scores, they may have already been evaluated for anticoagulation in the past and had a documented rationale for not being placed on anticoagulation (LAAO device placement was the most common rationale). Focusing on veterans with a lower CHA₂DS₂-VASc score such as 1 for men or 2 for women could potentially include more opportunities for recommendations. Although stroke risk may be lower in this population compared with those with higher CHA₂DS₂-VASc scores, guideline-recommended anticoagulation use may be missed for these patients. 

In the VTE cohort, veterans with an anticoagulant prescription written 12 months before data collection were prioritized for review. Reviewing these veterans ensured that anticoagulation therapy met guideline recommendations of at least 3 months, with potential for extended duration upon further evaluation by a provider at that time. Based on collected results, most veterans were already reevaluated and had documented reasons why anticoagulation was still indicated; concurrent Afib was most common followed by chronic or recurrent VTE. Reviewing veterans with more recent prescriptions just over the recommended 3-month duration could potentially include more opportunities for recommendations to be made. It is more likely that by 3 months another PCP had not already weighed in on the duration of therapy, and the anticoagulation CPP could ensure a thorough review is conducted with guideline-based recommendations.

Most published literature on anticoagulation stewardship efforts is focused on inpatient management and policy changes, or concentrate on attributes of therapy such as appropriate dosing and drug interactions. This study highlighted that gaps in care related to anticoagulation use and discontinuation are present in the VAPHCS population and can be appropriately addressed via pharmacist-led indication reviews. Future studies designed to focus on initiating anticoagulation where appropriate, and discontinuing where a sufficient treatment period has been completed, are warranted to minimize this gap in care and allow health systems to work toward process changes to ensure safe and optimized care is provided for the patients they serve.

Limitations

In the Afib cohort, 5 of 7 recommendations (71%) had no further action taken by the PCP, which may represent a barrier to care. In contrast, 2 of 7 recommendations (29%) had no further action in the VTE cohort. It is possible that the difference can be attributed to the anticoagulation CPP receiving VTE alerts and PCPs receiving Afib alerts. The anticoagulation CPP was familiar with this QI study and may have better understood the purpose of the chart review and the need to provide a timely response. PCPs may have been less likely to take action because they were unfamiliar with the anticoagulation stewardship initiative and standardized note template or overwhelmed by too many EHR alerts.

The lack of PCP response to a virtual alert or message also was observed by Wang et al, whereas Koolian et al reported higher intervention completion rates, with verbal recommendations being made to the responsible clinicians. To further ensure these pertinent recommendations for anticoagulation initiation in veterans with Afib are properly reviewed and evaluated, future research could include intentional follow-up with the PCP regarding the alert, PCP-specific education about the anticoagulation stewardship initiative and the role of the standardized note template, and collaboration with PCPs to identify alternative ways to relay recommendations in a way that would ensure the completion of appropriate and timely review.

Conclusions

This study identified gaps in care related to anticoagulation needs in the VAPHCS veteran population. Utilizing a standardized indication review process allows pharmacists to evaluate anticoagulant use for both appropriate indication and duration of therapy. Providing recommendations via chart review notes and alerting respective PCPs and CPPs results in veterans receiving safe and optimized care regarding their anticoagulation needs.