Heidi Splete

A new drug currently known as NG101 reduced nausea and vomiting in patients with obesity using GLP-1s by 40% and 67%, respectively, based on data from a phase 2 trial presented at the Obesity Society’s Obesity Week 2025 in Atlanta.

Previous research published in JAMA Network Open showed a nearly 65% discontinuation rate for three GLP-1s (liraglutide, semaglutide, or tirzepatide) among adults with overweight or obesity and without type 2 diabetes. Gastrointestinal (GI) side effects topped the list of reasons for dropping the medications.

Given the impact of nausea and vomiting on discontinuation, there is an unmet need for therapies to manage GI symptoms, said Kimberley Cummings, PhD, of Neurogastrx, Inc., in her presentation.

In the new study, Cummings and colleagues randomly assigned 90 adults aged 18-55 years with overweight or obesity (defined as a BMI ranging from 22.0 to 35.0) to receive a single subcutaneous dose of semaglutide (0.5 mg) plus 5 days of NG101 at 20 mg twice daily, or a placebo.

NG101 is a peripherally acting D2 antagonist designed to reduce nausea and vomiting associated with GLP-1 use, Cummings said. NG101 targets the nausea center of the brain but is peripherally restricted to prevent central nervous system side effects, she explained.

Compared with placebo, NG101 significantly reduced the incidence of nausea and vomiting by 40% and 67%, respectively. Use of NG101 also was associated with a significant reduction in the duration of nausea and vomiting; GI events lasting longer than 1 day were reported in 22% and 51% of the NG101 patients and placebo patients, respectively.

In addition, participants who received NG101 reported a 70% decrease in nausea severity from baseline.

Overall, patients in the NG101 group also reported significantly fewer adverse events than those in the placebo group (74 vs 135), suggesting an improved safety profile when semaglutide is administered in conjunction with NG101, the researchers noted. No serious adverse events related to the study drug were reported in either group.

The findings were limited by several factors including the relatively small sample size. Additional research is needed with other GLP-1 agonists in larger populations with longer follow-up periods, Cummings said. However, the results suggest that NG101 was safe and effectively improved side effects associated with GLP-1 agonists.

“We know there are receptors for GLP-1 in the area postrema (nausea center of the brain), and that NG101 works on this area to reduce nausea and vomiting, so the study findings were not unexpected,” said Jim O’Mara, president and CEO of Neurogastrx, in an interview.

The study was a single-dose study designed to show proof of concept, and future studies would involve treating patients going through the recommended titration schedule for their GLP-1s, O’Mara said. However, NG101 offers an opportunity to keep more patients on GLP-1 therapy and help them reach their long-term therapeutic goals, he said.

 

Decrease Side Effects for Weight-Loss Success

“GI side effects are often the rate-limiting step in implementing an effective medication that patients want to take but may not be able to tolerate,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for Weight and Diabetes Management, Burlington, Ontario, Canada, in an interview. “If we can decrease side effects, these medications could improve patients’ lives,” said Wharton, who was not involved in the study.

The improvement after a single dose of NG101 in patients receiving a single dose of semaglutide was impressive and in keeping with the mechanism of the drug action, said Wharton. “I was not surprised by the result but pleased that this single dose was shown to reduce the overall incidence of nausea and vomiting, the duration of nausea, the severity of nausea as rated by the study participants compared to placebo,” he said.

Ultimately, the clinical implications for NG101 are improved patient tolerance for GLP-1s and the ability to titrate and stay on them long term, incurring greater cardiometabolic benefit, Wharton told this news organization.

The current trial was limited to GLP1-1s on the market; newer medications may have fewer side effects, Wharton noted. “In clinical practice, patients often decrease the medication or titrate slower, and this could be the comparator,” he added.

The study was funded by Neurogastrx.

Wharton disclosed serving as a consultant for Neurogastrx but not as an investigator on the current study. He also reported having disclosed research on various GLP-1 medications.

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

A new drug currently known as NG101 reduced nausea and vomiting in patients with obesity using GLP-1s by 40% and 67%, respectively, based on data from a phase 2 trial presented at the Obesity Society’s Obesity Week 2025 in Atlanta.

Previous research published in JAMA Network Open showed a nearly 65% discontinuation rate for three GLP-1s (liraglutide, semaglutide, or tirzepatide) among adults with overweight or obesity and without type 2 diabetes. Gastrointestinal (GI) side effects topped the list of reasons for dropping the medications.

Given the impact of nausea and vomiting on discontinuation, there is an unmet need for therapies to manage GI symptoms, said Kimberley Cummings, PhD, of Neurogastrx, Inc., in her presentation.

In the new study, Cummings and colleagues randomly assigned 90 adults aged 18-55 years with overweight or obesity (defined as a BMI ranging from 22.0 to 35.0) to receive a single subcutaneous dose of semaglutide (0.5 mg) plus 5 days of NG101 at 20 mg twice daily, or a placebo.

NG101 is a peripherally acting D2 antagonist designed to reduce nausea and vomiting associated with GLP-1 use, Cummings said. NG101 targets the nausea center of the brain but is peripherally restricted to prevent central nervous system side effects, she explained.

Compared with placebo, NG101 significantly reduced the incidence of nausea and vomiting by 40% and 67%, respectively. Use of NG101 also was associated with a significant reduction in the duration of nausea and vomiting; GI events lasting longer than 1 day were reported in 22% and 51% of the NG101 patients and placebo patients, respectively.

In addition, participants who received NG101 reported a 70% decrease in nausea severity from baseline.

Overall, patients in the NG101 group also reported significantly fewer adverse events than those in the placebo group (74 vs 135), suggesting an improved safety profile when semaglutide is administered in conjunction with NG101, the researchers noted. No serious adverse events related to the study drug were reported in either group.

The findings were limited by several factors including the relatively small sample size. Additional research is needed with other GLP-1 agonists in larger populations with longer follow-up periods, Cummings said. However, the results suggest that NG101 was safe and effectively improved side effects associated with GLP-1 agonists.

“We know there are receptors for GLP-1 in the area postrema (nausea center of the brain), and that NG101 works on this area to reduce nausea and vomiting, so the study findings were not unexpected,” said Jim O’Mara, president and CEO of Neurogastrx, in an interview.

The study was a single-dose study designed to show proof of concept, and future studies would involve treating patients going through the recommended titration schedule for their GLP-1s, O’Mara said. However, NG101 offers an opportunity to keep more patients on GLP-1 therapy and help them reach their long-term therapeutic goals, he said.

 

Decrease Side Effects for Weight-Loss Success

“GI side effects are often the rate-limiting step in implementing an effective medication that patients want to take but may not be able to tolerate,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for Weight and Diabetes Management, Burlington, Ontario, Canada, in an interview. “If we can decrease side effects, these medications could improve patients’ lives,” said Wharton, who was not involved in the study.

The improvement after a single dose of NG101 in patients receiving a single dose of semaglutide was impressive and in keeping with the mechanism of the drug action, said Wharton. “I was not surprised by the result but pleased that this single dose was shown to reduce the overall incidence of nausea and vomiting, the duration of nausea, the severity of nausea as rated by the study participants compared to placebo,” he said.

Ultimately, the clinical implications for NG101 are improved patient tolerance for GLP-1s and the ability to titrate and stay on them long term, incurring greater cardiometabolic benefit, Wharton told this news organization.

The current trial was limited to GLP1-1s on the market; newer medications may have fewer side effects, Wharton noted. “In clinical practice, patients often decrease the medication or titrate slower, and this could be the comparator,” he added.

The study was funded by Neurogastrx.

Wharton disclosed serving as a consultant for Neurogastrx but not as an investigator on the current study. He also reported having disclosed research on various GLP-1 medications.

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

A new drug currently known as NG101 reduced nausea and vomiting in patients with obesity using GLP-1s by 40% and 67%, respectively, based on data from a phase 2 trial presented at the Obesity Society’s Obesity Week 2025 in Atlanta.

Previous research published in JAMA Network Open showed a nearly 65% discontinuation rate for three GLP-1s (liraglutide, semaglutide, or tirzepatide) among adults with overweight or obesity and without type 2 diabetes. Gastrointestinal (GI) side effects topped the list of reasons for dropping the medications.

Given the impact of nausea and vomiting on discontinuation, there is an unmet need for therapies to manage GI symptoms, said Kimberley Cummings, PhD, of Neurogastrx, Inc., in her presentation.

