User login
Avatrombopag cut procedure-related transfusions in patients with thrombocytopenia, chronic liver disease
Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).
These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.
The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 109 per liter, and 40 mg if their baseline platelet count was 40-50 x 109 per liter. Procedures were scheduled for 10-13 days after treatment initiation.
“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 109 platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).
Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 109 per liter, and they all remained asymptomatic, the investigators said.
Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.
SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.
Thrombocytopenia in cirrhosis is frequent and multifactorial and includes sequestration in the spleen, reduced liver-derived thrombopoietin, bone marrow toxicity, and autoimmunity towards platelets. Severe thrombocytopenia (less than 50/nL) is rare in cirrhotic patients, but when it occurs may prevent required procedures from being performed or require platelet transfusions, which are associated with significant risks.
Previous attempts to increase platelets in cirrhotic patients with thrombopoietin agonists were halted because of increased frequency of portal vein thrombosis and hepatic decompensation.
Now avatrombopag has been specifically licensed with a 5-day regimen to increase platelets prior to elective interventions in severely thrombocytopenic (less than 50/nL) patients with chronic liver disease with a seemingly better safety profile than earlier treatments and good efficacy. The patient groups studied in the licensing trial had slightly milder but not significantly different liver disease, compared with those in the eltrombopag studies. The key difference was a pretreatment requirement of a portal vein flow of more than 10 cm/sec prior to enrollment, which likely reduced the risk of portal vein thrombosis. It is important that providers ready to use avatrombopag are aware of this.
Importantly, no data are currently available for patients with a Model for End-Stage Liver Disease score greater than 24, and very limited data are available for patients with Child B and Child C cirrhosis.
Given this limitation, careful judgment will be needed; a pretreatment portal vein flow may be advisable, though not a label requirement.
An observational study, NCT03554759, in patients with chronic liver disease and thrombocytopenia is ongoing and will further confirm the likely safety of avatrombopag.
Hans L. Tillmann, MD, is a clinical associate professor, East Carolina University, Greenville, and staff physician, Greenville (N.C.) VA Health Care Center. He has no relevant conflicts of interest.
Thrombocytopenia in cirrhosis is frequent and multifactorial and includes sequestration in the spleen, reduced liver-derived thrombopoietin, bone marrow toxicity, and autoimmunity towards platelets. Severe thrombocytopenia (less than 50/nL) is rare in cirrhotic patients, but when it occurs may prevent required procedures from being performed or require platelet transfusions, which are associated with significant risks.
Previous attempts to increase platelets in cirrhotic patients with thrombopoietin agonists were halted because of increased frequency of portal vein thrombosis and hepatic decompensation.
Now avatrombopag has been specifically licensed with a 5-day regimen to increase platelets prior to elective interventions in severely thrombocytopenic (less than 50/nL) patients with chronic liver disease with a seemingly better safety profile than earlier treatments and good efficacy. The patient groups studied in the licensing trial had slightly milder but not significantly different liver disease, compared with those in the eltrombopag studies. The key difference was a pretreatment requirement of a portal vein flow of more than 10 cm/sec prior to enrollment, which likely reduced the risk of portal vein thrombosis. It is important that providers ready to use avatrombopag are aware of this.
Importantly, no data are currently available for patients with a Model for End-Stage Liver Disease score greater than 24, and very limited data are available for patients with Child B and Child C cirrhosis.
Given this limitation, careful judgment will be needed; a pretreatment portal vein flow may be advisable, though not a label requirement.
An observational study, NCT03554759, in patients with chronic liver disease and thrombocytopenia is ongoing and will further confirm the likely safety of avatrombopag.
Hans L. Tillmann, MD, is a clinical associate professor, East Carolina University, Greenville, and staff physician, Greenville (N.C.) VA Health Care Center. He has no relevant conflicts of interest.
Thrombocytopenia in cirrhosis is frequent and multifactorial and includes sequestration in the spleen, reduced liver-derived thrombopoietin, bone marrow toxicity, and autoimmunity towards platelets. Severe thrombocytopenia (less than 50/nL) is rare in cirrhotic patients, but when it occurs may prevent required procedures from being performed or require platelet transfusions, which are associated with significant risks.
Previous attempts to increase platelets in cirrhotic patients with thrombopoietin agonists were halted because of increased frequency of portal vein thrombosis and hepatic decompensation.
Now avatrombopag has been specifically licensed with a 5-day regimen to increase platelets prior to elective interventions in severely thrombocytopenic (less than 50/nL) patients with chronic liver disease with a seemingly better safety profile than earlier treatments and good efficacy. The patient groups studied in the licensing trial had slightly milder but not significantly different liver disease, compared with those in the eltrombopag studies. The key difference was a pretreatment requirement of a portal vein flow of more than 10 cm/sec prior to enrollment, which likely reduced the risk of portal vein thrombosis. It is important that providers ready to use avatrombopag are aware of this.
Importantly, no data are currently available for patients with a Model for End-Stage Liver Disease score greater than 24, and very limited data are available for patients with Child B and Child C cirrhosis.
Given this limitation, careful judgment will be needed; a pretreatment portal vein flow may be advisable, though not a label requirement.
An observational study, NCT03554759, in patients with chronic liver disease and thrombocytopenia is ongoing and will further confirm the likely safety of avatrombopag.
Hans L. Tillmann, MD, is a clinical associate professor, East Carolina University, Greenville, and staff physician, Greenville (N.C.) VA Health Care Center. He has no relevant conflicts of interest.
Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).
These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.
The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 109 per liter, and 40 mg if their baseline platelet count was 40-50 x 109 per liter. Procedures were scheduled for 10-13 days after treatment initiation.
“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 109 platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).
Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 109 per liter, and they all remained asymptomatic, the investigators said.
Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.
SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.
Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.
SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION
In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).
These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.
The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 109 per liter, and 40 mg if their baseline platelet count was 40-50 x 109 per liter. Procedures were scheduled for 10-13 days after treatment initiation.
“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 109 platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).
Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 109 per liter, and they all remained asymptomatic, the investigators said.
Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.
SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.
FROM GASTROENTEROLOGY
Key clinical point: Once-daily treatment with oral avatrombopag significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures.
Major finding: In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).
Study details: ADAPT-1 and ADAPT-2, international, randomized, double-blind, placebo-controlled, phase III trials.
Disclosures: Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, BMS, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.
Source: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.
AGA Clinical Practice Update: Tumor seeding with endoscopic procedures
Certain endoscopic procedures carry the risk of tumor seeding. In prior studies, these rates were 0.005% to 0.009% for patients undergoing percutaneous abdominal biopsy, 1.6% for percutaneous radiofrequency ablation of hepatocellular carcinoma, and 2.7% for needle biopsy of hepatocellular carcinoma. When placing percutaneous endoscopic gastrostomy tubes, the “pull-through” technique is most common but “should be avoided in all patients with oropharyngeal or esophageal cancer,” the clinical practice update states. The authors cite multiple studies linking the pull-through technique to metastasis.
Clinicians also should avoid fine needle aspiration (FNA) of primary hilar cholangiocarcinomas, especially in patients who are surgical or transplant candidates, wrote Ferga C. Gleeson, MB, BCh, and her associates, MD Anderson Cancer Center, Houston. The report is in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2018.05.014).
For patients with suspected pancreatic cancer, the clinical practice update recommends endoscopic ultrasound (EUS)–guided FNA “in any site within the gland when a confirmatory diagnosis of cancer would alter patient management.” The authors also emphasize promptly closing iatrogenic perforations during endoscopic mucosal resection and endoscopic submucosal dissection and practicing nonexposure techniques during endoscopic resection of subepithelial lesions.
For patients with cholangiocarcinoma, primary tumor FNA is controversial because it can be the sole means of cancer diagnosis but also significantly increases the risk of peritoneal metastasis, especially in the setting of larger tumor size, thicker needles, multiple passes, high-grade tumors, and scanty normal tissue along the needle tract, the experts note. Because FNA “may render a patient with cholangiocarcinoma ineligible for entry into a liver transplantation protocol,” it is “best to avoid” or at least discuss with a transplant hepatologist, they add.
However, EUS is appropriate when evaluating suspicious lymphadenopathy in liver transplantation candidates with cholangiocarcinoma, they note. This is because imaging techniques have inadequate sensitivity and a positive EUS result would preclude unnecessary neoadjuvant chemoradiation and staging laparotomy. If FNA is negative, patients do require staging laparotomy to verify the absence of nodal disease before transplantation, according to the clinical practice update.
Endoscopic mucosal and submucosal resection are valuable treatment options for esophageal, gastric, and colonic dysplasia and early carcinoma, but they also can lead to unintended gastrointestinal perforation. In past studies, rates of iatrogenic perforation were 1% when patients underwent endoscopic mucosal resection and 5% when they underwent submucosal resection. For patients with any stage of gastric cancer, an accidental perforation can seed the peritoneum with cancer cells from the contents of the stomach. Contact with a primary tumor also can cause shedding of tumor cells that can enter the peritoneal cavity through a perforation. Although most of these cases do not have clinically significant outcomes, perforations need to be promptly closed and should be avoided, if at all possible, during endoscopic full-thickness resections, the experts wrote.
They recommend using nonexposure techniques while resecting subepithelial tumors and call for more safety studies of endoscopic submucosal dissection of malignancies and endoscopic full-thickness resection of subepithelial lesions. “These studies should focus on individual reports or case series of peritoneal or mediastinal examination during surgery following failed resection of these lesions,” the authors concluded.
Dr. Gleeson and her associates disclosed no funding sources and reported having no conflicts of interest.
SOURCE: Gleeson FC et al. Clin Gastroenterol Hepatol. 2018 May 17. doi: 10.1016/j.cgh.2018.05.014.
Certain endoscopic procedures carry the risk of tumor seeding. In prior studies, these rates were 0.005% to 0.009% for patients undergoing percutaneous abdominal biopsy, 1.6% for percutaneous radiofrequency ablation of hepatocellular carcinoma, and 2.7% for needle biopsy of hepatocellular carcinoma. When placing percutaneous endoscopic gastrostomy tubes, the “pull-through” technique is most common but “should be avoided in all patients with oropharyngeal or esophageal cancer,” the clinical practice update states. The authors cite multiple studies linking the pull-through technique to metastasis.
Clinicians also should avoid fine needle aspiration (FNA) of primary hilar cholangiocarcinomas, especially in patients who are surgical or transplant candidates, wrote Ferga C. Gleeson, MB, BCh, and her associates, MD Anderson Cancer Center, Houston. The report is in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2018.05.014).
For patients with suspected pancreatic cancer, the clinical practice update recommends endoscopic ultrasound (EUS)–guided FNA “in any site within the gland when a confirmatory diagnosis of cancer would alter patient management.” The authors also emphasize promptly closing iatrogenic perforations during endoscopic mucosal resection and endoscopic submucosal dissection and practicing nonexposure techniques during endoscopic resection of subepithelial lesions.
For patients with cholangiocarcinoma, primary tumor FNA is controversial because it can be the sole means of cancer diagnosis but also significantly increases the risk of peritoneal metastasis, especially in the setting of larger tumor size, thicker needles, multiple passes, high-grade tumors, and scanty normal tissue along the needle tract, the experts note. Because FNA “may render a patient with cholangiocarcinoma ineligible for entry into a liver transplantation protocol,” it is “best to avoid” or at least discuss with a transplant hepatologist, they add.
However, EUS is appropriate when evaluating suspicious lymphadenopathy in liver transplantation candidates with cholangiocarcinoma, they note. This is because imaging techniques have inadequate sensitivity and a positive EUS result would preclude unnecessary neoadjuvant chemoradiation and staging laparotomy. If FNA is negative, patients do require staging laparotomy to verify the absence of nodal disease before transplantation, according to the clinical practice update.
Endoscopic mucosal and submucosal resection are valuable treatment options for esophageal, gastric, and colonic dysplasia and early carcinoma, but they also can lead to unintended gastrointestinal perforation. In past studies, rates of iatrogenic perforation were 1% when patients underwent endoscopic mucosal resection and 5% when they underwent submucosal resection. For patients with any stage of gastric cancer, an accidental perforation can seed the peritoneum with cancer cells from the contents of the stomach. Contact with a primary tumor also can cause shedding of tumor cells that can enter the peritoneal cavity through a perforation. Although most of these cases do not have clinically significant outcomes, perforations need to be promptly closed and should be avoided, if at all possible, during endoscopic full-thickness resections, the experts wrote.
They recommend using nonexposure techniques while resecting subepithelial tumors and call for more safety studies of endoscopic submucosal dissection of malignancies and endoscopic full-thickness resection of subepithelial lesions. “These studies should focus on individual reports or case series of peritoneal or mediastinal examination during surgery following failed resection of these lesions,” the authors concluded.
Dr. Gleeson and her associates disclosed no funding sources and reported having no conflicts of interest.
SOURCE: Gleeson FC et al. Clin Gastroenterol Hepatol. 2018 May 17. doi: 10.1016/j.cgh.2018.05.014.