In the new study, Cummings and colleagues randomly assigned 90 adults aged 18-55 years with overweight or obesity (defined as a BMI ranging from 22.0 to 35.0) to receive a single subcutaneous dose of semaglutide (0.5 mg) plus 5 days of NG101 at 20 mg twice daily, or a placebo.

NG101 is a peripherally acting D2 antagonist designed to reduce nausea and vomiting associated with GLP-1 use, Cummings said. NG101 targets the nausea center of the brain but is peripherally restricted to prevent central nervous system side effects, she explained.

Compared with placebo, NG101 significantly reduced the incidence of nausea and vomiting by 40% and 67%, respectively. Use of NG101 also was associated with a significant reduction in the duration of nausea and vomiting; GI events lasting longer than 1 day were reported in 22% and 51% of the NG101 patients and placebo patients, respectively.

In addition, participants who received NG101 reported a 70% decrease in nausea severity from baseline.

Overall, patients in the NG101 group also reported significantly fewer adverse events than those in the placebo group (74 vs 135), suggesting an improved safety profile when semaglutide is administered in conjunction with NG101, the researchers noted. No serious adverse events related to the study drug were reported in either group.

The findings were limited by several factors including the relatively small sample size. Additional research is needed with other GLP-1 agonists in larger populations with longer follow-up periods, Cummings said. However, the results suggest that NG101 was safe and effectively improved side effects associated with GLP-1 agonists.

“We know there are receptors for GLP-1 in the area postrema (nausea center of the brain), and that NG101 works on this area to reduce nausea and vomiting, so the study findings were not unexpected,” said Jim O’Mara, president and CEO of Neurogastrx, in an interview.

The study was a single-dose study designed to show proof of concept, and future studies would involve treating patients going through the recommended titration schedule for their GLP-1s, O’Mara said. However, NG101 offers an opportunity to keep more patients on GLP-1 therapy and help them reach their long-term therapeutic goals, he said.

 

Decrease Side Effects for Weight-Loss Success

“GI side effects are often the rate-limiting step in implementing an effective medication that patients want to take but may not be able to tolerate,” said Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic for Weight and Diabetes Management, Burlington, Ontario, Canada, in an interview. “If we can decrease side effects, these medications could improve patients’ lives,” said Wharton, who was not involved in the study.

The improvement after a single dose of NG101 in patients receiving a single dose of semaglutide was impressive and in keeping with the mechanism of the drug action, said Wharton. “I was not surprised by the result but pleased that this single dose was shown to reduce the overall incidence of nausea and vomiting, the duration of nausea, the severity of nausea as rated by the study participants compared to placebo,” he said.

Ultimately, the clinical implications for NG101 are improved patient tolerance for GLP-1s and the ability to titrate and stay on them long term, incurring greater cardiometabolic benefit, Wharton told this news organization.

The current trial was limited to GLP1-1s on the market; newer medications may have fewer side effects, Wharton noted. “In clinical practice, patients often decrease the medication or titrate slower, and this could be the comparator,” he added.

The study was funded by Neurogastrx.

Wharton disclosed serving as a consultant for Neurogastrx but not as an investigator on the current study. He also reported having disclosed research on various GLP-1 medications.

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

Individuals who served in Iraq or Afghanistan had significantly higher rates of new-onset respiratory diseases after deployment compared to non-deployed control peers, based on data from more than 48,000 veterans. The findings were presented at the American College of Allergy, Asthma, and Immunology (ACAAI) 2025 Annual Meeting.

“Veterans deployed to Iraq and Afghanistan were often exposed to airborne hazards such as burn pits and dust storms,” said Patrick Gleeson, MD, an allergist at the University of Pennsylvania Perelman School of Medicine, Philadelphia, in a press release. 

“We found that these exposures may have long-term health impacts, particularly for respiratory diseases that can affect quality of life for years after service,” said Gleeson, who presented the results at the meeting.

Gleeson and colleagues used data from the Veterans Affairs Corporate Data Warehouse and Observational Medical Outcomes Partnership to identify veterans with a single deployment as part of Operation Iraqi Freedom or Operation Enduring Freedom. Participants had at least one outpatient visit prior to deployment with no baseline history of asthma, chronic rhinitis, chronic rhinosinusitis, or nasal polyposis. The mean age of the participants at deployment was 26.7 years, 84% were male, 75% were White, and 11% were Hispanic or Latino. Each was matched with a similar non-deployed veteran control.

The primary outcome was outpatient diagnoses or problem list entries for asthma, chronic rhinitis, chronic rhinosinusitis, or nasal polyposis.

Compared to non-deployed peers, deployed veterans had a 55% increased risk of asthma, a 48% increased risk of nasal polyposis, a 41% increased risk of chronic rhinitis, and a 27% increased risk of chronic rhinosinusitis, based on Cox proportional hazards models (P < .0005 for all).

The findings were limited by the retrospective design. However, “Recognizing the link between deployment and respiratory disease can help guide medical support, policy, and preventive strategies for those affected,” Gleeson said in the press release. 

The study received no outside funding. The researchers disclosed no financial conflicts of interest.

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

Individuals who served in Iraq or Afghanistan had significantly higher rates of new-onset respiratory diseases after deployment compared to non-deployed control peers, based on data from more than 48,000 veterans. The findings were presented at the American College of Allergy, Asthma, and Immunology (ACAAI) 2025 Annual Meeting.

“Veterans deployed to Iraq and Afghanistan were often exposed to airborne hazards such as burn pits and dust storms,” said Patrick Gleeson, MD, an allergist at the University of Pennsylvania Perelman School of Medicine, Philadelphia, in a press release. 

“We found that these exposures may have long-term health impacts, particularly for respiratory diseases that can affect quality of life for years after service,” said Gleeson, who presented the results at the meeting.

Gleeson and colleagues used data from the Veterans Affairs Corporate Data Warehouse and Observational Medical Outcomes Partnership to identify veterans with a single deployment as part of Operation Iraqi Freedom or Operation Enduring Freedom. Participants had at least one outpatient visit prior to deployment with no baseline history of asthma, chronic rhinitis, chronic rhinosinusitis, or nasal polyposis. The mean age of the participants at deployment was 26.7 years, 84% were male, 75% were White, and 11% were Hispanic or Latino. Each was matched with a similar non-deployed veteran control.

The primary outcome was outpatient diagnoses or problem list entries for asthma, chronic rhinitis, chronic rhinosinusitis, or nasal polyposis.

Compared to non-deployed peers, deployed veterans had a 55% increased risk of asthma, a 48% increased risk of nasal polyposis, a 41% increased risk of chronic rhinitis, and a 27% increased risk of chronic rhinosinusitis, based on Cox proportional hazards models (P < .0005 for all).

The findings were limited by the retrospective design. However, “Recognizing the link between deployment and respiratory disease can help guide medical support, policy, and preventive strategies for those affected,” Gleeson said in the press release. 

The study received no outside funding. The researchers disclosed no financial conflicts of interest.

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

Individuals who served in Iraq or Afghanistan had significantly higher rates of new-onset respiratory diseases after deployment compared to non-deployed control peers, based on data from more than 48,000 veterans. The findings were presented at the American College of Allergy, Asthma, and Immunology (ACAAI) 2025 Annual Meeting.

“Veterans deployed to Iraq and Afghanistan were often exposed to airborne hazards such as burn pits and dust storms,” said Patrick Gleeson, MD, an allergist at the University of Pennsylvania Perelman School of Medicine, Philadelphia, in a press release. 

“We found that these exposures may have long-term health impacts, particularly for respiratory diseases that can affect quality of life for years after service,” said Gleeson, who presented the results at the meeting.

Gleeson and colleagues used data from the Veterans Affairs Corporate Data Warehouse and Observational Medical Outcomes Partnership to identify veterans with a single deployment as part of Operation Iraqi Freedom or Operation Enduring Freedom. Participants had at least one outpatient visit prior to deployment with no baseline history of asthma, chronic rhinitis, chronic rhinosinusitis, or nasal polyposis. The mean age of the participants at deployment was 26.7 years, 84% were male, 75% were White, and 11% were Hispanic or Latino. Each was matched with a similar non-deployed veteran control.

The primary outcome was outpatient diagnoses or problem list entries for asthma, chronic rhinitis, chronic rhinosinusitis, or nasal polyposis.

Compared to non-deployed peers, deployed veterans had a 55% increased risk of asthma, a 48% increased risk of nasal polyposis, a 41% increased risk of chronic rhinitis, and a 27% increased risk of chronic rhinosinusitis, based on Cox proportional hazards models (P < .0005 for all).

The findings were limited by the retrospective design. However, “Recognizing the link between deployment and respiratory disease can help guide medical support, policy, and preventive strategies for those affected,” Gleeson said in the press release. 

The study received no outside funding. The researchers disclosed no financial conflicts of interest.

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

The benefits of many elective nonhepatic surgeries outweigh the risks for select patients with compensated cirrhosis, but those at high risk for poor surgical outcomes should continue to seek alternatives to surgery, according to an updated guideline from the American College of Gastroenterology.

Procedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology. 

“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.

“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.

The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.

Three conditional recommendations:

• For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
• For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
• For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.

The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis. 

 

What’s New and Notable?

New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.

The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.

Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.

“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.

These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.

 

Tackling Clinical Challenges

The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.

“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.

“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.

For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.

The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose. 

 

A version of this article appeared on Medscape.com

The benefits of many elective nonhepatic surgeries outweigh the risks for select patients with compensated cirrhosis, but those at high risk for poor surgical outcomes should continue to seek alternatives to surgery, according to an updated guideline from the American College of Gastroenterology.

Procedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology. 

“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.

“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.

The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.

Three conditional recommendations:

• For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
• For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
• For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.

The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis. 

 

What’s New and Notable?

New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.

The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.

Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.

“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.

These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.

 

Tackling Clinical Challenges

The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.

“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.

“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.

For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.

The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose. 

 

A version of this article appeared on Medscape.com

The benefits of many elective nonhepatic surgeries outweigh the risks for select patients with compensated cirrhosis, but those at high risk for poor surgical outcomes should continue to seek alternatives to surgery, according to an updated guideline from the American College of Gastroenterology.

Procedures such as cholecystectomy and hernia repair can be safely performed if precautions are taken, but surgical decision-making in patients with cirrhosis calls for a nuanced approach that takes into account several factors, including severity of liver disease, nonhepatic comorbidities, and procedure-specific considerations, wrote lead author Nadim Mahmud, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine, University of Pennsylvania, Philadelphia, and colleagues, in the American Journal of Gastroenterology. 

“Patients with cirrhosis face substantially higher risks from surgery than those without liver disease, and careful guidance and risk stratification are essential,” Mahmud told GI & Hepatology News.

“At the same time, more patients are living longer with cirrhosis and increasingly require nonhepatic surgeries. Clinicians need up-to-date, practical recommendations that go beyond liver scores alone by integrating liver disease severity, comorbidities, and procedure-specific risk,” Mahmud said. The new guideline provides a comprehensive framework to help ensure that patients with cirrhosis undergo necessary operations, while managing preventable complications, he explained.

The guideline includes four recommendations for preoperative care, of which three are conditional and one is strong. The strong recommendation calls for the use of thrombopoietin receptor agonists, dosed according to baseline platelet count, in patients with cirrhosis and severe thrombocytopenia who are undergoing invasive procedures to reduce the need for perioperative transfusions and potentially reduce the risk for periprocedural bleeding.

Three conditional recommendations:

• For patients with compensated cirrhosis and unclear presence of clinically significant portal hypertension (CSPH), preoperative liver stiffness measurement and platelet count assessment are recommended to determine whether CSPH is present due to increased perioperative risks associated with the condition. Cross-sectional imaging should be conducted to identify portosystemic collaterals and complications of portal hypertension.
• For patients with cirrhosis and CSPH with alternative indications for transjugular intrahepatic portosystemic shunt (TIPS), such as large varices or refractory ascites, preoperative TIPS is suggested to reduce postoperative morbidity and mortality attributable to portal hypertension.
• For patients with cirrhosis undergoing major hepatic surgery, referral to a high-volume liver surgery or transplant center, when feasible, is recommended.

The guideline also advises on 26 key concepts, including nutrition, alcohol and tobacco use, comorbidities such as frailty and sarcopenia, and preoperative treatment of liver disease drivers such as hepatitis B, hepatitis C, and autoimmune hepatitis. 

 

What’s New and Notable?

New elements of the guideline include use of cirrhosis-specific risk calculators, especially the Veterans Outcomes and Costs Associated with Liver disease (VOCAL)-Penn Score, to estimate operative risk and facilitate shared decision-making regarding surgery. The VOCAL-Penn Score, developed by Mahmud and colleagues at the University of Pennsylvania, incorporates surgery type and has shown superiority to older tools that often overestimate risk, Mahmud told GI & Hepatology News.

The guideline highlights standardized assessment of portal hypertension using noninvasive liver stiffness measurement plus platelet count and imaging, Mahmud said. “The guideline also underscores the importance of considering liver transplant evaluation before surgery in higher-risk patients,” he noted.

Clinicians will find clear recommendations on optimizing the perioperative period through nutritional support and structured prehabilitation, as well as the use of viscoelastic testing to guide transfusion decisions and the use of thrombopoietin-receptor agonists for severe thrombocytopenia, he added.

“Importantly, in carefully selected patients with significant portal hypertension, a preoperative transjugular intrahepatic portosystemic shunt may be reasonable, though it is not recommended broadly,” Mahmud said. “Finally, procedure-specific guidance, such as elective hernia repair after ascites control, laparoscopic cholecystectomy in well-compensated cirrhosis, and sleeve gastrectomy as the bariatric procedure of choice, helps translate risk into action,” he said.

These elements address key challenges in managing perioperative risk in patients with cirrhosis, namely miscalibrated risk estimates, inconsistent portal hypertension assessment, hemostasis management, and wide variation in practice, Mahmud noted.

 

Tackling Clinical Challenges

The new guideline collates the latest evidence and assessment tools to provide practical advice for clinicians to not only estimate risk but also better prepare patients with cirrhosis for surgical procedures, Peter D. Block, MD, assistant professor of medicine in the section of digestive diseases at the Yale School of Medicine, New Haven, Connecticut, told GI & Hepatology News.

“The larger and more invasive the operation, the higher the risk,” said Block, who was not involved in writing the guideline. Surgeries associated with the highest risk for patients with cirrhosis include major open abdominal operations, chest or cardiothoracic surgery, and major vascular surgeries, as well as emergency operations, for which there is less time to optimize any liver-related problems in advance, he said.

“Cirrhosis affects clotting, fluid balance, immunity, kidney function, and medication clearance, and each of these factors influence surgical risk,” Block said. “The guideline recommends combining liver-specific risk assessment scores with surgery-specific factors and clinical judgement, rather than relying on a single test,” he noted.

For elective surgeries, “the guideline provides practical pathways for when and how to optimize first, and when surgery must proceed despite higher risk,” he said.

The guideline was supported by the American College of Gastroenterology. Mahmud disclosed receiving research support from the National Institute of Diabetes and Digestive and Kidney Diseases and investigator-initiated research funding from Grifols, unrelated to the guideline. Block had no financial conflicts to disclose. 

 

A version of this article appeared on Medscape.com

DENVER – Standard intact protein formulas (SPFs) significantly increased the risk for gastrointestinal complications in premature infants compared to extensively hydrolyzed formulas (eHFs), according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.

Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.

The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.

Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.

Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.

Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis. 

Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.

The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.

Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.

 

Younger Babies at Greater Risk

Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.

“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.

“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.

The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.

Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.

However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.

Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.

The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

DENVER – Standard intact protein formulas (SPFs) significantly increased the risk for gastrointestinal complications in premature infants compared to extensively hydrolyzed formulas (eHFs), according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.

Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.

The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.

Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.

Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.

Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis. 

Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.

The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.

Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.

 

Younger Babies at Greater Risk

Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.

“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.

“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.

The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.

Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.

However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.

Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.

The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

DENVER – Standard intact protein formulas (SPFs) significantly increased the risk for gastrointestinal complications in premature infants compared to extensively hydrolyzed formulas (eHFs), according to new data presented at the American Academy of Pediatrics (AAP) 2025 National Conference & Exhibition.

Necrotizing enterocolitis (NEC) can affect the intestinal wall of neonates, with potentially life-threatening results. The inflammatory condition is characterized by feeding intolerance, rectal bleeding, and bowel perforations, said presenting author Puja Kulkarni, medical student at California Northstate University College of Medicine, Elk Grove, California, and colleagues.