Certain endoscopic procedures carry the risk of tumor seeding. In prior studies, these rates were 0.005% to 0.009% for patients undergoing percutaneous abdominal biopsy, 1.6% for percutaneous radiofrequency ablation of hepatocellular carcinoma, and 2.7% for needle biopsy of hepatocellular carcinoma. When placing percutaneous endoscopic gastrostomy tubes, the “pull-through” technique is most common but “should be avoided in all patients with oropharyngeal or esophageal cancer,” the clinical practice update states. The authors cite multiple studies linking the pull-through technique to metastasis.
Clinicians also should avoid fine needle aspiration (FNA) of primary hilar cholangiocarcinomas, especially in patients who are surgical or transplant candidates, wrote Ferga C. Gleeson, MB, BCh, and her associates, MD Anderson Cancer Center, Houston. The report is in the September issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2018.05.014).
For patients with suspected pancreatic cancer, the clinical practice update recommends endoscopic ultrasound (EUS)–guided FNA “in any site within the gland when a confirmatory diagnosis of cancer would alter patient management.” The authors also emphasize promptly closing iatrogenic perforations during endoscopic mucosal resection and endoscopic submucosal dissection and practicing nonexposure techniques during endoscopic resection of subepithelial lesions.
For patients with cholangiocarcinoma, primary tumor FNA is controversial because it can be the sole means of cancer diagnosis but also significantly increases the risk of peritoneal metastasis, especially in the setting of larger tumor size, thicker needles, multiple passes, high-grade tumors, and scanty normal tissue along the needle tract, the experts note. Because FNA “may render a patient with cholangiocarcinoma ineligible for entry into a liver transplantation protocol,” it is “best to avoid” or at least discuss with a transplant hepatologist, they add.
However, EUS is appropriate when evaluating suspicious lymphadenopathy in liver transplantation candidates with cholangiocarcinoma, they note. This is because imaging techniques have inadequate sensitivity and a positive EUS result would preclude unnecessary neoadjuvant chemoradiation and staging laparotomy. If FNA is negative, patients do require staging laparotomy to verify the absence of nodal disease before transplantation, according to the clinical practice update.
Endoscopic mucosal and submucosal resection are valuable treatment options for esophageal, gastric, and colonic dysplasia and early carcinoma, but they also can lead to unintended gastrointestinal perforation. In past studies, rates of iatrogenic perforation were 1% when patients underwent endoscopic mucosal resection and 5% when they underwent submucosal resection. For patients with any stage of gastric cancer, an accidental perforation can seed the peritoneum with cancer cells from the contents of the stomach. Contact with a primary tumor also can cause shedding of tumor cells that can enter the peritoneal cavity through a perforation. Although most of these cases do not have clinically significant outcomes, perforations need to be promptly closed and should be avoided, if at all possible, during endoscopic full-thickness resections, the experts wrote.
They recommend using nonexposure techniques while resecting subepithelial tumors and call for more safety studies of endoscopic submucosal dissection of malignancies and endoscopic full-thickness resection of subepithelial lesions. “These studies should focus on individual reports or case series of peritoneal or mediastinal examination during surgery following failed resection of these lesions,” the authors concluded.
Dr. Gleeson and her associates disclosed no funding sources and reported having no conflicts of interest.
SOURCE: Gleeson FC et al. Clin Gastroenterol Hepatol. 2018 May 17. doi: 10.1016/j.cgh.2018.05.014.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Endoscopic screening tied to significantly lower risk of death from gastric cancer
Endoscopic screening was associated with an approximately 40% reduction in risk of death from gastric cancer in a systematic review and meta-analysis of studies from Asian countries.
The study is the first systematic review and meta-analysis of gastric cancer mortality and incidence after endoscopic screening, wrote Xing Zhang, MD, of the China Academy of Chinese Medical Sciences in Beijing with his associates. “Population-based prospective cohort studies are warranted to confirm our findings,” the reviewers wrote in the August issue of Gastroenterology.
In general, the rates of gastric cancer and related mortality in East Asian countries are significantly higher than global averages. As a result, countries in this region have implemented a variety of national and opportunistic screening programs that vary from country to country. Japan, for example, has a national screening program based on photofluorography. “Although data are inconsistent, most studies have shown a 40%-60% decrease in the mortality of gastric cancer in those who have been screened using photofluorography,” the reviewers noted. When findings are positive, follow-up endoscopy is recommended. However, debates persist about whether population-level endoscopy significantly improves hard endpoints in gastric cancer, such as incidence and mortality.
To help clarify the population-level benefits of endoscopic screening, Dr. Zhang and his associates searched PubMed and EMBASE; they identified six cohort studies and four nested case-control studies that included approximately 342,000 adults from Asia who did not have baseline gastric cancer but did undergo surveillance endoscopy at least once. Studies of both mass and opportunistic screening were included. Each study included a comparator; reported incidence, mortality, or both; and was published by March 8, 2018.
Endoscopic screening was tied to a 40% reduction in the relative risk of death from gastric cancer (risk ratio, 0.60; 95% confidence interval, 0.49-0.73). There also was a slight trend toward increased incidence of gastric cancer, which was not statistically significant (RR, 1.14; 95% CI, 0.93-1.40). However, only two studies examined the incidence of gastric cancer, so this outcome “should be interpreted with caution,” the reviewers wrote. Endoscopic screening also was associated with a significantly lower risk of death from gastric cancer, compared with radiographic screening (RR, 0.33; 95% CI, 0.12-0.91).
Endoscopic screening did not significantly reduce mortality, compared with expected deaths (RR, 0.67; 95% CI, 0.38-1.16), the reviewers reported. This might be because the reviewers included an outlier study conducted in Linqu County, China, which has some of the highest rates of gastric cancer death in the world, they noted. Endoscopic surveillance did not reduce mortality in the Linqu County study, but screenings were spaced by 4.5 years, which was probably too long to show an effect, especially in a high-risk region, they added. The study in Linqu County accounted for most of the heterogeneity among studies, and removing it from the pooled analysis produced a “slightly more pronounced reduction in gastric cancer mortality,” with an RR of 0.56, they noted.
Funders included the National Natural Science Foundation and the National Twelfth Five-Year Plan for Science and Technology Support Program of China. The reviewers reported having no relevant conflicts of interest.
SOURCE: Zhang X, et al. Gastroenterology. 2018 Apr 30. doi: 10.1053/j.gastro.2018.04.026.
Gastric cancer remains the third most common cause of cancer death worldwide, although incidence and mortality rates have been declining for several years. For populations in eastern Asia – a region that carries the unenviable tag of having the highest gastric cancer mortality rates in the world – finding ways to reduce the burden of this disease remains a key priority.
New findings reported by Zhang and his colleagues have highlighted a strong evidence base for one mode of gastric cancer control in eastern Asia. The systematic review team demonstrated a significant 40% reduction in the risk of death from gastric cancer when screening was conducted in general populations. The magnitude of this benefit likely reflects the appropriateness of screening in such high-incidence areas, although this finding might not necessarily be extrapolated to other regions.
The authors cautioned that screening did not reduce gastric cancer incidence, although only two studies were included. However, reduced incidence is often not an aim of screening programs; indeed, to detect more gastric cancers at an earlier stage can be an intentional outcome.
The observed benefits might be somewhat attributed to lead time bias (whereby individuals are diagnosed at a younger age than they would have presented symptomatically but still die at the same age) or length time bias (detecting only the slower-growing biological tumors). Further refinement of optimal screening intervals is also required. Nevertheless, public health policy makers in Japan and Korea, where national screening programs already exist, should be reassured by these review findings.
Helen Coleman, PhD, BSc(Hons), is a senior lecturer and lead of the Cancer Epidemiology Research Group at the Centre for Public Health and Centre for Cancer Research and Cell Biology at Queen’s University Belfast. She has no conflicts of interest.
Gastric cancer remains the third most common cause of cancer death worldwide, although incidence and mortality rates have been declining for several years. For populations in eastern Asia – a region that carries the unenviable tag of having the highest gastric cancer mortality rates in the world – finding ways to reduce the burden of this disease remains a key priority.
New findings reported by Zhang and his colleagues have highlighted a strong evidence base for one mode of gastric cancer control in eastern Asia. The systematic review team demonstrated a significant 40% reduction in the risk of death from gastric cancer when screening was conducted in general populations. The magnitude of this benefit likely reflects the appropriateness of screening in such high-incidence areas, although this finding might not necessarily be extrapolated to other regions.
The authors cautioned that screening did not reduce gastric cancer incidence, although only two studies were included. However, reduced incidence is often not an aim of screening programs; indeed, to detect more gastric cancers at an earlier stage can be an intentional outcome.
The observed benefits might be somewhat attributed to lead time bias (whereby individuals are diagnosed at a younger age than they would have presented symptomatically but still die at the same age) or length time bias (detecting only the slower-growing biological tumors). Further refinement of optimal screening intervals is also required. Nevertheless, public health policy makers in Japan and Korea, where national screening programs already exist, should be reassured by these review findings.
Helen Coleman, PhD, BSc(Hons), is a senior lecturer and lead of the Cancer Epidemiology Research Group at the Centre for Public Health and Centre for Cancer Research and Cell Biology at Queen’s University Belfast. She has no conflicts of interest.
Gastric cancer remains the third most common cause of cancer death worldwide, although incidence and mortality rates have been declining for several years. For populations in eastern Asia – a region that carries the unenviable tag of having the highest gastric cancer mortality rates in the world – finding ways to reduce the burden of this disease remains a key priority.
New findings reported by Zhang and his colleagues have highlighted a strong evidence base for one mode of gastric cancer control in eastern Asia. The systematic review team demonstrated a significant 40% reduction in the risk of death from gastric cancer when screening was conducted in general populations. The magnitude of this benefit likely reflects the appropriateness of screening in such high-incidence areas, although this finding might not necessarily be extrapolated to other regions.
The authors cautioned that screening did not reduce gastric cancer incidence, although only two studies were included. However, reduced incidence is often not an aim of screening programs; indeed, to detect more gastric cancers at an earlier stage can be an intentional outcome.
The observed benefits might be somewhat attributed to lead time bias (whereby individuals are diagnosed at a younger age than they would have presented symptomatically but still die at the same age) or length time bias (detecting only the slower-growing biological tumors). Further refinement of optimal screening intervals is also required. Nevertheless, public health policy makers in Japan and Korea, where national screening programs already exist, should be reassured by these review findings.
Helen Coleman, PhD, BSc(Hons), is a senior lecturer and lead of the Cancer Epidemiology Research Group at the Centre for Public Health and Centre for Cancer Research and Cell Biology at Queen’s University Belfast. She has no conflicts of interest.
Endoscopic screening was associated with an approximately 40% reduction in risk of death from gastric cancer in a systematic review and meta-analysis of studies from Asian countries.
The study is the first systematic review and meta-analysis of gastric cancer mortality and incidence after endoscopic screening, wrote Xing Zhang, MD, of the China Academy of Chinese Medical Sciences in Beijing with his associates. “Population-based prospective cohort studies are warranted to confirm our findings,” the reviewers wrote in the August issue of Gastroenterology.
In general, the rates of gastric cancer and related mortality in East Asian countries are significantly higher than global averages. As a result, countries in this region have implemented a variety of national and opportunistic screening programs that vary from country to country. Japan, for example, has a national screening program based on photofluorography. “Although data are inconsistent, most studies have shown a 40%-60% decrease in the mortality of gastric cancer in those who have been screened using photofluorography,” the reviewers noted. When findings are positive, follow-up endoscopy is recommended. However, debates persist about whether population-level endoscopy significantly improves hard endpoints in gastric cancer, such as incidence and mortality.
To help clarify the population-level benefits of endoscopic screening, Dr. Zhang and his associates searched PubMed and EMBASE; they identified six cohort studies and four nested case-control studies that included approximately 342,000 adults from Asia who did not have baseline gastric cancer but did undergo surveillance endoscopy at least once. Studies of both mass and opportunistic screening were included. Each study included a comparator; reported incidence, mortality, or both; and was published by March 8, 2018.
Endoscopic screening was tied to a 40% reduction in the relative risk of death from gastric cancer (risk ratio, 0.60; 95% confidence interval, 0.49-0.73). There also was a slight trend toward increased incidence of gastric cancer, which was not statistically significant (RR, 1.14; 95% CI, 0.93-1.40). However, only two studies examined the incidence of gastric cancer, so this outcome “should be interpreted with caution,” the reviewers wrote. Endoscopic screening also was associated with a significantly lower risk of death from gastric cancer, compared with radiographic screening (RR, 0.33; 95% CI, 0.12-0.91).