The etiology of NEC remains unclear, but previous research suggests that formula feeding may play a role, the researchers said. “NEC remains a leading cause of morbidity and mortality in premature infants, yet there is still no clear consensus on the optimal feeding strategy to reduce risk,” Kulkarni said in an interview with GI & Hepatology News.

Most hospital guidelines call for solely using SPFs in NICUs, especially in cases where maternal breast milk is not available, said Kulkarni. Therefore, “it was critical to investigate whether different types of formula, such as extensively hydrolyzed formula, could influence the incidence of NEC,” she said.

Kulkarni and colleagues conducted a literature search and identified three randomized, controlled trials that compared eHFs to SPFs in a study population of 1180 premature infants.

Overall, infants who received SPFs had a significantly greater risk for both NEC and feeding intolerance than those who received eHFs, with odds ratios of 2.54 and 2.87, respectively, and these associations remained after a sensitivity analysis. 

Other research, such as the German Infant Nutritional Intervention (GINI) study, has shown similar results regarding the effect of formula type on childhood pathologies, Kulkarni noted. The GINI study showed that HFs can help prevent the development of allergic diseases in children with a family history of allergies, she said.

The results of the current analysis suggest a significantly increased risk for NEC, as well as feeding intolerance, which can be a precursor to NEC, in premature infants fed SPFs compared to those fed eHFs, said Kulkarni. “If validated by further research, this could lead to changes in NICU feeding protocols, especially in situations where donor breast milk is not available. Clinicians may want to consider the type of protein in formula as an important factor in NEC prevention,” she said. The current findings support the need for more research into the effects of formula throughout the infant and childhood years.

Additional studies are needed to validate the findings in larger, multicenter cohorts to ensure generalizability, especially in the US, where current guidelines favor SPFs based on limited data, said Kulkarni. Much of the research in the US has been conducted by the formula companies themselves, and she and her colleagues took this risk for bias into account in their meta-analysis.

 

Younger Babies at Greater Risk

Documented rates of NEC have remained stable or decreased slightly over the past 20 years, which supports the need for research on prevention and early identification, as well as effective medical treatment, said Catherine Haut, DNP, CPNP-AC/PC, in an interview.

“With improved neonatal intensive care, younger neonates are surviving, but these babies also have a higher risk of development of NEC,” said Haut, director of nursing research and evidence-based practice at Nemours Children’s Health, Delaware, New Jersey, who was not involved in the study.

“Historically, NEC has been related to feeding, among other variables, but the use of more specific or standardized feeding methods including increased use of human milk in very low-birth weight infants has resulted in better outcomes,” she said.

The finding from the current meta-analysis that the use of SPFs poses a higher risk for NEC than the use of eHFs was not unexpected, Haut told GI & Hepatology News. Some infants are allergic to cow’s milk, and replacing this type of formula with eHF is the recommended treatment as these formulas incorporate proteins which are more easily digested, she said.

Systematic reviews and meta-analyses are considered high levels of evidence, and the current study’s documentation of the benefits of eHF could help decrease the rate of NEC in premature infants, Haut said. “Despite a higher cost associated with eHF, in formula-fed preterm neonates, there would be benefit to using eHF vs risk of standard protein formulas,” she said.

However, the current study represents a very small population compared to the total number of infants born at less than 37 weeks’ gestation, which is reported to be 10% of all newborns in the US each year, Haut noted.

Additional large studies, including randomized control trials, are needed to further document the effects of using eHF in very young premature infants and potentially help reduce the incidence of NEC in this population, she said.

The study received no outside funding. The researchers and Haut had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

Early-onset gastrointestinal (GI) cancers are climbing among those younger than 50 years, in the US and globally. Although colorectal cancer accounts for approximately half of such cases, rates are also increasing for gastric, esophageal, pancreatic, and several rarer GI malignancies.

Because most in this age group are not included in screening protocols and may present with vague symptoms, diagnosis and treatment is frequently delayed. According to experts in the field, counteracting this trend requires establishing a lower threshold for evaluation, attention to modifiable risk factors, and embracing emerging noninvasive diagnostic tools.

 

Diagnostic Dilemmas

“Colorectal cancer in particular is often diagnosed later in life,” said Nicholas DeVito, MD, assistant professor at Duke University Medical Center, Durham, North Carolina, and a specialist in GI malignancies. “When the patient is too young for routine screening colonoscopy (< 45 years), they aren’t screened at all, they do not have alarming symptoms, or their symptoms are overlooked.” Other increasingly common GI cancers in young people (esophageal, gastric, pancreatic) lack routine screening guidelines due to limited evidence, he added.

Symptoms such as nausea, weight loss, upset stomach, and abdominal pain are often nonspecific and have many other potential causes, so GI cancers may not be high on the list of possible diagnoses in patients younger than 50 years, said DeVito.

“Insurance coverage, socioeconomic status, appointment availability, and awareness of symptoms and screening methods are all barriers to diagnosis as well, which affect the diagnostic timeline of many cancers,” he added.“While there are multiple factors that contribute to a cancer diagnosis, it seems that obesity, a Western diet, a sedentary lifestyle are all major contributors to the rise in early GI cancers,” DeVito told GI & Hepatology News. “There is no blame or judgement to go around as cancer can happen to anyone at any time, with none of these factors present,” he emphasized.

When counseling patients about GI cancer risk, DeVito recommends keeping advice simple and specific. In general, they should restrict red meat to once a week, emphasize fresh fruits and vegetables, cap alcohol to ≤ 1 serving per day, and limit ultraprocessed foods (e.g., packaged snacks, preprepared meals, and sugary beverages).

Exercise is another pillar. “Find an activity you enjoy and work toward 30 minutes of aerobic exercise three times a week,” he advised. He also encourages finding opportunities to incorporate physical activity in daily lives, such as using a standing desk at work, while keeping patients’ socioeconomic constraints in mind.

Evidence around GI cancer prevention interventions is still evolving. However, a randomized phase 3 trial presented at American Society of Clinical Oncology’s 2025 meeting found significant improvement in disease-free survival among adults with resected stage III or high-risk stage II colon cancer (median age, 61 years) who reported higher intake of anti-inflammatory foods and greater exercise than a comparator group.

“In general, clinicians should be aware of the risk factors, make referrals to physical therapy, weight-loss specialists, endocrinologists, and nutritionists when appropriate, and be consistent and clear with patients about recommendations and what’s achievable,” DeVito said. “Meeting patients where they are can help make incremental progress, as these interventions take time and patience, and we should be understanding of that.” 

Identifying at-risk younger adults goes beyond discussing family history and obesity to include diet, exercise, and daily lifestyle, he added.

“Symptoms of potential GI cancer need to be taken seriously in all patients, and there should be a lower threshold in 2025 to get a colonoscopy, endoscopy, or CT scan than in previous years given all that we know today. We then need to establish through clinical studies who needs screening tests and who doesn’t, and what interventions work best to reduce risk.” 

 

Vigilance in the Absence of Screening

“Most GI cancers, unfortunately, can grow a fair amount before symptoms arise, so many patients present with symptoms only when a tumor has grown enough to affect organ function,” said Miguel Burch, MD, chief of minimally invasive and GI surgery at Cedars-Sinai Medical Center, Los Angeles.

Early screening improves outcomes in gastric cancer, Burch noted, and survival benefits are reflected in several East Asian countries that offer gastric cancer screening starting at age 40. In one study from Korea, a single upper endoscopy was associated with an approximate 40% reduction in gastric cancer mortality compared with no screening.

In the US, lack of funding for GI cancer screening remains a barrier to early identification, Burch emphasized. The impact is wide-ranging, contributing to increased morbidity and mortality in younger adults often in their most productive years, leading to lost wages and emotional strains upon patients and their families.Routine endoscopic or imaging screening is not typically performed in the US, and newer blood-based tests such as circulating tumor DNA are not yet sensitive enough to reliably detect very early-stage disease. Nonetheless, there is evidence that noninvasive biomarkers could soon help expand GI cancer screening.

In a study published in JAMA Surgery, Sui and colleagues tested a 10-microRNA signature assay (Destinex) for early detection of gastric cancer and reported robust identification rates above 95%.

“In recent years, the liquid biopsy has gained momentum with the hope of augmenting cancer detection from peripheral blood, even indicating potential as a screening test for healthy populations,” wrote Max R. Coffey, MD, and Vivian E. Strong, MD, both of the Memorial Sloan Kettering Cancer Center in New York City, in an accompanying editorial.

“Early detection is absolutely critical; when gastric cancer is found early, outcomes are dramatically better,” Strong told GI & Hepatology News. Subtle symptoms — reflux, persistent GI discomfort, or unexplained weight loss — should never be ignored, she added.

Early detection should also focus on additional risk factors such as prior Helicobacter pylori infection, smoking, and family history.

“Anyone with a personal or family history of H pylori should have very careful follow-up, and if one household member tests positive, all should be checked,” Strong said. “Just as importantly, if one or more family members have had stomach cancer, that should be discussed with a healthcare provider, as it may warrant higher-level surveillance and genetic testing.” 

Individuals concerned about increased risk for GI cancer should proactively ask their doctors whether they might benefit from testing or surveillance, Strong added.

“Lifestyle changes, timely medical evaluation, and tailored surveillance all play a vital role in prevention.”

DeVito disclosed clinical trial funding from the Gateway foundation, Xilio, Phanes, Astellas, GSK, as well as consulting fees/advisory board participation for Guardant, Agenus, and Xilio. Strong disclosed speaking honoraria for Merck and Astra Zeneca.

The study by Sui and colleagues was supported by the National Cancer Institute, National Institutes of Health, as well as by a grant from the American Gastroenterological Association Robert & Sally Funderburg Research Award in Gastric Cancer, and the Stupid Strong Foundation.

Burch had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

Early-onset gastrointestinal (GI) cancers are climbing among those younger than 50 years, in the US and globally. Although colorectal cancer accounts for approximately half of such cases, rates are also increasing for gastric, esophageal, pancreatic, and several rarer GI malignancies.

Because most in this age group are not included in screening protocols and may present with vague symptoms, diagnosis and treatment is frequently delayed. According to experts in the field, counteracting this trend requires establishing a lower threshold for evaluation, attention to modifiable risk factors, and embracing emerging noninvasive diagnostic tools.

 

Diagnostic Dilemmas

“Colorectal cancer in particular is often diagnosed later in life,” said Nicholas DeVito, MD, assistant professor at Duke University Medical Center, Durham, North Carolina, and a specialist in GI malignancies. “When the patient is too young for routine screening colonoscopy (< 45 years), they aren’t screened at all, they do not have alarming symptoms, or their symptoms are overlooked.” Other increasingly common GI cancers in young people (esophageal, gastric, pancreatic) lack routine screening guidelines due to limited evidence, he added.

Symptoms such as nausea, weight loss, upset stomach, and abdominal pain are often nonspecific and have many other potential causes, so GI cancers may not be high on the list of possible diagnoses in patients younger than 50 years, said DeVito.

“Insurance coverage, socioeconomic status, appointment availability, and awareness of symptoms and screening methods are all barriers to diagnosis as well, which affect the diagnostic timeline of many cancers,” he added.“While there are multiple factors that contribute to a cancer diagnosis, it seems that obesity, a Western diet, a sedentary lifestyle are all major contributors to the rise in early GI cancers,” DeVito told GI & Hepatology News. “There is no blame or judgement to go around as cancer can happen to anyone at any time, with none of these factors present,” he emphasized.

When counseling patients about GI cancer risk, DeVito recommends keeping advice simple and specific. In general, they should restrict red meat to once a week, emphasize fresh fruits and vegetables, cap alcohol to ≤ 1 serving per day, and limit ultraprocessed foods (e.g., packaged snacks, preprepared meals, and sugary beverages).

Exercise is another pillar. “Find an activity you enjoy and work toward 30 minutes of aerobic exercise three times a week,” he advised. He also encourages finding opportunities to incorporate physical activity in daily lives, such as using a standing desk at work, while keeping patients’ socioeconomic constraints in mind.

Evidence around GI cancer prevention interventions is still evolving. However, a randomized phase 3 trial presented at American Society of Clinical Oncology’s 2025 meeting found significant improvement in disease-free survival among adults with resected stage III or high-risk stage II colon cancer (median age, 61 years) who reported higher intake of anti-inflammatory foods and greater exercise than a comparator group.

“In general, clinicians should be aware of the risk factors, make referrals to physical therapy, weight-loss specialists, endocrinologists, and nutritionists when appropriate, and be consistent and clear with patients about recommendations and what’s achievable,” DeVito said. “Meeting patients where they are can help make incremental progress, as these interventions take time and patience, and we should be understanding of that.” 

Identifying at-risk younger adults goes beyond discussing family history and obesity to include diet, exercise, and daily lifestyle, he added.

“Symptoms of potential GI cancer need to be taken seriously in all patients, and there should be a lower threshold in 2025 to get a colonoscopy, endoscopy, or CT scan than in previous years given all that we know today. We then need to establish through clinical studies who needs screening tests and who doesn’t, and what interventions work best to reduce risk.” 

 

Vigilance in the Absence of Screening

“Most GI cancers, unfortunately, can grow a fair amount before symptoms arise, so many patients present with symptoms only when a tumor has grown enough to affect organ function,” said Miguel Burch, MD, chief of minimally invasive and GI surgery at Cedars-Sinai Medical Center, Los Angeles.

Early screening improves outcomes in gastric cancer, Burch noted, and survival benefits are reflected in several East Asian countries that offer gastric cancer screening starting at age 40. In one study from Korea, a single upper endoscopy was associated with an approximate 40% reduction in gastric cancer mortality compared with no screening.

In the US, lack of funding for GI cancer screening remains a barrier to early identification, Burch emphasized. The impact is wide-ranging, contributing to increased morbidity and mortality in younger adults often in their most productive years, leading to lost wages and emotional strains upon patients and their families.Routine endoscopic or imaging screening is not typically performed in the US, and newer blood-based tests such as circulating tumor DNA are not yet sensitive enough to reliably detect very early-stage disease. Nonetheless, there is evidence that noninvasive biomarkers could soon help expand GI cancer screening.

In a study published in JAMA Surgery, Sui and colleagues tested a 10-microRNA signature assay (Destinex) for early detection of gastric cancer and reported robust identification rates above 95%.

“In recent years, the liquid biopsy has gained momentum with the hope of augmenting cancer detection from peripheral blood, even indicating potential as a screening test for healthy populations,” wrote Max R. Coffey, MD, and Vivian E. Strong, MD, both of the Memorial Sloan Kettering Cancer Center in New York City, in an accompanying editorial.

“Early detection is absolutely critical; when gastric cancer is found early, outcomes are dramatically better,” Strong told GI & Hepatology News. Subtle symptoms — reflux, persistent GI discomfort, or unexplained weight loss — should never be ignored, she added.

Early detection should also focus on additional risk factors such as prior Helicobacter pylori infection, smoking, and family history.

“Anyone with a personal or family history of H pylori should have very careful follow-up, and if one household member tests positive, all should be checked,” Strong said. “Just as importantly, if one or more family members have had stomach cancer, that should be discussed with a healthcare provider, as it may warrant higher-level surveillance and genetic testing.” 

Individuals concerned about increased risk for GI cancer should proactively ask their doctors whether they might benefit from testing or surveillance, Strong added.

“Lifestyle changes, timely medical evaluation, and tailored surveillance all play a vital role in prevention.”

DeVito disclosed clinical trial funding from the Gateway foundation, Xilio, Phanes, Astellas, GSK, as well as consulting fees/advisory board participation for Guardant, Agenus, and Xilio. Strong disclosed speaking honoraria for Merck and Astra Zeneca.

The study by Sui and colleagues was supported by the National Cancer Institute, National Institutes of Health, as well as by a grant from the American Gastroenterological Association Robert & Sally Funderburg Research Award in Gastric Cancer, and the Stupid Strong Foundation.

Burch had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

Early-onset gastrointestinal (GI) cancers are climbing among those younger than 50 years, in the US and globally. Although colorectal cancer accounts for approximately half of such cases, rates are also increasing for gastric, esophageal, pancreatic, and several rarer GI malignancies.

Because most in this age group are not included in screening protocols and may present with vague symptoms, diagnosis and treatment is frequently delayed. According to experts in the field, counteracting this trend requires establishing a lower threshold for evaluation, attention to modifiable risk factors, and embracing emerging noninvasive diagnostic tools.