Endoscopic screening did not significantly reduce mortality, compared with expected deaths (RR, 0.67; 95% CI, 0.38-1.16), the reviewers reported. This might be because the reviewers included an outlier study conducted in Linqu County, China, which has some of the highest rates of gastric cancer death in the world, they noted. Endoscopic surveillance did not reduce mortality in the Linqu County study, but screenings were spaced by 4.5 years, which was probably too long to show an effect, especially in a high-risk region, they added. The study in Linqu County accounted for most of the heterogeneity among studies, and removing it from the pooled analysis produced a “slightly more pronounced reduction in gastric cancer mortality,” with an RR of 0.56, they noted.
Funders included the National Natural Science Foundation and the National Twelfth Five-Year Plan for Science and Technology Support Program of China. The reviewers reported having no relevant conflicts of interest.
SOURCE: Zhang X, et al. Gastroenterology. 2018 Apr 30. doi: 10.1053/j.gastro.2018.04.026.
Endoscopic screening was associated with an approximately 40% reduction in risk of death from gastric cancer in a systematic review and meta-analysis of studies from Asian countries.
The study is the first systematic review and meta-analysis of gastric cancer mortality and incidence after endoscopic screening, wrote Xing Zhang, MD, of the China Academy of Chinese Medical Sciences in Beijing with his associates. “Population-based prospective cohort studies are warranted to confirm our findings,” the reviewers wrote in the August issue of Gastroenterology.
In general, the rates of gastric cancer and related mortality in East Asian countries are significantly higher than global averages. As a result, countries in this region have implemented a variety of national and opportunistic screening programs that vary from country to country. Japan, for example, has a national screening program based on photofluorography. “Although data are inconsistent, most studies have shown a 40%-60% decrease in the mortality of gastric cancer in those who have been screened using photofluorography,” the reviewers noted. When findings are positive, follow-up endoscopy is recommended. However, debates persist about whether population-level endoscopy significantly improves hard endpoints in gastric cancer, such as incidence and mortality.
To help clarify the population-level benefits of endoscopic screening, Dr. Zhang and his associates searched PubMed and EMBASE; they identified six cohort studies and four nested case-control studies that included approximately 342,000 adults from Asia who did not have baseline gastric cancer but did undergo surveillance endoscopy at least once. Studies of both mass and opportunistic screening were included. Each study included a comparator; reported incidence, mortality, or both; and was published by March 8, 2018.
Endoscopic screening was tied to a 40% reduction in the relative risk of death from gastric cancer (risk ratio, 0.60; 95% confidence interval, 0.49-0.73). There also was a slight trend toward increased incidence of gastric cancer, which was not statistically significant (RR, 1.14; 95% CI, 0.93-1.40). However, only two studies examined the incidence of gastric cancer, so this outcome “should be interpreted with caution,” the reviewers wrote. Endoscopic screening also was associated with a significantly lower risk of death from gastric cancer, compared with radiographic screening (RR, 0.33; 95% CI, 0.12-0.91).
Endoscopic screening did not significantly reduce mortality, compared with expected deaths (RR, 0.67; 95% CI, 0.38-1.16), the reviewers reported. This might be because the reviewers included an outlier study conducted in Linqu County, China, which has some of the highest rates of gastric cancer death in the world, they noted. Endoscopic surveillance did not reduce mortality in the Linqu County study, but screenings were spaced by 4.5 years, which was probably too long to show an effect, especially in a high-risk region, they added. The study in Linqu County accounted for most of the heterogeneity among studies, and removing it from the pooled analysis produced a “slightly more pronounced reduction in gastric cancer mortality,” with an RR of 0.56, they noted.
Funders included the National Natural Science Foundation and the National Twelfth Five-Year Plan for Science and Technology Support Program of China. The reviewers reported having no relevant conflicts of interest.
SOURCE: Zhang X, et al. Gastroenterology. 2018 Apr 30. doi: 10.1053/j.gastro.2018.04.026.
FROM GASTROENTEROLOGY
Key clinical point: Endoscopic screening was associated with a significant decrease in risk of death from gastric cancer.
Major finding: Compared with no screening, the reduction in risk was 40% (risk ratio, 0.60; 95% confidence interval, 0.49-0.73).
Study details: Systematic review and meta-analysis of six cohort studies and four nested case-control studies of approximately 342,000 adults.
Disclosures: Funders included the National Natural Science Foundation and the National Twelfth Five-Year Plan for Science and Technology Support Program of China. The reviewers reported having no relevant conflicts of interest.
Source: Zhang X et al. Gastroenterology. 2018 Apr 30. doi: 10.1053/j.gastro.2018.04.026.
Fine-needle aspirate, biopsy found equivalent in randomized trial
For patients with pancreatic masses, infiltrated lymph nodes, or submucosal tumors, endoscopic ultrasound-guided fine-needle aspirate and fine-needle biopsy produced a comparable diagnostic yield with a similar number of needle passes, according to the results of a multicenter, randomized clinical trial.
Diagnostic yields were 91% for fine-needle aspirate versus 89% for fine-needle biopsy, with a median of one needle pass needed to obtain a diagnostic sample for each technique, reported Satish Nagula, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his associates. The findings were published in the August issue of Clinical Gastroenterology and Hepatology.
Previously, two small, single-center randomized trials yielded conflicting data on whether fine-needle biopsy produces better diagnostic yield than fine-needle aspirate, the investigators noted. The results of four other studies indicated that the two techniques performed similarly. However, “many of these trials had study designs that did not allow for realistic comparisons of needle performance,” they noted. For example, the studies only analyzed the results of the first needle pass or only included specimens with visible core tissue.
The current study included six tertiary care centers that perform high volumes of endoscopic ultrasound. In all, 135 patients were randomly assigned to undergo fine-needle aspirate or fine-needle biopsy. When rapid on-site cytologic evaluation was used, the clinicians made consecutive needle passes until they considered the specimen adequate. Most lesions (77%) were masses, but 17% were lymph nodes, and 7% were submucosal tumors, the researchers said. The endoscopists used a curvilinear array echoendoscope (GF-UC140P or GF-UCT140; Olympus America, Central Valley, Penn.). They performed fine-needle aspirate or biopsy by using either a 22-gauge or 25-gauge needle at their own discretion.
The final diagnosis was malignancy for 70% of lesions, reactive lymphadenopathy for 11% of lesions, and spindle cell tumors in 9% of cases, the investigators said. Diagnostic yield was similar whether or not rapid on-site cytologic evaluation was used. Fine-needle aspiration detected cancer with a sensitivity of 90% and a specificity of 100%. Fine-needle biopsy had a sensitivity of 89% and a specificity of 100%. Adverse events were uncommon (1%), but one patient was hospitalized with pancreatitis for 2 days after undergoing fine-needle biopsy of a pancreatic body lesion.
The researchers noted several study limitations. “Ideally, each patient would undergo both fine-needle aspirate and fine-needle biopsy, allowing each as their own internal control,” they wrote. “It was considered too expensive to use two different needles in this unfunded study.” There also was no central pathology review, which they called “fiscally not feasible.”
There were no funding sources, and the investigators reported having no relevant conflicts of interest.SOURCE: Nagula S et al. Clin Gastroenterol Hepatol. 2017 Jun 14. doi: 10.1016/j.cgh.2017.06.013.
For patients with pancreatic masses, infiltrated lymph nodes, or submucosal tumors, endoscopic ultrasound-guided fine-needle aspirate and fine-needle biopsy produced a comparable diagnostic yield with a similar number of needle passes, according to the results of a multicenter, randomized clinical trial.
Diagnostic yields were 91% for fine-needle aspirate versus 89% for fine-needle biopsy, with a median of one needle pass needed to obtain a diagnostic sample for each technique, reported Satish Nagula, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his associates. The findings were published in the August issue of Clinical Gastroenterology and Hepatology.
Previously, two small, single-center randomized trials yielded conflicting data on whether fine-needle biopsy produces better diagnostic yield than fine-needle aspirate, the investigators noted. The results of four other studies indicated that the two techniques performed similarly. However, “many of these trials had study designs that did not allow for realistic comparisons of needle performance,” they noted. For example, the studies only analyzed the results of the first needle pass or only included specimens with visible core tissue.
The current study included six tertiary care centers that perform high volumes of endoscopic ultrasound. In all, 135 patients were randomly assigned to undergo fine-needle aspirate or fine-needle biopsy. When rapid on-site cytologic evaluation was used, the clinicians made consecutive needle passes until they considered the specimen adequate. Most lesions (77%) were masses, but 17% were lymph nodes, and 7% were submucosal tumors, the researchers said. The endoscopists used a curvilinear array echoendoscope (GF-UC140P or GF-UCT140; Olympus America, Central Valley, Penn.). They performed fine-needle aspirate or biopsy by using either a 22-gauge or 25-gauge needle at their own discretion.
The final diagnosis was malignancy for 70% of lesions, reactive lymphadenopathy for 11% of lesions, and spindle cell tumors in 9% of cases, the investigators said. Diagnostic yield was similar whether or not rapid on-site cytologic evaluation was used. Fine-needle aspiration detected cancer with a sensitivity of 90% and a specificity of 100%. Fine-needle biopsy had a sensitivity of 89% and a specificity of 100%. Adverse events were uncommon (1%), but one patient was hospitalized with pancreatitis for 2 days after undergoing fine-needle biopsy of a pancreatic body lesion.
The researchers noted several study limitations. “Ideally, each patient would undergo both fine-needle aspirate and fine-needle biopsy, allowing each as their own internal control,” they wrote. “It was considered too expensive to use two different needles in this unfunded study.” There also was no central pathology review, which they called “fiscally not feasible.”
There were no funding sources, and the investigators reported having no relevant conflicts of interest.SOURCE: Nagula S et al. Clin Gastroenterol Hepatol. 2017 Jun 14. doi: 10.1016/j.cgh.2017.06.013.
For patients with pancreatic masses, infiltrated lymph nodes, or submucosal tumors, endoscopic ultrasound-guided fine-needle aspirate and fine-needle biopsy produced a comparable diagnostic yield with a similar number of needle passes, according to the results of a multicenter, randomized clinical trial.
Diagnostic yields were 91% for fine-needle aspirate versus 89% for fine-needle biopsy, with a median of one needle pass needed to obtain a diagnostic sample for each technique, reported Satish Nagula, MD, of the Icahn School of Medicine at Mount Sinai, New York, and his associates. The findings were published in the August issue of Clinical Gastroenterology and Hepatology.
Previously, two small, single-center randomized trials yielded conflicting data on whether fine-needle biopsy produces better diagnostic yield than fine-needle aspirate, the investigators noted. The results of four other studies indicated that the two techniques performed similarly. However, “many of these trials had study designs that did not allow for realistic comparisons of needle performance,” they noted. For example, the studies only analyzed the results of the first needle pass or only included specimens with visible core tissue.
The current study included six tertiary care centers that perform high volumes of endoscopic ultrasound. In all, 135 patients were randomly assigned to undergo fine-needle aspirate or fine-needle biopsy. When rapid on-site cytologic evaluation was used, the clinicians made consecutive needle passes until they considered the specimen adequate. Most lesions (77%) were masses, but 17% were lymph nodes, and 7% were submucosal tumors, the researchers said. The endoscopists used a curvilinear array echoendoscope (GF-UC140P or GF-UCT140; Olympus America, Central Valley, Penn.). They performed fine-needle aspirate or biopsy by using either a 22-gauge or 25-gauge needle at their own discretion.
The final diagnosis was malignancy for 70% of lesions, reactive lymphadenopathy for 11% of lesions, and spindle cell tumors in 9% of cases, the investigators said. Diagnostic yield was similar whether or not rapid on-site cytologic evaluation was used. Fine-needle aspiration detected cancer with a sensitivity of 90% and a specificity of 100%. Fine-needle biopsy had a sensitivity of 89% and a specificity of 100%. Adverse events were uncommon (1%), but one patient was hospitalized with pancreatitis for 2 days after undergoing fine-needle biopsy of a pancreatic body lesion.
The researchers noted several study limitations. “Ideally, each patient would undergo both fine-needle aspirate and fine-needle biopsy, allowing each as their own internal control,” they wrote. “It was considered too expensive to use two different needles in this unfunded study.” There also was no central pathology review, which they called “fiscally not feasible.”
There were no funding sources, and the investigators reported having no relevant conflicts of interest.SOURCE: Nagula S et al. Clin Gastroenterol Hepatol. 2017 Jun 14. doi: 10.1016/j.cgh.2017.06.013.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Endoscopic ultrasound-guided final-needle aspirate and fine-needle biopsy performed similarly in solid lesions.
Major finding: Diagnostic yields were 91% for fine-needle aspirate and 89% for fine-needle biopsy, with a median of one needle pass needed to obtain a diagnostic sample for each technique.
Study details: Multicenter randomized study of 135 patients.
Disclosures: The study was not funded, and the investigators reported having no relevant conflicts of interest.
Source: Nagula S et al. Clin Gastroenterol Hepatol. 2017 Jun 14. doi: 10.1016/j.cgh.2017.06.013.
Who are the 'high-need, high-cost' patients?