 

Diagnostic Dilemmas

“Colorectal cancer in particular is often diagnosed later in life,” said Nicholas DeVito, MD, assistant professor at Duke University Medical Center, Durham, North Carolina, and a specialist in GI malignancies. “When the patient is too young for routine screening colonoscopy (< 45 years), they aren’t screened at all, they do not have alarming symptoms, or their symptoms are overlooked.” Other increasingly common GI cancers in young people (esophageal, gastric, pancreatic) lack routine screening guidelines due to limited evidence, he added.

Symptoms such as nausea, weight loss, upset stomach, and abdominal pain are often nonspecific and have many other potential causes, so GI cancers may not be high on the list of possible diagnoses in patients younger than 50 years, said DeVito.

“Insurance coverage, socioeconomic status, appointment availability, and awareness of symptoms and screening methods are all barriers to diagnosis as well, which affect the diagnostic timeline of many cancers,” he added.“While there are multiple factors that contribute to a cancer diagnosis, it seems that obesity, a Western diet, a sedentary lifestyle are all major contributors to the rise in early GI cancers,” DeVito told GI & Hepatology News. “There is no blame or judgement to go around as cancer can happen to anyone at any time, with none of these factors present,” he emphasized.

When counseling patients about GI cancer risk, DeVito recommends keeping advice simple and specific. In general, they should restrict red meat to once a week, emphasize fresh fruits and vegetables, cap alcohol to ≤ 1 serving per day, and limit ultraprocessed foods (e.g., packaged snacks, preprepared meals, and sugary beverages).

Exercise is another pillar. “Find an activity you enjoy and work toward 30 minutes of aerobic exercise three times a week,” he advised. He also encourages finding opportunities to incorporate physical activity in daily lives, such as using a standing desk at work, while keeping patients’ socioeconomic constraints in mind.

Evidence around GI cancer prevention interventions is still evolving. However, a randomized phase 3 trial presented at American Society of Clinical Oncology’s 2025 meeting found significant improvement in disease-free survival among adults with resected stage III or high-risk stage II colon cancer (median age, 61 years) who reported higher intake of anti-inflammatory foods and greater exercise than a comparator group.

“In general, clinicians should be aware of the risk factors, make referrals to physical therapy, weight-loss specialists, endocrinologists, and nutritionists when appropriate, and be consistent and clear with patients about recommendations and what’s achievable,” DeVito said. “Meeting patients where they are can help make incremental progress, as these interventions take time and patience, and we should be understanding of that.” 

Identifying at-risk younger adults goes beyond discussing family history and obesity to include diet, exercise, and daily lifestyle, he added.

“Symptoms of potential GI cancer need to be taken seriously in all patients, and there should be a lower threshold in 2025 to get a colonoscopy, endoscopy, or CT scan than in previous years given all that we know today. We then need to establish through clinical studies who needs screening tests and who doesn’t, and what interventions work best to reduce risk.” 

 

Vigilance in the Absence of Screening

“Most GI cancers, unfortunately, can grow a fair amount before symptoms arise, so many patients present with symptoms only when a tumor has grown enough to affect organ function,” said Miguel Burch, MD, chief of minimally invasive and GI surgery at Cedars-Sinai Medical Center, Los Angeles.

Early screening improves outcomes in gastric cancer, Burch noted, and survival benefits are reflected in several East Asian countries that offer gastric cancer screening starting at age 40. In one study from Korea, a single upper endoscopy was associated with an approximate 40% reduction in gastric cancer mortality compared with no screening.

In the US, lack of funding for GI cancer screening remains a barrier to early identification, Burch emphasized. The impact is wide-ranging, contributing to increased morbidity and mortality in younger adults often in their most productive years, leading to lost wages and emotional strains upon patients and their families.Routine endoscopic or imaging screening is not typically performed in the US, and newer blood-based tests such as circulating tumor DNA are not yet sensitive enough to reliably detect very early-stage disease. Nonetheless, there is evidence that noninvasive biomarkers could soon help expand GI cancer screening.

In a study published in JAMA Surgery, Sui and colleagues tested a 10-microRNA signature assay (Destinex) for early detection of gastric cancer and reported robust identification rates above 95%.

“In recent years, the liquid biopsy has gained momentum with the hope of augmenting cancer detection from peripheral blood, even indicating potential as a screening test for healthy populations,” wrote Max R. Coffey, MD, and Vivian E. Strong, MD, both of the Memorial Sloan Kettering Cancer Center in New York City, in an accompanying editorial.

“Early detection is absolutely critical; when gastric cancer is found early, outcomes are dramatically better,” Strong told GI & Hepatology News. Subtle symptoms — reflux, persistent GI discomfort, or unexplained weight loss — should never be ignored, she added.

Early detection should also focus on additional risk factors such as prior Helicobacter pylori infection, smoking, and family history.

“Anyone with a personal or family history of H pylori should have very careful follow-up, and if one household member tests positive, all should be checked,” Strong said. “Just as importantly, if one or more family members have had stomach cancer, that should be discussed with a healthcare provider, as it may warrant higher-level surveillance and genetic testing.” 

Individuals concerned about increased risk for GI cancer should proactively ask their doctors whether they might benefit from testing or surveillance, Strong added.

“Lifestyle changes, timely medical evaluation, and tailored surveillance all play a vital role in prevention.”

DeVito disclosed clinical trial funding from the Gateway foundation, Xilio, Phanes, Astellas, GSK, as well as consulting fees/advisory board participation for Guardant, Agenus, and Xilio. Strong disclosed speaking honoraria for Merck and Astra Zeneca.

The study by Sui and colleagues was supported by the National Cancer Institute, National Institutes of Health, as well as by a grant from the American Gastroenterological Association Robert & Sally Funderburg Research Award in Gastric Cancer, and the Stupid Strong Foundation.

Burch had no financial conflicts to disclose.

 

A version of this article appeared on Medscape.com.

A new $100 million pilot program launched by the Department of Health and Human Services (HHS) offers state and community-based health care organizations the resources for prevention, testing, and treatment of hepatitis C among individuals with substance use disorder and serious mental illness, according to an HHS press release.

The program, known as the Hepatitis C Elimination Initiative Pilot, will be administered by the Substance and Mental Health Administration. “This program is designed to support communities severely affected by homelessness and to gain insights on effective ways to identify patients, complete treatment, cure infections, and reduce reinfection by hepatitis C,” according to the press release.

The upfront investment in hepatitis C management is projected to not only save lives, but also to save community health care costs in the long-term, according to the press release.

“This is a vigorous pilot program that provides the first steps toward the large goal of eliminating hepatitis C in the United States population,” said William Schaffner, MD, professor of infectious diseases at Vanderbilt University Medical Center, Nashville, Tennessee, in an interview.

Hepatitis C affects more than two million individuals in the US, and is often complicated by social and medical issues such as homelessness, substance abuse, and mental health issues, said Schaffner. Fortunately, hepatitis C can be treated with oral medications that cure the chronic viral infection, thereby ending ongoing liver injury and interrupting person-to-person transmission of the virus by sharing needles, he said.

Given that the population most affected with hepatitis C also is often homeless, with possible mental health issues and sharing of needles for illicit drug use, challenges in reaching this population include assuring them that the care they receive though this and other programs is nonjudgemental and helpful, Schaffner told GI & Hepatology News.

The oral medications that now can cure the chronic hepatitis C viral infections must be taken over a period of weeks, and patients who lead socially disorganized lives often need assistance to assure that the medicine is taken as intended, so trained and sensitive personnel who are committed to helping this population are needed to make treatment programs succeed, he said.

Looking ahead, “the purpose of the pilot studies that will be funded by this program is to explore various approaches to determine which are more successful in bringing patients in to be evaluated and then to complete treatment,” Schaffner added.

State and community-based organizations are among the entities eligible to apply for the program. Potential applicants can find information about the program and application materials on the SAMSHA website.

Schaffner had no financial conflicts to disclose.

A version of this article appeared on Medscape.com . 

A new $100 million pilot program launched by the Department of Health and Human Services (HHS) offers state and community-based health care organizations the resources for prevention, testing, and treatment of hepatitis C among individuals with substance use disorder and serious mental illness, according to an HHS press release.