Among patients hospitalized with gastrointestinal and liver diseases, a clearly identifiable subset uses significantly more health care resources, which incurs significantly greater costs, according to the results of a national database analysis published in the August issue of Clinical Gastroenterology and Hepatology.
Compared with otherwise similar inpatients, these “high-need, high-cost” individuals are significantly more likely to be enrolled in Medicare or Medicaid, to have lower income, to initially be admitted to a large, rural hospital, to have multiple comorbidities, to be obese, or to be hospitalized for infection, said Nghia Nguyen, MD, and his associates. “[A] small fraction of high-need, high-cost patients contribute disproportionately to hospitalization costs,” they wrote. “Population health management directed toward these patients would facilitate high-value care.”
Gastrointestinal and liver diseases incur more than $100 billion in health care expenses annually in the United States, of which more than 60% is related to inpatient care, the researchers noted. However, few studies have comprehensively evaluated the annual burden and costs of hospitalization in patients with chronic gastrointestinal and liver diseases. Therefore, using the Nationwide Readmissions Database, the investigators studied patients with inflammatory bowel disease (IBD), chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases who were hospitalized at least once during the first 6 months of 2013. All patients were diagnosed with IBD, chronic liver diseases, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases and followed for at least 6 months. The researchers stratified hospital days and costs and characterized the subset of patients who fell into the highest decile of days spent in the hospital per month.
The most common reason for hospitalization was chronic liver disease (nearly 377,000 patients), followed by functional gastrointestinal disorders (more than 351,000 patients), gastrointestinal hemorrhage (nearly 191,000 patients), pancreatic diseases (more than 98,000 patients), and IBD (more than 47,000 patients). Patients spent a median of 6-7 days in the hospital per year, with an interquartile range of 3-14 days. Compared with patients in the lowest decile for annual hospital stay (median, 0.13-0.14 days per month), patients in the highest decile spent a median of 3.7-5.1 days in the hospital per month. In this high-cost, high-need subset of patients, the costs of each hospitalization ranged from $7,438 per month to $11,425 per month, and they were typically hospitalized once every 2 months.
“Gastrointestinal diseases, infections, and cardiopulmonary causes were leading reasons for hospitalization of these patients,” the researchers wrote. “At a patient level, modifiable risk factors may include tackling the obesity epidemic and mental health issues and minimizing risk of iatrogenic or health care–associated infections, whereas at a health system level, interventions may include better access to care and connectivity between rural and specialty hospitals.”
Funders included the American College of Gastroenterology, the Crohn’s and Colitis Foundation, and the National Institutes of Health. Senior author Siddharth Singh disclosed unrelated grant funding from Pifzer and AbbVie. The other investigators reported having no conflicts of interest.
SOURCE: Nguyen NH et al. Clin Gastroenterol Hepatol. 2018 Feb 20. doi: 10.1016/j.cgh.2018.02.015.
Understanding the reasons underlying variations in health care utilization is central to any plan to reduce costs at the population level. To this end, Nguyen et al. provide crucial data for the patients for whom we care as gastroenterologists. Studying a longitudinal database of hospitalizations in 2013, the authors provide comprehensive demographic data for the top decile of inpatient health care utilizers (defined by hospital-days/month) with inflammatory bowel disease, chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, and pancreatic diseases. Although constrained by the limits of administrative data and the lack of outpatient/pharmaceutical data linkage, these findings are strengthened by their consistency across conditions. Indeed, despite the heterogeneous disorders surveyed, a remarkably consistent high-need/high-cost "phenotype" emerges: publicly insured, low-income, rural, obese but malnourished, and beset by infections and the complications of diabetes.
What are the next steps?
When a minority of the patients are responsible for a substantial portion of the costs (i.e., the 80/20 rule), one strategy for cost containment is "hot-spotting." Hot-spotting is a two-step process: Identify high-need, high-cost patients, and then deploy interventions tailored to their needs. Nguyen and colleague's work is a landmark for the first step. However, before these findings may be translated into policy or intervention, we need granular data to explain these associations and suggest clear action items. Solutions will likely be multifactorial including early, intensified care for obesity and diabetes (before end-stage complications arise), novel care delivery methods for gastroenterology specialty care in rural hospitals, and intensified outpatient resources for high-need patients in order to coordinate alternatives to hospitalization.
Elliot B. Tapper, MD, is assistant professor, division of gastroenterology and hepatology, University of Michigan, Ann Arbor. He reports consulting for Novartis and receiving unrestricted research grants from Valeant and Gilead, all unrelated to this work.
Understanding the reasons underlying variations in health care utilization is central to any plan to reduce costs at the population level. To this end, Nguyen et al. provide crucial data for the patients for whom we care as gastroenterologists. Studying a longitudinal database of hospitalizations in 2013, the authors provide comprehensive demographic data for the top decile of inpatient health care utilizers (defined by hospital-days/month) with inflammatory bowel disease, chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, and pancreatic diseases. Although constrained by the limits of administrative data and the lack of outpatient/pharmaceutical data linkage, these findings are strengthened by their consistency across conditions. Indeed, despite the heterogeneous disorders surveyed, a remarkably consistent high-need/high-cost "phenotype" emerges: publicly insured, low-income, rural, obese but malnourished, and beset by infections and the complications of diabetes.
What are the next steps?
When a minority of the patients are responsible for a substantial portion of the costs (i.e., the 80/20 rule), one strategy for cost containment is "hot-spotting." Hot-spotting is a two-step process: Identify high-need, high-cost patients, and then deploy interventions tailored to their needs. Nguyen and colleague's work is a landmark for the first step. However, before these findings may be translated into policy or intervention, we need granular data to explain these associations and suggest clear action items. Solutions will likely be multifactorial including early, intensified care for obesity and diabetes (before end-stage complications arise), novel care delivery methods for gastroenterology specialty care in rural hospitals, and intensified outpatient resources for high-need patients in order to coordinate alternatives to hospitalization.
Elliot B. Tapper, MD, is assistant professor, division of gastroenterology and hepatology, University of Michigan, Ann Arbor. He reports consulting for Novartis and receiving unrestricted research grants from Valeant and Gilead, all unrelated to this work.
Understanding the reasons underlying variations in health care utilization is central to any plan to reduce costs at the population level. To this end, Nguyen et al. provide crucial data for the patients for whom we care as gastroenterologists. Studying a longitudinal database of hospitalizations in 2013, the authors provide comprehensive demographic data for the top decile of inpatient health care utilizers (defined by hospital-days/month) with inflammatory bowel disease, chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, and pancreatic diseases. Although constrained by the limits of administrative data and the lack of outpatient/pharmaceutical data linkage, these findings are strengthened by their consistency across conditions. Indeed, despite the heterogeneous disorders surveyed, a remarkably consistent high-need/high-cost "phenotype" emerges: publicly insured, low-income, rural, obese but malnourished, and beset by infections and the complications of diabetes.
What are the next steps?
When a minority of the patients are responsible for a substantial portion of the costs (i.e., the 80/20 rule), one strategy for cost containment is "hot-spotting." Hot-spotting is a two-step process: Identify high-need, high-cost patients, and then deploy interventions tailored to their needs. Nguyen and colleague's work is a landmark for the first step. However, before these findings may be translated into policy or intervention, we need granular data to explain these associations and suggest clear action items. Solutions will likely be multifactorial including early, intensified care for obesity and diabetes (before end-stage complications arise), novel care delivery methods for gastroenterology specialty care in rural hospitals, and intensified outpatient resources for high-need patients in order to coordinate alternatives to hospitalization.
Elliot B. Tapper, MD, is assistant professor, division of gastroenterology and hepatology, University of Michigan, Ann Arbor. He reports consulting for Novartis and receiving unrestricted research grants from Valeant and Gilead, all unrelated to this work.
Among patients hospitalized with gastrointestinal and liver diseases, a clearly identifiable subset uses significantly more health care resources, which incurs significantly greater costs, according to the results of a national database analysis published in the August issue of Clinical Gastroenterology and Hepatology.
Compared with otherwise similar inpatients, these “high-need, high-cost” individuals are significantly more likely to be enrolled in Medicare or Medicaid, to have lower income, to initially be admitted to a large, rural hospital, to have multiple comorbidities, to be obese, or to be hospitalized for infection, said Nghia Nguyen, MD, and his associates. “[A] small fraction of high-need, high-cost patients contribute disproportionately to hospitalization costs,” they wrote. “Population health management directed toward these patients would facilitate high-value care.”
Gastrointestinal and liver diseases incur more than $100 billion in health care expenses annually in the United States, of which more than 60% is related to inpatient care, the researchers noted. However, few studies have comprehensively evaluated the annual burden and costs of hospitalization in patients with chronic gastrointestinal and liver diseases. Therefore, using the Nationwide Readmissions Database, the investigators studied patients with inflammatory bowel disease (IBD), chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases who were hospitalized at least once during the first 6 months of 2013. All patients were diagnosed with IBD, chronic liver diseases, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases and followed for at least 6 months. The researchers stratified hospital days and costs and characterized the subset of patients who fell into the highest decile of days spent in the hospital per month.
The most common reason for hospitalization was chronic liver disease (nearly 377,000 patients), followed by functional gastrointestinal disorders (more than 351,000 patients), gastrointestinal hemorrhage (nearly 191,000 patients), pancreatic diseases (more than 98,000 patients), and IBD (more than 47,000 patients). Patients spent a median of 6-7 days in the hospital per year, with an interquartile range of 3-14 days. Compared with patients in the lowest decile for annual hospital stay (median, 0.13-0.14 days per month), patients in the highest decile spent a median of 3.7-5.1 days in the hospital per month. In this high-cost, high-need subset of patients, the costs of each hospitalization ranged from $7,438 per month to $11,425 per month, and they were typically hospitalized once every 2 months.
“Gastrointestinal diseases, infections, and cardiopulmonary causes were leading reasons for hospitalization of these patients,” the researchers wrote. “At a patient level, modifiable risk factors may include tackling the obesity epidemic and mental health issues and minimizing risk of iatrogenic or health care–associated infections, whereas at a health system level, interventions may include better access to care and connectivity between rural and specialty hospitals.”
Funders included the American College of Gastroenterology, the Crohn’s and Colitis Foundation, and the National Institutes of Health. Senior author Siddharth Singh disclosed unrelated grant funding from Pifzer and AbbVie. The other investigators reported having no conflicts of interest.
SOURCE: Nguyen NH et al. Clin Gastroenterol Hepatol. 2018 Feb 20. doi: 10.1016/j.cgh.2018.02.015.
Among patients hospitalized with gastrointestinal and liver diseases, a clearly identifiable subset uses significantly more health care resources, which incurs significantly greater costs, according to the results of a national database analysis published in the August issue of Clinical Gastroenterology and Hepatology.
Compared with otherwise similar inpatients, these “high-need, high-cost” individuals are significantly more likely to be enrolled in Medicare or Medicaid, to have lower income, to initially be admitted to a large, rural hospital, to have multiple comorbidities, to be obese, or to be hospitalized for infection, said Nghia Nguyen, MD, and his associates. “[A] small fraction of high-need, high-cost patients contribute disproportionately to hospitalization costs,” they wrote. “Population health management directed toward these patients would facilitate high-value care.”
Gastrointestinal and liver diseases incur more than $100 billion in health care expenses annually in the United States, of which more than 60% is related to inpatient care, the researchers noted. However, few studies have comprehensively evaluated the annual burden and costs of hospitalization in patients with chronic gastrointestinal and liver diseases. Therefore, using the Nationwide Readmissions Database, the investigators studied patients with inflammatory bowel disease (IBD), chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases who were hospitalized at least once during the first 6 months of 2013. All patients were diagnosed with IBD, chronic liver diseases, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases and followed for at least 6 months. The researchers stratified hospital days and costs and characterized the subset of patients who fell into the highest decile of days spent in the hospital per month.
The most common reason for hospitalization was chronic liver disease (nearly 377,000 patients), followed by functional gastrointestinal disorders (more than 351,000 patients), gastrointestinal hemorrhage (nearly 191,000 patients), pancreatic diseases (more than 98,000 patients), and IBD (more than 47,000 patients). Patients spent a median of 6-7 days in the hospital per year, with an interquartile range of 3-14 days. Compared with patients in the lowest decile for annual hospital stay (median, 0.13-0.14 days per month), patients in the highest decile spent a median of 3.7-5.1 days in the hospital per month. In this high-cost, high-need subset of patients, the costs of each hospitalization ranged from $7,438 per month to $11,425 per month, and they were typically hospitalized once every 2 months.
“Gastrointestinal diseases, infections, and cardiopulmonary causes were leading reasons for hospitalization of these patients,” the researchers wrote. “At a patient level, modifiable risk factors may include tackling the obesity epidemic and mental health issues and minimizing risk of iatrogenic or health care–associated infections, whereas at a health system level, interventions may include better access to care and connectivity between rural and specialty hospitals.”