The program, known as the Hepatitis C Elimination Initiative Pilot, will be administered by the Substance and Mental Health Administration. “This program is designed to support communities severely affected by homelessness and to gain insights on effective ways to identify patients, complete treatment, cure infections, and reduce reinfection by hepatitis C,” according to the press release.

The upfront investment in hepatitis C management is projected to not only save lives, but also to save community health care costs in the long-term, according to the press release.

“This is a vigorous pilot program that provides the first steps toward the large goal of eliminating hepatitis C in the United States population,” said William Schaffner, MD, professor of infectious diseases at Vanderbilt University Medical Center, Nashville, Tennessee, in an interview.

Hepatitis C affects more than two million individuals in the US, and is often complicated by social and medical issues such as homelessness, substance abuse, and mental health issues, said Schaffner. Fortunately, hepatitis C can be treated with oral medications that cure the chronic viral infection, thereby ending ongoing liver injury and interrupting person-to-person transmission of the virus by sharing needles, he said.

Given that the population most affected with hepatitis C also is often homeless, with possible mental health issues and sharing of needles for illicit drug use, challenges in reaching this population include assuring them that the care they receive though this and other programs is nonjudgemental and helpful, Schaffner told GI & Hepatology News.

The oral medications that now can cure the chronic hepatitis C viral infections must be taken over a period of weeks, and patients who lead socially disorganized lives often need assistance to assure that the medicine is taken as intended, so trained and sensitive personnel who are committed to helping this population are needed to make treatment programs succeed, he said.

Looking ahead, “the purpose of the pilot studies that will be funded by this program is to explore various approaches to determine which are more successful in bringing patients in to be evaluated and then to complete treatment,” Schaffner added.

State and community-based organizations are among the entities eligible to apply for the program. Potential applicants can find information about the program and application materials on the SAMSHA website.

Schaffner had no financial conflicts to disclose.

A version of this article appeared on Medscape.com . 

A new $100 million pilot program launched by the Department of Health and Human Services (HHS) offers state and community-based health care organizations the resources for prevention, testing, and treatment of hepatitis C among individuals with substance use disorder and serious mental illness, according to an HHS press release.

The program, known as the Hepatitis C Elimination Initiative Pilot, will be administered by the Substance and Mental Health Administration. “This program is designed to support communities severely affected by homelessness and to gain insights on effective ways to identify patients, complete treatment, cure infections, and reduce reinfection by hepatitis C,” according to the press release.

The upfront investment in hepatitis C management is projected to not only save lives, but also to save community health care costs in the long-term, according to the press release.

“This is a vigorous pilot program that provides the first steps toward the large goal of eliminating hepatitis C in the United States population,” said William Schaffner, MD, professor of infectious diseases at Vanderbilt University Medical Center, Nashville, Tennessee, in an interview.

Hepatitis C affects more than two million individuals in the US, and is often complicated by social and medical issues such as homelessness, substance abuse, and mental health issues, said Schaffner. Fortunately, hepatitis C can be treated with oral medications that cure the chronic viral infection, thereby ending ongoing liver injury and interrupting person-to-person transmission of the virus by sharing needles, he said.

Given that the population most affected with hepatitis C also is often homeless, with possible mental health issues and sharing of needles for illicit drug use, challenges in reaching this population include assuring them that the care they receive though this and other programs is nonjudgemental and helpful, Schaffner told GI & Hepatology News.

The oral medications that now can cure the chronic hepatitis C viral infections must be taken over a period of weeks, and patients who lead socially disorganized lives often need assistance to assure that the medicine is taken as intended, so trained and sensitive personnel who are committed to helping this population are needed to make treatment programs succeed, he said.

Looking ahead, “the purpose of the pilot studies that will be funded by this program is to explore various approaches to determine which are more successful in bringing patients in to be evaluated and then to complete treatment,” Schaffner added.

State and community-based organizations are among the entities eligible to apply for the program. Potential applicants can find information about the program and application materials on the SAMSHA website.

Schaffner had no financial conflicts to disclose.

A version of this article appeared on Medscape.com . 

Genetic sequencing of peptides in rebound virus in individuals with HIV who had analytic treatment interruptions (ATIs) confirmed the peptides’ expression in HIV-1 infection, according to data presented at the International AIDS Society Conference on HIV Science. 

Previous research has shown that HIV-specific CD8 T-cell responses directed against five genetically conserved HIV-1 protein regions (Gag, Pol, Vif, Vpr, and Env) are associated with viral control, Josefina Marín-Rojas, PhD, Faculty of Medicine and Health, University of Sydney, and colleagues wrote in their abstract.

However, data on whether these peptides are expressed in rebound virus among individuals with HIV who experienced ATI are limited, they wrote.

The researchers applied an immunoinformatics analysis pipeline (IMAP) to select 182 peptides (IMAP-peptides) from structurally important and mutation-intolerant regions of HIV-1 proteins, senior author Sarah Palmer, PhD, co-director of the Centre for Virus Research at the Westmead Institute for Medical Research and professor in the Faculty of Medicine and Health at the University of Sydney, said in an interview.

“Our studies indicate if the immune system targets these structurally important and mutation-intolerant regions of HIV-1 proteins, this can contribute to virological control in the absence of HIV-1 therapy,” she explained.

The researchers reviewed data from the PULSE clinical trial, which included 68 men who have sex with men living with HIV in Australia. The men underwent three consecutive ATIs. A total of seven participants’ transiently controlled HIV rebound during the third ATI. The researchers examined whether the IMAP peptides were present in the HIV-1 RNA sequences of the rebound virus in four noncontrollers (patients who had viral rebound in all three ATIs) and five of the seven transient controllers who showed viral control during the third ATI.

The technique of near full-length HIV-1 RNA sequencing of rebound virus from three noncontrollers and two transient controllers identified the Gag, Pol, Vif, Vpr, and Env IMAP-peptides in 52%-100% of the viral sequences obtained from these participants across three ATI timepoints.

“We assumed that cells from people living with HIV that experience virological control after treatment interruption would have the immune response to our IMAP-peptides that we observed; however, we are amazed and encouraged by the level and extent of this immune response,” Palmer told this news organization.

The researchers also compared CD8 T-cell response between the IMAP peptides and a control peptide pool without the IMAP peptides.

The CD8 T-cells from three transient controllers had a 15- to 53-fold higher effector response to the IMAP-peptides than the CD8 T-cells from two noncontrollers, the researchers wrote in their abstract. The relative response to the IMAP-peptides in noncontrollers was 20 times lower than that to the control peptides, but the IMAP-peptide response in the transient controllers group was similar to that in the control group, the authors noted.

The results highlight the potential of IMAP in developing treatment strategies. Although the results are too preliminary to impact clinical practice at this time, the findings from the current study could lead to the development of an mRNA vaccine to clear HIV-infected cells from people living with HIV, Palmer told this news organization.

“Our next steps include developing and testing mRNA vaccine constructs that contain our IMAP-peptides to assess the immune response of cells from people living with HIV to these vaccines,” Palmer said. “From there we will conduct studies of the most promising mRNA vaccine constructs in a humanized mouse model,” she said.

 

Data Enhance Understanding of Immunity

The current study may provide information that can significantly impact understanding of the immune responses to HIV, David J. Cennimo, MD, associate professor of medicine and pediatrics in the Division of Infectious Disease at Rutgers New Jersey Medical School, Newark, New Jersey, said in an interview.

“The investigators looked at highly conserved regions of multiple HIV proteins,” said Cennimo, who was not involved in the study. “Conserved regions and antibody responses to them may play a role in controlling HIV viral replication and rebound,” Cennimo told this news organization. “The investigators showed these regions were present in rebounding viremia, and individuals that exhibited greater immune recognition of these regions suppressed rebound viremia longer, and perhaps targeting these regions could impact HIV prevention or cure strategies,” he said.

Secondarily, the study showed the success of the novel technique (IMAP) to identify conserved peptides, said Cennimo. The technique could potentially be applied to other viruses that mutate to escape host response, he said.The study was funded by the U.S. National Institutes of Health, the Foundation for AIDS Research, the Australian National Health and Medical Research Council, and Sandra and David Ansley. The researchers and Cennimo disclosed no financial conflicts of interest.