Funders included the American College of Gastroenterology, the Crohn’s and Colitis Foundation, and the National Institutes of Health. Senior author Siddharth Singh disclosed unrelated grant funding from Pifzer and AbbVie. The other investigators reported having no conflicts of interest.
SOURCE: Nguyen NH et al. Clin Gastroenterol Hepatol. 2018 Feb 20. doi: 10.1016/j.cgh.2018.02.015.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: For patients with gastrointestinal or liver disease, significant predictors of high need and cost during hospitalization included Medicare or Medicaid insurance, lower income, first hospitalization in a large rural hospital, high comorbidity burden, obesity, and hospitalization for infection.
Major finding: Patients in the highest decile spent a median of 3.7-4.1 days in the hospital per month for all causes. Gastrointestinal disease, infections, and cardiopulmonary morbidity were the most common reasons for hospitalization.
Study details: Analysis of patients with inflammatory bowel disease, chronic liver disease, functional gastrointestinal disorders, gastrointestinal hemorrhage, or pancreatic diseases hospitalized at least once during 2013.
Disclosures: Funders included the American College of Gastroenterology, the Crohn’s and Colitis Foundation, and the National Institutes of Health. Senior author Siddharth Singh disclosed unrelated grant funding from Pifzer and AbbVie. The other investigators reported having no conflicts of interest.
Source: Nguyen NH et al. Clin Gastroenterol Hepatol. 2018 Feb 20. doi: 10.1016/j.cgh.2018.02.015.
AGA Clinical Practice Update: Statins are safe, effective, and important for most patients with liver disease and dyslipidemia
The medications are only contraindicated in patients with decompensated cirrhosis and statin-induced liver injury, Elizabeth Speliotes, MD, PhD, MPH, and her colleagues wrote in an expert review published in Clinical Gastroenterology and Hepatology. In these patients, statin treatment can compound liver damage and should be avoided, wrote Dr. Speliotes and her coauthors.
Because the liver plays a central role in cholesterol production, many clinicians shy away from treating hyperlipidemia in patients with liver disease. But studies consistently show that lipid-lowering drugs improve dyslipidemia in these patients, which significantly improves both high- and low-density lipoproteins and thereby reduces the long-term risk of cardiovascular disease, the authors wrote.
“Furthermore, the liver plays a role in the metabolism of many drugs, including those that are used to treat dyslipidemia,” wrote Dr. Speliotes of the University of Michigan, Ann Arbor. “It is not surprising, therefore, that many practitioners are hesitant to prescribe medicines to treat dyslipidemia in the setting of liver disease.”
Cholesterol targets described in the 2013 American College of Cardiology/American Heart Association guidelines can safely be applied to patients with liver disease. “The guidelines recommend that adults with cardiovascular disease or LDL of 190 mg/dL or higher be treated with high-intensity statins with the goal of reducing LDL levels by 50%,” they said. Patients whose LDL is 189 mg/dL or lower will benefit from moderate-intensity statins, with a target of a 30%-50% decrease in LDL.
The authors described best practice advice for dyslipidemia treatment in six liver diseases: drug-induced liver injury (DILI), nonalcoholic fatty liver disease (NAFLD), viral hepatitis B and C (HBV and HCV), primary biliary cholangitis (PBC), cirrhosis, and posttransplant dyslipidemia.
DILI
DILI is characterized by elevations of threefold or more in serum alanine aminotransferase (ALT) or aspartate aminotransferase and at least a doubling of total serum bilirubin with no other identifiable cause of these aberrations except the suspect drug. Statins rarely cause a DILI (1 in 100,000 patients), but can cause transient, benign ALT elevations. Statins should be discontinued if ALT or aspartate aminotransferase levels exceed a tripling of the upper limit of normal with concomitant bilirubin elevations. They should not be prescribed to patients with acute liver failure or decompensated liver disease, but otherwise they are safe for most patients with liver disease.
NAFLD
Many patients with NAFLD also have dyslipidemia. All NAFLD patients have an increased risk of cardiovascular disease, although NAFLD and nonalcoholic steatohepatitis are not traditional cardiovascular risk factors. Nevertheless, statins and the accompanying improvement in dyslipidemia have been shown to decrease cardiovascular mortality in these patients. The IDEAL study, for example, showed that moderate statin treatment with 80 mg atorvastatin was associated with a 44% decreased risk in secondary cardiovascular events. Other studies show similar results.
NAFLD patients with elevated LDL may benefit from ezetimibe as primary or add-on therapy. However, none of the drugs used to treat dyslipidemia will improve NAFLD or nonalcoholic steatohepatitis histology.
Viral hepatitis
Hepatitis C virus
Patients with HCV infection often experience decreased serum LDL and total cholesterol. However, these are virally mediated and don’t confer cardiovascular protection. In fact, HCV infections are associated with an increased risk of myocardial infarction. If the patient spontaneously clears the virus, lipids may rebound, so levels should be regularly monitored even if the patient does not need statin therapy.
Hepatitis B virus
HBV also interacts with lipid metabolism and can lead to hyperlipidemia. The American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment and statin therapy apply to these patients. Statins are safe in patients with either HCV or HBV, who tolerate them well.
PBC
PBC is a chronic autoimmune inflammatory cholestatic disease that is associated with dyslipidemia. These patients exhibit increased serum triglyceride and HDL levels that vary according to PBC stage. About 10% have a significant risk of cardiovascular disease. PBC patients with compensated liver disease can safely tolerate statin treatment, but the drugs should not be given to PBC patients with decompensated liver disease.
Obeticholic acid (OCA) is sometimes used as second-line therapy for PBC; it affects genes that regulate bile acid synthesis, transport, and action. However, the POISE study showed that, while OCA improved PBC symptoms, it was associated with an increase in LDL and total cholesterol and a decrease in HDL. No follow-up studies have determined cardiovascular implications of that change, but OCA should be avoided in patients with active cardiovascular disease or with cardiovascular risk factors.
Cirrhosis
Recent work suggests that patients with cirrhosis may face a higher risk of coronary artery disease than was previously thought, although that risk varies widely according to the etiology of the cirrhosis.
Statins are safe and effective in patients with Child-Pugh class A cirrhosis; there are few data on their safety in patients with decompensated cirrhosis. Some guidance for these patients exists in the 2014 recommendations of the Liver Expert Panel, which advised against statin use in patients with Child-Pugh class B or C cirrhosis.
There’s some evidence that statins reduce portal pressure and may reduce the risk of decompensation in patients whose cirrhosis is caused by HCV or HBV infections, but they should not be used for this purpose.
Posttransplant dyslipidemia
After liver transplant, more than 60% of patients will develop dyslipidemia; these patients often have obesity or diabetes.
Statins are safe for patients with liver transplant. Concomitant use of calcineurin inhibitors and statins that are metabolized by cytochrome P450 may increase the risk of statin-associated myopathy. Pravastatin and fluvastatin are preferable, because they are metabolized by cytochrome P450 34A.
Neither Dr. Speliotes nor her coauthors had any financial disclosures.
SOURCE: Speliotes EK et al. Clin Gastroenterol Hepatol. 2018 Apr 21. doi: 10.1016/j.cgh.2018.04.023.
The medications are only contraindicated in patients with decompensated cirrhosis and statin-induced liver injury, Elizabeth Speliotes, MD, PhD, MPH, and her colleagues wrote in an expert review published in Clinical Gastroenterology and Hepatology. In these patients, statin treatment can compound liver damage and should be avoided, wrote Dr. Speliotes and her coauthors.
Because the liver plays a central role in cholesterol production, many clinicians shy away from treating hyperlipidemia in patients with liver disease. But studies consistently show that lipid-lowering drugs improve dyslipidemia in these patients, which significantly improves both high- and low-density lipoproteins and thereby reduces the long-term risk of cardiovascular disease, the authors wrote.
“Furthermore, the liver plays a role in the metabolism of many drugs, including those that are used to treat dyslipidemia,” wrote Dr. Speliotes of the University of Michigan, Ann Arbor. “It is not surprising, therefore, that many practitioners are hesitant to prescribe medicines to treat dyslipidemia in the setting of liver disease.”
Cholesterol targets described in the 2013 American College of Cardiology/American Heart Association guidelines can safely be applied to patients with liver disease. “The guidelines recommend that adults with cardiovascular disease or LDL of 190 mg/dL or higher be treated with high-intensity statins with the goal of reducing LDL levels by 50%,” they said. Patients whose LDL is 189 mg/dL or lower will benefit from moderate-intensity statins, with a target of a 30%-50% decrease in LDL.
The authors described best practice advice for dyslipidemia treatment in six liver diseases: drug-induced liver injury (DILI), nonalcoholic fatty liver disease (NAFLD), viral hepatitis B and C (HBV and HCV), primary biliary cholangitis (PBC), cirrhosis, and posttransplant dyslipidemia.
DILI
DILI is characterized by elevations of threefold or more in serum alanine aminotransferase (ALT) or aspartate aminotransferase and at least a doubling of total serum bilirubin with no other identifiable cause of these aberrations except the suspect drug. Statins rarely cause a DILI (1 in 100,000 patients), but can cause transient, benign ALT elevations. Statins should be discontinued if ALT or aspartate aminotransferase levels exceed a tripling of the upper limit of normal with concomitant bilirubin elevations. They should not be prescribed to patients with acute liver failure or decompensated liver disease, but otherwise they are safe for most patients with liver disease.
NAFLD
Many patients with NAFLD also have dyslipidemia. All NAFLD patients have an increased risk of cardiovascular disease, although NAFLD and nonalcoholic steatohepatitis are not traditional cardiovascular risk factors. Nevertheless, statins and the accompanying improvement in dyslipidemia have been shown to decrease cardiovascular mortality in these patients. The IDEAL study, for example, showed that moderate statin treatment with 80 mg atorvastatin was associated with a 44% decreased risk in secondary cardiovascular events. Other studies show similar results.
NAFLD patients with elevated LDL may benefit from ezetimibe as primary or add-on therapy. However, none of the drugs used to treat dyslipidemia will improve NAFLD or nonalcoholic steatohepatitis histology.
Viral hepatitis
Hepatitis C virus
Patients with HCV infection often experience decreased serum LDL and total cholesterol. However, these are virally mediated and don’t confer cardiovascular protection. In fact, HCV infections are associated with an increased risk of myocardial infarction. If the patient spontaneously clears the virus, lipids may rebound, so levels should be regularly monitored even if the patient does not need statin therapy.
Hepatitis B virus
HBV also interacts with lipid metabolism and can lead to hyperlipidemia. The American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment and statin therapy apply to these patients. Statins are safe in patients with either HCV or HBV, who tolerate them well.
PBC
PBC is a chronic autoimmune inflammatory cholestatic disease that is associated with dyslipidemia. These patients exhibit increased serum triglyceride and HDL levels that vary according to PBC stage. About 10% have a significant risk of cardiovascular disease. PBC patients with compensated liver disease can safely tolerate statin treatment, but the drugs should not be given to PBC patients with decompensated liver disease.
Obeticholic acid (OCA) is sometimes used as second-line therapy for PBC; it affects genes that regulate bile acid synthesis, transport, and action. However, the POISE study showed that, while OCA improved PBC symptoms, it was associated with an increase in LDL and total cholesterol and a decrease in HDL. No follow-up studies have determined cardiovascular implications of that change, but OCA should be avoided in patients with active cardiovascular disease or with cardiovascular risk factors.
Cirrhosis
Recent work suggests that patients with cirrhosis may face a higher risk of coronary artery disease than was previously thought, although that risk varies widely according to the etiology of the cirrhosis.
Statins are safe and effective in patients with Child-Pugh class A cirrhosis; there are few data on their safety in patients with decompensated cirrhosis. Some guidance for these patients exists in the 2014 recommendations of the Liver Expert Panel, which advised against statin use in patients with Child-Pugh class B or C cirrhosis.
There’s some evidence that statins reduce portal pressure and may reduce the risk of decompensation in patients whose cirrhosis is caused by HCV or HBV infections, but they should not be used for this purpose.
Posttransplant dyslipidemia
After liver transplant, more than 60% of patients will develop dyslipidemia; these patients often have obesity or diabetes.
Statins are safe for patients with liver transplant. Concomitant use of calcineurin inhibitors and statins that are metabolized by cytochrome P450 may increase the risk of statin-associated myopathy. Pravastatin and fluvastatin are preferable, because they are metabolized by cytochrome P450 34A.
Neither Dr. Speliotes nor her coauthors had any financial disclosures.
SOURCE: Speliotes EK et al. Clin Gastroenterol Hepatol. 2018 Apr 21. doi: 10.1016/j.cgh.2018.04.023.
The medications are only contraindicated in patients with decompensated cirrhosis and statin-induced liver injury, Elizabeth Speliotes, MD, PhD, MPH, and her colleagues wrote in an expert review published in Clinical Gastroenterology and Hepatology. In these patients, statin treatment can compound liver damage and should be avoided, wrote Dr. Speliotes and her coauthors.
Because the liver plays a central role in cholesterol production, many clinicians shy away from treating hyperlipidemia in patients with liver disease. But studies consistently show that lipid-lowering drugs improve dyslipidemia in these patients, which significantly improves both high- and low-density lipoproteins and thereby reduces the long-term risk of cardiovascular disease, the authors wrote.
“Furthermore, the liver plays a role in the metabolism of many drugs, including those that are used to treat dyslipidemia,” wrote Dr. Speliotes of the University of Michigan, Ann Arbor. “It is not surprising, therefore, that many practitioners are hesitant to prescribe medicines to treat dyslipidemia in the setting of liver disease.”
Cholesterol targets described in the 2013 American College of Cardiology/American Heart Association guidelines can safely be applied to patients with liver disease. “The guidelines recommend that adults with cardiovascular disease or LDL of 190 mg/dL or higher be treated with high-intensity statins with the goal of reducing LDL levels by 50%,” they said. Patients whose LDL is 189 mg/dL or lower will benefit from moderate-intensity statins, with a target of a 30%-50% decrease in LDL.
The authors described best practice advice for dyslipidemia treatment in six liver diseases: drug-induced liver injury (DILI), nonalcoholic fatty liver disease (NAFLD), viral hepatitis B and C (HBV and HCV), primary biliary cholangitis (PBC), cirrhosis, and posttransplant dyslipidemia.
DILI
DILI is characterized by elevations of threefold or more in serum alanine aminotransferase (ALT) or aspartate aminotransferase and at least a doubling of total serum bilirubin with no other identifiable cause of these aberrations except the suspect drug. Statins rarely cause a DILI (1 in 100,000 patients), but can cause transient, benign ALT elevations. Statins should be discontinued if ALT or aspartate aminotransferase levels exceed a tripling of the upper limit of normal with concomitant bilirubin elevations. They should not be prescribed to patients with acute liver failure or decompensated liver disease, but otherwise they are safe for most patients with liver disease.
NAFLD
Many patients with NAFLD also have dyslipidemia. All NAFLD patients have an increased risk of cardiovascular disease, although NAFLD and nonalcoholic steatohepatitis are not traditional cardiovascular risk factors. Nevertheless, statins and the accompanying improvement in dyslipidemia have been shown to decrease cardiovascular mortality in these patients. The IDEAL study, for example, showed that moderate statin treatment with 80 mg atorvastatin was associated with a 44% decreased risk in secondary cardiovascular events. Other studies show similar results.
NAFLD patients with elevated LDL may benefit from ezetimibe as primary or add-on therapy. However, none of the drugs used to treat dyslipidemia will improve NAFLD or nonalcoholic steatohepatitis histology.
Viral hepatitis
Hepatitis C virus
Patients with HCV infection often experience decreased serum LDL and total cholesterol. However, these are virally mediated and don’t confer cardiovascular protection. In fact, HCV infections are associated with an increased risk of myocardial infarction. If the patient spontaneously clears the virus, lipids may rebound, so levels should be regularly monitored even if the patient does not need statin therapy.
Hepatitis B virus
HBV also interacts with lipid metabolism and can lead to hyperlipidemia. The American College of Cardiology/American Heart Association guidelines for cardiovascular risk assessment and statin therapy apply to these patients. Statins are safe in patients with either HCV or HBV, who tolerate them well.
PBC
PBC is a chronic autoimmune inflammatory cholestatic disease that is associated with dyslipidemia. These patients exhibit increased serum triglyceride and HDL levels that vary according to PBC stage. About 10% have a significant risk of cardiovascular disease. PBC patients with compensated liver disease can safely tolerate statin treatment, but the drugs should not be given to PBC patients with decompensated liver disease.
Obeticholic acid (OCA) is sometimes used as second-line therapy for PBC; it affects genes that regulate bile acid synthesis, transport, and action. However, the POISE study showed that, while OCA improved PBC symptoms, it was associated with an increase in LDL and total cholesterol and a decrease in HDL. No follow-up studies have determined cardiovascular implications of that change, but OCA should be avoided in patients with active cardiovascular disease or with cardiovascular risk factors.
Cirrhosis
Recent work suggests that patients with cirrhosis may face a higher risk of coronary artery disease than was previously thought, although that risk varies widely according to the etiology of the cirrhosis.
Statins are safe and effective in patients with Child-Pugh class A cirrhosis; there are few data on their safety in patients with decompensated cirrhosis. Some guidance for these patients exists in the 2014 recommendations of the Liver Expert Panel, which advised against statin use in patients with Child-Pugh class B or C cirrhosis.
There’s some evidence that statins reduce portal pressure and may reduce the risk of decompensation in patients whose cirrhosis is caused by HCV or HBV infections, but they should not be used for this purpose.
Posttransplant dyslipidemia
After liver transplant, more than 60% of patients will develop dyslipidemia; these patients often have obesity or diabetes.
Statins are safe for patients with liver transplant. Concomitant use of calcineurin inhibitors and statins that are metabolized by cytochrome P450 may increase the risk of statin-associated myopathy. Pravastatin and fluvastatin are preferable, because they are metabolized by cytochrome P450 34A.
Neither Dr. Speliotes nor her coauthors had any financial disclosures.
SOURCE: Speliotes EK et al. Clin Gastroenterol Hepatol. 2018 Apr 21. doi: 10.1016/j.cgh.2018.04.023.
EXPERT ANALYSIS FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA CPU: Extraesophageal symptoms attributed to GERD
When patients lack typical symptoms of gastroesophageal reflux disease (GERD) and have extraesophageal symptoms, ENT, allergy, and pulmonary work-ups are “essential and often should be performed initially,” experts note in an American Gastroenterological Association clinical practice update.
Extraesophageal symptoms often are unrelated to GERD or are multifactorial, wrote Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates in Clinical Gastroenterology and Hepatology. Gastroenterologists often are asked to look for reflux as the cause of extraesophageal symptoms before other etiologies have been ruled out.
Proposed extraesophageal manifestations of GERD range from chronic throat clearing and dysphonia to otitis, pulmonary fibrosis, laryngeal cancer, and even lung transplant rejection. Stronger evidence links GERD with symptoms of asthma, cough, and hoarseness, the experts note. “When less stringent criteria are used, the attributions are broader and could include sore throat, sinusitis, ear pain, and pulmonary fibrosis.”
When asked to assess whether GERD is causing extraesophageal symptoms, consider the “constellation” of patient presentation, test results, and treatment response, according to the clinical practice update. No diagnostic tests “unequivocally link any suspected extraesophageal symptom to GERD.” For patients who have both extraesophageal symptoms and typical symptoms of GERD, the authors suggest an evaluator regimen of 6-8 weeks of empiric, aggressive (twice-daily) proton pump inhibitor (PPI) therapy. If aggressive acid suppression therapy appears to improve extraesophageal symptoms, patients should be titrated to the lowest effective treatment dose.If symptoms persist despite an aggressive trial of a PPI, and patients have a body mass index under 25, and a seemingly low probability of GERD, then the experts recommend pH testing “off” therapy and seeking other etiologies for extraesophageal symptoms. If symptoms persist and a patients’ BMI exceeds 25 with a high suspicion of GERD, they recommend evaluations for concomitant asthma or lung disease. If these work-ups are positive, they recommend multichannel intraluminal impedance testing or pH monitoring on treatment.
The clinical practice update strongly discourages surgical treatment of extraesophageal GERD symptoms except in specific populations, such as when patients have objective signs of treatment-refractory GERD and have not responded to comprehensive therapy for other possible causes of extraesophageal symptoms. Recent data suggest that surgery can benefit patients with confirmed structural defects, such as hiatal hernia, which are causing symptomatic, volume-based regurgitation, the experts note. Ideally, these patients should first undergo pH and impedance monitoring to objectively measure the effects of reflux. Additionally, surgical fundoplication “might be beneficial” for patients whose extraesophageal symptoms clearly have responded to PPI therapy but who refuse long-term PPI therapy or who develop unacceptable side effects.
The practice update also extensively discusses the role of testing to evaluate the role of GERD in extraesophageal symptoms. Barium esophagography is insensitive for GERD and is useful only for evaluating dysphagia and the size and type of a hiatal hernia, the experts note. Abnormal laryngoscopy or pharyngoscopic findings are more useful but should not be the “initial driving force” behind a GERD diagnosis and do not necessarily link GERD to extraesophageal symptoms. Likewise, esophagogastroduodenoscopy can identify esophagitis, which signifies GERD but does not establish it as etiologic.
Positive ambulatory pH or impedance monitoring or pharyngeal pH tests also do not definitively link reflux to suspected extraesophageal symptoms, the experts note. They suggest considering “on” therapy monitoring to evaluate treatment efficacy and to time reflux events relative to symptoms in patients with esophagitis, Barrett’s esophagus, or a large hiatal hernia. Conversely, they recommend considering “off” treatment testing to rule out GERD in patients who have no history of confirmed or suspected reflux and who have not responded to PPI therapy.
Novel tests, such as salivary pepsin and mucosal impedance, have “no clear role in establishing GERD as the cause of extraesophageal symptoms,” the experts emphasize. Clinician scientists also debate the exact pathophysiology of extraesophageal GERD sequelae. While chronic exposure to gastric refluxate clearly can harm proximal structures such as the pharynx, larynx, and bronchial tree, it remains unclear how much acid is necessary to cause injury and whether bile, pepsin, or neurogenic stimulation play a role.
Dr. Vaezi reported having no conflicts of interest. Senior author Frank Zerbib, MD, PhD, reported receiving devices for research purposes from Medtronic and Sandhill Scientific.
SOURCE: Vaezi MF et al. Clin Gastroenterol Hepatol. 2018 Feb 7. doi: 10.1016/j.cgh.2018.02.001.
When patients lack typical symptoms of gastroesophageal reflux disease (GERD) and have extraesophageal symptoms, ENT, allergy, and pulmonary work-ups are “essential and often should be performed initially,” experts note in an American Gastroenterological Association clinical practice update.
Extraesophageal symptoms often are unrelated to GERD or are multifactorial, wrote Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates in Clinical Gastroenterology and Hepatology. Gastroenterologists often are asked to look for reflux as the cause of extraesophageal symptoms before other etiologies have been ruled out.
Proposed extraesophageal manifestations of GERD range from chronic throat clearing and dysphonia to otitis, pulmonary fibrosis, laryngeal cancer, and even lung transplant rejection. Stronger evidence links GERD with symptoms of asthma, cough, and hoarseness, the experts note. “When less stringent criteria are used, the attributions are broader and could include sore throat, sinusitis, ear pain, and pulmonary fibrosis.”
When asked to assess whether GERD is causing extraesophageal symptoms, consider the “constellation” of patient presentation, test results, and treatment response, according to the clinical practice update. No diagnostic tests “unequivocally link any suspected extraesophageal symptom to GERD.” For patients who have both extraesophageal symptoms and typical symptoms of GERD, the authors suggest an evaluator regimen of 6-8 weeks of empiric, aggressive (twice-daily) proton pump inhibitor (PPI) therapy. If aggressive acid suppression therapy appears to improve extraesophageal symptoms, patients should be titrated to the lowest effective treatment dose.If symptoms persist despite an aggressive trial of a PPI, and patients have a body mass index under 25, and a seemingly low probability of GERD, then the experts recommend pH testing “off” therapy and seeking other etiologies for extraesophageal symptoms. If symptoms persist and a patients’ BMI exceeds 25 with a high suspicion of GERD, they recommend evaluations for concomitant asthma or lung disease. If these work-ups are positive, they recommend multichannel intraluminal impedance testing or pH monitoring on treatment.
The clinical practice update strongly discourages surgical treatment of extraesophageal GERD symptoms except in specific populations, such as when patients have objective signs of treatment-refractory GERD and have not responded to comprehensive therapy for other possible causes of extraesophageal symptoms. Recent data suggest that surgery can benefit patients with confirmed structural defects, such as hiatal hernia, which are causing symptomatic, volume-based regurgitation, the experts note. Ideally, these patients should first undergo pH and impedance monitoring to objectively measure the effects of reflux. Additionally, surgical fundoplication “might be beneficial” for patients whose extraesophageal symptoms clearly have responded to PPI therapy but who refuse long-term PPI therapy or who develop unacceptable side effects.
The practice update also extensively discusses the role of testing to evaluate the role of GERD in extraesophageal symptoms. Barium esophagography is insensitive for GERD and is useful only for evaluating dysphagia and the size and type of a hiatal hernia, the experts note. Abnormal laryngoscopy or pharyngoscopic findings are more useful but should not be the “initial driving force” behind a GERD diagnosis and do not necessarily link GERD to extraesophageal symptoms. Likewise, esophagogastroduodenoscopy can identify esophagitis, which signifies GERD but does not establish it as etiologic.