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

Genetic sequencing of peptides in rebound virus in individuals with HIV who had analytic treatment interruptions (ATIs) confirmed the peptides’ expression in HIV-1 infection, according to data presented at the International AIDS Society Conference on HIV Science. 

Previous research has shown that HIV-specific CD8 T-cell responses directed against five genetically conserved HIV-1 protein regions (Gag, Pol, Vif, Vpr, and Env) are associated with viral control, Josefina Marín-Rojas, PhD, Faculty of Medicine and Health, University of Sydney, and colleagues wrote in their abstract.

However, data on whether these peptides are expressed in rebound virus among individuals with HIV who experienced ATI are limited, they wrote.

The researchers applied an immunoinformatics analysis pipeline (IMAP) to select 182 peptides (IMAP-peptides) from structurally important and mutation-intolerant regions of HIV-1 proteins, senior author Sarah Palmer, PhD, co-director of the Centre for Virus Research at the Westmead Institute for Medical Research and professor in the Faculty of Medicine and Health at the University of Sydney, said in an interview.

“Our studies indicate if the immune system targets these structurally important and mutation-intolerant regions of HIV-1 proteins, this can contribute to virological control in the absence of HIV-1 therapy,” she explained.

The researchers reviewed data from the PULSE clinical trial, which included 68 men who have sex with men living with HIV in Australia. The men underwent three consecutive ATIs. A total of seven participants’ transiently controlled HIV rebound during the third ATI. The researchers examined whether the IMAP peptides were present in the HIV-1 RNA sequences of the rebound virus in four noncontrollers (patients who had viral rebound in all three ATIs) and five of the seven transient controllers who showed viral control during the third ATI.

The technique of near full-length HIV-1 RNA sequencing of rebound virus from three noncontrollers and two transient controllers identified the Gag, Pol, Vif, Vpr, and Env IMAP-peptides in 52%-100% of the viral sequences obtained from these participants across three ATI timepoints.

“We assumed that cells from people living with HIV that experience virological control after treatment interruption would have the immune response to our IMAP-peptides that we observed; however, we are amazed and encouraged by the level and extent of this immune response,” Palmer told this news organization.

The researchers also compared CD8 T-cell response between the IMAP peptides and a control peptide pool without the IMAP peptides.

The CD8 T-cells from three transient controllers had a 15- to 53-fold higher effector response to the IMAP-peptides than the CD8 T-cells from two noncontrollers, the researchers wrote in their abstract. The relative response to the IMAP-peptides in noncontrollers was 20 times lower than that to the control peptides, but the IMAP-peptide response in the transient controllers group was similar to that in the control group, the authors noted.

The results highlight the potential of IMAP in developing treatment strategies. Although the results are too preliminary to impact clinical practice at this time, the findings from the current study could lead to the development of an mRNA vaccine to clear HIV-infected cells from people living with HIV, Palmer told this news organization.

“Our next steps include developing and testing mRNA vaccine constructs that contain our IMAP-peptides to assess the immune response of cells from people living with HIV to these vaccines,” Palmer said. “From there we will conduct studies of the most promising mRNA vaccine constructs in a humanized mouse model,” she said.

 

Data Enhance Understanding of Immunity

The current study may provide information that can significantly impact understanding of the immune responses to HIV, David J. Cennimo, MD, associate professor of medicine and pediatrics in the Division of Infectious Disease at Rutgers New Jersey Medical School, Newark, New Jersey, said in an interview.

“The investigators looked at highly conserved regions of multiple HIV proteins,” said Cennimo, who was not involved in the study. “Conserved regions and antibody responses to them may play a role in controlling HIV viral replication and rebound,” Cennimo told this news organization. “The investigators showed these regions were present in rebounding viremia, and individuals that exhibited greater immune recognition of these regions suppressed rebound viremia longer, and perhaps targeting these regions could impact HIV prevention or cure strategies,” he said.

Secondarily, the study showed the success of the novel technique (IMAP) to identify conserved peptides, said Cennimo. The technique could potentially be applied to other viruses that mutate to escape host response, he said.The study was funded by the U.S. National Institutes of Health, the Foundation for AIDS Research, the Australian National Health and Medical Research Council, and Sandra and David Ansley. The researchers and Cennimo disclosed no financial conflicts of interest.

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

Genetic sequencing of peptides in rebound virus in individuals with HIV who had analytic treatment interruptions (ATIs) confirmed the peptides’ expression in HIV-1 infection, according to data presented at the International AIDS Society Conference on HIV Science. 

Previous research has shown that HIV-specific CD8 T-cell responses directed against five genetically conserved HIV-1 protein regions (Gag, Pol, Vif, Vpr, and Env) are associated with viral control, Josefina Marín-Rojas, PhD, Faculty of Medicine and Health, University of Sydney, and colleagues wrote in their abstract.

However, data on whether these peptides are expressed in rebound virus among individuals with HIV who experienced ATI are limited, they wrote.

The researchers applied an immunoinformatics analysis pipeline (IMAP) to select 182 peptides (IMAP-peptides) from structurally important and mutation-intolerant regions of HIV-1 proteins, senior author Sarah Palmer, PhD, co-director of the Centre for Virus Research at the Westmead Institute for Medical Research and professor in the Faculty of Medicine and Health at the University of Sydney, said in an interview.

“Our studies indicate if the immune system targets these structurally important and mutation-intolerant regions of HIV-1 proteins, this can contribute to virological control in the absence of HIV-1 therapy,” she explained.

The researchers reviewed data from the PULSE clinical trial, which included 68 men who have sex with men living with HIV in Australia. The men underwent three consecutive ATIs. A total of seven participants’ transiently controlled HIV rebound during the third ATI. The researchers examined whether the IMAP peptides were present in the HIV-1 RNA sequences of the rebound virus in four noncontrollers (patients who had viral rebound in all three ATIs) and five of the seven transient controllers who showed viral control during the third ATI.

The technique of near full-length HIV-1 RNA sequencing of rebound virus from three noncontrollers and two transient controllers identified the Gag, Pol, Vif, Vpr, and Env IMAP-peptides in 52%-100% of the viral sequences obtained from these participants across three ATI timepoints.

“We assumed that cells from people living with HIV that experience virological control after treatment interruption would have the immune response to our IMAP-peptides that we observed; however, we are amazed and encouraged by the level and extent of this immune response,” Palmer told this news organization.

The researchers also compared CD8 T-cell response between the IMAP peptides and a control peptide pool without the IMAP peptides.

The CD8 T-cells from three transient controllers had a 15- to 53-fold higher effector response to the IMAP-peptides than the CD8 T-cells from two noncontrollers, the researchers wrote in their abstract. The relative response to the IMAP-peptides in noncontrollers was 20 times lower than that to the control peptides, but the IMAP-peptide response in the transient controllers group was similar to that in the control group, the authors noted.

The results highlight the potential of IMAP in developing treatment strategies. Although the results are too preliminary to impact clinical practice at this time, the findings from the current study could lead to the development of an mRNA vaccine to clear HIV-infected cells from people living with HIV, Palmer told this news organization.

“Our next steps include developing and testing mRNA vaccine constructs that contain our IMAP-peptides to assess the immune response of cells from people living with HIV to these vaccines,” Palmer said. “From there we will conduct studies of the most promising mRNA vaccine constructs in a humanized mouse model,” she said.

 

Data Enhance Understanding of Immunity

The current study may provide information that can significantly impact understanding of the immune responses to HIV, David J. Cennimo, MD, associate professor of medicine and pediatrics in the Division of Infectious Disease at Rutgers New Jersey Medical School, Newark, New Jersey, said in an interview.

“The investigators looked at highly conserved regions of multiple HIV proteins,” said Cennimo, who was not involved in the study. “Conserved regions and antibody responses to them may play a role in controlling HIV viral replication and rebound,” Cennimo told this news organization. “The investigators showed these regions were present in rebounding viremia, and individuals that exhibited greater immune recognition of these regions suppressed rebound viremia longer, and perhaps targeting these regions could impact HIV prevention or cure strategies,” he said.

Secondarily, the study showed the success of the novel technique (IMAP) to identify conserved peptides, said Cennimo. The technique could potentially be applied to other viruses that mutate to escape host response, he said.The study was funded by the U.S. National Institutes of Health, the Foundation for AIDS Research, the Australian National Health and Medical Research Council, and Sandra and David Ansley. The researchers and Cennimo disclosed no financial conflicts of interest.

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