Positive ambulatory pH or impedance monitoring or pharyngeal pH tests also do not definitively link reflux to suspected extraesophageal symptoms, the experts note. They suggest considering “on” therapy monitoring to evaluate treatment efficacy and to time reflux events relative to symptoms in patients with esophagitis, Barrett’s esophagus, or a large hiatal hernia. Conversely, they recommend considering “off” treatment testing to rule out GERD in patients who have no history of confirmed or suspected reflux and who have not responded to PPI therapy.
Novel tests, such as salivary pepsin and mucosal impedance, have “no clear role in establishing GERD as the cause of extraesophageal symptoms,” the experts emphasize. Clinician scientists also debate the exact pathophysiology of extraesophageal GERD sequelae. While chronic exposure to gastric refluxate clearly can harm proximal structures such as the pharynx, larynx, and bronchial tree, it remains unclear how much acid is necessary to cause injury and whether bile, pepsin, or neurogenic stimulation play a role.
Dr. Vaezi reported having no conflicts of interest. Senior author Frank Zerbib, MD, PhD, reported receiving devices for research purposes from Medtronic and Sandhill Scientific.
SOURCE: Vaezi MF et al. Clin Gastroenterol Hepatol. 2018 Feb 7. doi: 10.1016/j.cgh.2018.02.001.
When patients lack typical symptoms of gastroesophageal reflux disease (GERD) and have extraesophageal symptoms, ENT, allergy, and pulmonary work-ups are “essential and often should be performed initially,” experts note in an American Gastroenterological Association clinical practice update.
Extraesophageal symptoms often are unrelated to GERD or are multifactorial, wrote Michael F. Vaezi, MD, PhD, of Vanderbilt University Medical Center in Nashville, Tenn., and his associates in Clinical Gastroenterology and Hepatology. Gastroenterologists often are asked to look for reflux as the cause of extraesophageal symptoms before other etiologies have been ruled out.
Proposed extraesophageal manifestations of GERD range from chronic throat clearing and dysphonia to otitis, pulmonary fibrosis, laryngeal cancer, and even lung transplant rejection. Stronger evidence links GERD with symptoms of asthma, cough, and hoarseness, the experts note. “When less stringent criteria are used, the attributions are broader and could include sore throat, sinusitis, ear pain, and pulmonary fibrosis.”
When asked to assess whether GERD is causing extraesophageal symptoms, consider the “constellation” of patient presentation, test results, and treatment response, according to the clinical practice update. No diagnostic tests “unequivocally link any suspected extraesophageal symptom to GERD.” For patients who have both extraesophageal symptoms and typical symptoms of GERD, the authors suggest an evaluator regimen of 6-8 weeks of empiric, aggressive (twice-daily) proton pump inhibitor (PPI) therapy. If aggressive acid suppression therapy appears to improve extraesophageal symptoms, patients should be titrated to the lowest effective treatment dose.If symptoms persist despite an aggressive trial of a PPI, and patients have a body mass index under 25, and a seemingly low probability of GERD, then the experts recommend pH testing “off” therapy and seeking other etiologies for extraesophageal symptoms. If symptoms persist and a patients’ BMI exceeds 25 with a high suspicion of GERD, they recommend evaluations for concomitant asthma or lung disease. If these work-ups are positive, they recommend multichannel intraluminal impedance testing or pH monitoring on treatment.
The clinical practice update strongly discourages surgical treatment of extraesophageal GERD symptoms except in specific populations, such as when patients have objective signs of treatment-refractory GERD and have not responded to comprehensive therapy for other possible causes of extraesophageal symptoms. Recent data suggest that surgery can benefit patients with confirmed structural defects, such as hiatal hernia, which are causing symptomatic, volume-based regurgitation, the experts note. Ideally, these patients should first undergo pH and impedance monitoring to objectively measure the effects of reflux. Additionally, surgical fundoplication “might be beneficial” for patients whose extraesophageal symptoms clearly have responded to PPI therapy but who refuse long-term PPI therapy or who develop unacceptable side effects.
The practice update also extensively discusses the role of testing to evaluate the role of GERD in extraesophageal symptoms. Barium esophagography is insensitive for GERD and is useful only for evaluating dysphagia and the size and type of a hiatal hernia, the experts note. Abnormal laryngoscopy or pharyngoscopic findings are more useful but should not be the “initial driving force” behind a GERD diagnosis and do not necessarily link GERD to extraesophageal symptoms. Likewise, esophagogastroduodenoscopy can identify esophagitis, which signifies GERD but does not establish it as etiologic.
Positive ambulatory pH or impedance monitoring or pharyngeal pH tests also do not definitively link reflux to suspected extraesophageal symptoms, the experts note. They suggest considering “on” therapy monitoring to evaluate treatment efficacy and to time reflux events relative to symptoms in patients with esophagitis, Barrett’s esophagus, or a large hiatal hernia. Conversely, they recommend considering “off” treatment testing to rule out GERD in patients who have no history of confirmed or suspected reflux and who have not responded to PPI therapy.
Novel tests, such as salivary pepsin and mucosal impedance, have “no clear role in establishing GERD as the cause of extraesophageal symptoms,” the experts emphasize. Clinician scientists also debate the exact pathophysiology of extraesophageal GERD sequelae. While chronic exposure to gastric refluxate clearly can harm proximal structures such as the pharynx, larynx, and bronchial tree, it remains unclear how much acid is necessary to cause injury and whether bile, pepsin, or neurogenic stimulation play a role.
Dr. Vaezi reported having no conflicts of interest. Senior author Frank Zerbib, MD, PhD, reported receiving devices for research purposes from Medtronic and Sandhill Scientific.
SOURCE: Vaezi MF et al. Clin Gastroenterol Hepatol. 2018 Feb 7. doi: 10.1016/j.cgh.2018.02.001.
Home-based CBT significantly improved IBS symptoms
Primarily home-based cognitive-behavioral therapy improved irritable bowel syndrome symptoms at least as much as conventional CBT, cut clinician time by 60%, and significantly outperformed educational sessions in a multicenter clinical trial reported in the July issue of Gastroenterology.
Acutely, primarily home-based CBT produced a mean 61% improvement in self-reported symptoms on the IBS version of the Clinical Global Impressions Scale, versus 44% for the educational control group (P less than .05), wrote Jeffrey M. Lackner, PsyD, of the State University of New York at Buffalo and his associates. Blinded gastroenterologists reported improvements of 56% and 40%, respectively (P less than .05). The superiority of the minimal-contact CBT program held up at 6 months and equivalence tests found it “at least as effective as standard CBT,” the researchers wrote.
IBS is a major area of unmet clinical need that costs the United States some $28 billion annually. Clinicians and patients lack both reliable biomarkers and “uniformly effective” therapies, the investigators noted. In recent years, severe adverse events have greatly restricted the availability of otherwise promising Food and Drug Administration–approved therapies, such as Lotronex (alosetron hydrochlorine), which has been linked to ischemic colitis and fatal cases of ruptured bowel, and Zelnorm (tegaserod maleate), which has been associated with myocardial infarction, stroke, and unstable angina.
In contrast, face-to-face CBT is safe, efficacious, and guideline recommended for IBS. However, uptake is limited by cost, stigma, geography, and a shortage of certified providers, the researchers noted. They enrolled 436 patients with IBS based on Rome III criteria and randomly assigned them to one of three interventions. The standard CBT group received 10 weekly, 60-minute, face-to-face CBT sessions on brain-gut interactions, symptom triggers and monitoring, muscle relaxation, worry control, problem-solving, and relapse prevention. The primarily home-based CBT group covered the same topics but attended only four clinic sessions and was provided home study materials. Finally, the education group attended four sessions with background information on IBS and the role of stress, diet, and exercise.
Baseline characteristics were comparable among groups, as were dropout rates (9% overall). In all, 89% of patients completed at least 8 of 10 standard cognitive-behavioral therapy sessions or at least three of four home-based CBT or educational sessions. Six months after the interventions ended, primarily home-based CBT continued to outperform education (blinded gastroenterologist-reported improvements, 58.4% and 44.8%, respectively; P = .05 for difference between groups).
Equivalence tests indicated that the minimal-CBT intervention was at least as effective as standard CBT, and improvements were not primarily the result of concomitant medications, according to the researchers. Nonetheless, only 42% of patients who benefited from CBT achieved remission, defined as no or mild IBS symptoms on the gastroenterologist-administered Clinical Global Impressions Scale. Unremitted patients might benefit from combining CBT with medical therapies that target both “central and peripheral mechanisms of IBS,” the investigators said.
The three interventions produced comparable acute and longer-term improvements on the IBS Symptom Severity Scale, which emphasizes sensory symptoms and therefore might be a less sensitive endpoint than the Clinical Global Impressions Scale, the researchers noted. Nonetheless, CBT produced some of the strongest absolute symptomatic improvements ever reported for IBS. “To put these data in context, treatment response of FDA-approved pharmacological agents using global IBS symptom improvement scales range from 17% to 40%,” the researchers wrote.
The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
SOURCE: Lackner JM et al. Gastroenterology. 2018 Apr 24. doi: 10.1053/j.gastro.2018.03.063.
Treating the myriad symptoms of irritable bowel syndrome (IBS) patients remains a great challenge in clinical practice. A bigger challenge is the management of IBS patients who are refractory to medical therapy, which commonly includes a combination of pain, bowel, and psychiatric medications. In this very well designed and executed study, Lackner and his colleagues randomized refractory IBS patients with moderate to severe symptoms to three therapeutic arms: standard cognitive-behavioral therapy (CBT), minimal-contact home-based CBT, and IBS education. The authors demonstrated that 4-session home-based CBT was as efficacious as 10 sessions of standard CBT and both were significantly more efficacious than IBS education in global improvement of IBS symptoms. The superior effect of both types of CBT was maintained over a period of 6 months post treatment.
There are several important conclusions from this pivotal trial. First, the study further cemented the therapeutic value of CBT in the management of IBS patients, especially for those patients who are refractory to the currently available medical therapy. Because of the size of the study and the rigorous design, it is probably the best evidence we currently have about the value of CBT in IBS. Second, minimal-contact home-based CBT is as effective as standard CBT in controlling the full range of IBS symptoms. The former may be preferred by IBS patients, who are not available or may not be compliant with repeated clinic visits for standard CBT sessions. Standard CBT is typically lengthy and expensive. The minimal-contact home-based CBT option has the benefit of being more accessible and less costly, and most importantly, it does so in a way that does not compromise the therapeutic value of symptom relief.
The exact duration of symptom control that can be achieved post CBT and the value of other psychological interventions in IBS patients remain to be elucidated.
Ronnie Fass, MD, is a professor of medicine at Case Western Reserve University, Cleveland, as well as the medical director of the Digestive Health Center and director of the division of gastroenterology and hepatology, head, esophageal and swallowing center at MetroHealth Medical Center, also in Cleveland. He has no conflicts of interest.
Treating the myriad symptoms of irritable bowel syndrome (IBS) patients remains a great challenge in clinical practice. A bigger challenge is the management of IBS patients who are refractory to medical therapy, which commonly includes a combination of pain, bowel, and psychiatric medications. In this very well designed and executed study, Lackner and his colleagues randomized refractory IBS patients with moderate to severe symptoms to three therapeutic arms: standard cognitive-behavioral therapy (CBT), minimal-contact home-based CBT, and IBS education. The authors demonstrated that 4-session home-based CBT was as efficacious as 10 sessions of standard CBT and both were significantly more efficacious than IBS education in global improvement of IBS symptoms. The superior effect of both types of CBT was maintained over a period of 6 months post treatment.
There are several important conclusions from this pivotal trial. First, the study further cemented the therapeutic value of CBT in the management of IBS patients, especially for those patients who are refractory to the currently available medical therapy. Because of the size of the study and the rigorous design, it is probably the best evidence we currently have about the value of CBT in IBS. Second, minimal-contact home-based CBT is as effective as standard CBT in controlling the full range of IBS symptoms. The former may be preferred by IBS patients, who are not available or may not be compliant with repeated clinic visits for standard CBT sessions. Standard CBT is typically lengthy and expensive. The minimal-contact home-based CBT option has the benefit of being more accessible and less costly, and most importantly, it does so in a way that does not compromise the therapeutic value of symptom relief.
The exact duration of symptom control that can be achieved post CBT and the value of other psychological interventions in IBS patients remain to be elucidated.
Ronnie Fass, MD, is a professor of medicine at Case Western Reserve University, Cleveland, as well as the medical director of the Digestive Health Center and director of the division of gastroenterology and hepatology, head, esophageal and swallowing center at MetroHealth Medical Center, also in Cleveland. He has no conflicts of interest.
Treating the myriad symptoms of irritable bowel syndrome (IBS) patients remains a great challenge in clinical practice. A bigger challenge is the management of IBS patients who are refractory to medical therapy, which commonly includes a combination of pain, bowel, and psychiatric medications. In this very well designed and executed study, Lackner and his colleagues randomized refractory IBS patients with moderate to severe symptoms to three therapeutic arms: standard cognitive-behavioral therapy (CBT), minimal-contact home-based CBT, and IBS education. The authors demonstrated that 4-session home-based CBT was as efficacious as 10 sessions of standard CBT and both were significantly more efficacious than IBS education in global improvement of IBS symptoms. The superior effect of both types of CBT was maintained over a period of 6 months post treatment.
There are several important conclusions from this pivotal trial. First, the study further cemented the therapeutic value of CBT in the management of IBS patients, especially for those patients who are refractory to the currently available medical therapy. Because of the size of the study and the rigorous design, it is probably the best evidence we currently have about the value of CBT in IBS. Second, minimal-contact home-based CBT is as effective as standard CBT in controlling the full range of IBS symptoms. The former may be preferred by IBS patients, who are not available or may not be compliant with repeated clinic visits for standard CBT sessions. Standard CBT is typically lengthy and expensive. The minimal-contact home-based CBT option has the benefit of being more accessible and less costly, and most importantly, it does so in a way that does not compromise the therapeutic value of symptom relief.
The exact duration of symptom control that can be achieved post CBT and the value of other psychological interventions in IBS patients remain to be elucidated.
Ronnie Fass, MD, is a professor of medicine at Case Western Reserve University, Cleveland, as well as the medical director of the Digestive Health Center and director of the division of gastroenterology and hepatology, head, esophageal and swallowing center at MetroHealth Medical Center, also in Cleveland. He has no conflicts of interest.
Primarily home-based cognitive-behavioral therapy improved irritable bowel syndrome symptoms at least as much as conventional CBT, cut clinician time by 60%, and significantly outperformed educational sessions in a multicenter clinical trial reported in the July issue of Gastroenterology.
Acutely, primarily home-based CBT produced a mean 61% improvement in self-reported symptoms on the IBS version of the Clinical Global Impressions Scale, versus 44% for the educational control group (P less than .05), wrote Jeffrey M. Lackner, PsyD, of the State University of New York at Buffalo and his associates. Blinded gastroenterologists reported improvements of 56% and 40%, respectively (P less than .05). The superiority of the minimal-contact CBT program held up at 6 months and equivalence tests found it “at least as effective as standard CBT,” the researchers wrote.
IBS is a major area of unmet clinical need that costs the United States some $28 billion annually. Clinicians and patients lack both reliable biomarkers and “uniformly effective” therapies, the investigators noted. In recent years, severe adverse events have greatly restricted the availability of otherwise promising Food and Drug Administration–approved therapies, such as Lotronex (alosetron hydrochlorine), which has been linked to ischemic colitis and fatal cases of ruptured bowel, and Zelnorm (tegaserod maleate), which has been associated with myocardial infarction, stroke, and unstable angina.
In contrast, face-to-face CBT is safe, efficacious, and guideline recommended for IBS. However, uptake is limited by cost, stigma, geography, and a shortage of certified providers, the researchers noted. They enrolled 436 patients with IBS based on Rome III criteria and randomly assigned them to one of three interventions. The standard CBT group received 10 weekly, 60-minute, face-to-face CBT sessions on brain-gut interactions, symptom triggers and monitoring, muscle relaxation, worry control, problem-solving, and relapse prevention. The primarily home-based CBT group covered the same topics but attended only four clinic sessions and was provided home study materials. Finally, the education group attended four sessions with background information on IBS and the role of stress, diet, and exercise.
Baseline characteristics were comparable among groups, as were dropout rates (9% overall). In all, 89% of patients completed at least 8 of 10 standard cognitive-behavioral therapy sessions or at least three of four home-based CBT or educational sessions. Six months after the interventions ended, primarily home-based CBT continued to outperform education (blinded gastroenterologist-reported improvements, 58.4% and 44.8%, respectively; P = .05 for difference between groups).
Equivalence tests indicated that the minimal-CBT intervention was at least as effective as standard CBT, and improvements were not primarily the result of concomitant medications, according to the researchers. Nonetheless, only 42% of patients who benefited from CBT achieved remission, defined as no or mild IBS symptoms on the gastroenterologist-administered Clinical Global Impressions Scale. Unremitted patients might benefit from combining CBT with medical therapies that target both “central and peripheral mechanisms of IBS,” the investigators said.
The three interventions produced comparable acute and longer-term improvements on the IBS Symptom Severity Scale, which emphasizes sensory symptoms and therefore might be a less sensitive endpoint than the Clinical Global Impressions Scale, the researchers noted. Nonetheless, CBT produced some of the strongest absolute symptomatic improvements ever reported for IBS. “To put these data in context, treatment response of FDA-approved pharmacological agents using global IBS symptom improvement scales range from 17% to 40%,” the researchers wrote.
The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
SOURCE: Lackner JM et al. Gastroenterology. 2018 Apr 24. doi: 10.1053/j.gastro.2018.03.063.
Primarily home-based cognitive-behavioral therapy improved irritable bowel syndrome symptoms at least as much as conventional CBT, cut clinician time by 60%, and significantly outperformed educational sessions in a multicenter clinical trial reported in the July issue of Gastroenterology.
Acutely, primarily home-based CBT produced a mean 61% improvement in self-reported symptoms on the IBS version of the Clinical Global Impressions Scale, versus 44% for the educational control group (P less than .05), wrote Jeffrey M. Lackner, PsyD, of the State University of New York at Buffalo and his associates. Blinded gastroenterologists reported improvements of 56% and 40%, respectively (P less than .05). The superiority of the minimal-contact CBT program held up at 6 months and equivalence tests found it “at least as effective as standard CBT,” the researchers wrote.
IBS is a major area of unmet clinical need that costs the United States some $28 billion annually. Clinicians and patients lack both reliable biomarkers and “uniformly effective” therapies, the investigators noted. In recent years, severe adverse events have greatly restricted the availability of otherwise promising Food and Drug Administration–approved therapies, such as Lotronex (alosetron hydrochlorine), which has been linked to ischemic colitis and fatal cases of ruptured bowel, and Zelnorm (tegaserod maleate), which has been associated with myocardial infarction, stroke, and unstable angina.
In contrast, face-to-face CBT is safe, efficacious, and guideline recommended for IBS. However, uptake is limited by cost, stigma, geography, and a shortage of certified providers, the researchers noted. They enrolled 436 patients with IBS based on Rome III criteria and randomly assigned them to one of three interventions. The standard CBT group received 10 weekly, 60-minute, face-to-face CBT sessions on brain-gut interactions, symptom triggers and monitoring, muscle relaxation, worry control, problem-solving, and relapse prevention. The primarily home-based CBT group covered the same topics but attended only four clinic sessions and was provided home study materials. Finally, the education group attended four sessions with background information on IBS and the role of stress, diet, and exercise.
Baseline characteristics were comparable among groups, as were dropout rates (9% overall). In all, 89% of patients completed at least 8 of 10 standard cognitive-behavioral therapy sessions or at least three of four home-based CBT or educational sessions. Six months after the interventions ended, primarily home-based CBT continued to outperform education (blinded gastroenterologist-reported improvements, 58.4% and 44.8%, respectively; P = .05 for difference between groups).
Equivalence tests indicated that the minimal-CBT intervention was at least as effective as standard CBT, and improvements were not primarily the result of concomitant medications, according to the researchers. Nonetheless, only 42% of patients who benefited from CBT achieved remission, defined as no or mild IBS symptoms on the gastroenterologist-administered Clinical Global Impressions Scale. Unremitted patients might benefit from combining CBT with medical therapies that target both “central and peripheral mechanisms of IBS,” the investigators said.
The three interventions produced comparable acute and longer-term improvements on the IBS Symptom Severity Scale, which emphasizes sensory symptoms and therefore might be a less sensitive endpoint than the Clinical Global Impressions Scale, the researchers noted. Nonetheless, CBT produced some of the strongest absolute symptomatic improvements ever reported for IBS. “To put these data in context, treatment response of FDA-approved pharmacological agents using global IBS symptom improvement scales range from 17% to 40%,” the researchers wrote.
The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.
SOURCE: Lackner JM et al. Gastroenterology. 2018 Apr 24. doi: 10.1053/j.gastro.2018.03.063.
FROM GASTROENTEROLOGY
Key clinical point: Primarily home-based CBT significantly reduced self-reported and gastroenterologist-assessed symptoms of IBS.
Major finding: The intervention required 60% less clinician time and was at least as effective as 10 sessions of conventional CBT, according to responses to the Clinical Global Impressions Improvement Scale. CBT also significantly outperformed the education control (P less than .05).
Study details: Two-center, single-blinded randomized trial of 436 patients with IBS per Rome III criteria.
Disclosures: The National Institutes of Health provided funding. The researchers reported having no conflicts of interest.
Source: Lackner JM et al. Gastroenterology. 2018 Apr 24. doi: 10.1053/j.gastro.2018.03.063.
Barrett’s esophagus risk factor profile may predict progression
Older age, male sex, smoking, longer segment length, and low-grade dysplasia were significant risk factors for progression of Barrett’s esophagus in a meta-analysis of 20 studies.
“Individuals with these features should undergo more intensive surveillance or endoscopic therapy,” Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., and his associates wrote in Clinical Gastroenterology and Hepatology. “Smoking is a modifiable risk factor for cancer prevention in patients with BE.”
“Currently, gastrointestinal societies’ guidelines on BE surveillance are solely based on dysplasia grade and do not take into account any of the other risk factors,” the reviewers concluded. Their findings could form the backbone of a risk score that identifies high-risk BE patients with baseline low-grade dysplasia or nondysplastic BE “who would benefit from intensive surveillance or endoscopic therapy.”
Esophageal adenocarcinoma is on the rise and fewer than one in five patients survive 5 years past diagnosis. Endoscopic surveillance for esophageal adenocarcinoma is recommended in Barrett’s esophagus, but only about one in 10 esophageal adenocarcinoma patients has a preceding BE diagnosis. “This ostensible discrepancy has raised concerns about the effectiveness of current screening and surveillance programs,” the reviewers noted. Studies also have yielded conflicting evidence about the value of endoscopic surveillance as currently performed. To help prioritize BE patients for surveillance, the reviewers searched EMBASE, MEDLINE, and Web of Science from inception through May 2016 for cohort studies of risk factors for progression of BE among patients with either no dysplasia or low-grade dysplasia.
The 20 studies covered 1,231 BE progression events among 74,943 patients. In separate pooled estimates, progression of BE correlated significantly with older age (odds ratio, 1.03; 95% CI, 1.01–1.05), male sex (OR, 2.2; 95% CI, 1.8-2.5), current or former smoking (OR, 1.5; 95% CI, 1.09-2.0), and greater BE segment length (OR, 1.3; 95% CI, 1.16-1.36). Results tended to be homogeneous among studies, said the reviewers. Low-grade dysplasia correlated strongly with progression (OR, 4.3; 95% CI, 2.6-7.0), while use of proton pump inhibitors (OR, 0.55; 95% CI, 0.32–0.96) and statins (OR, 0.48; 95% CI, 0.31-0.73) showed the opposite trend. “Alcohol use and obesity did not associate with risk of progression,” the reviewers added.
Thirteen studies in the meta-analysis were from Europe, six were from the United States, and one was from Australia. Ten were multicenter studies, 13 were deemed high-quality, three were deemed medium-quality, and four were deemed low-quality. The reviewers were unable to assess dose-response relationships for relevant factors, such as alcohol, tobacco, and medications, and not all studies accounted for potential confounding.
Only four studies included multivariate analyses to control for the confounding effects of age, sex, and BE characteristics (length and dysplasia). When the reviewers analyzed only these studies, older age and smoking no longer predicted BE progression. Use of proton pump inhibitors remained protective, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) became protective, while statin use lost significance.
The reviewers disclosed no external funding sources or conflicts of interest.
SOURCE: Krishnamoorthi R, et al. Clinical Gastroenterol and Hepatol. 2017 Nov 30. doi: 10.1016/j.cgh.2017.11.044
Endoscopic surveillance is currently recommended for nondysplastic Barrett's esophagus (BE), but there are conflicting results on the effectiveness of surveillance on esophageal adenocarcinoma outcomes. This meta-analysis by Krishnamoorthi et al. found several risk factors associated with BE progression (i.e., age, male sex, smoking, BE length) among patients with nondysplastic BE or low-grade dysplasia. Current recommendations for BE surveillance intervals are solely based on dysplasia grade without consideration for other high-risk features (i.e., smoking, BE length, age). This meta-analysis demonstrates that some patients with nondysplastic BE are at a higher risk of neoplastic progression, and the AGA recommendation for BE surveillance every 3-5 years may not be suitable for all.
IMG: 2400A107.SIG Tan_Mimi_TEXAS_web
Parasa et al. recently developed a risk prediction model to stratify risk of progression in patients with nondysplastic BE based on BE length, male sex, smoking, and baseline low-grade dysplasia. Patients with one or more of these risk factors are at highest risk of neoplastic progression and may benefit from shorter surveillance intervals or endoscopic eradication therapy.
Mimi C. Tan, MD, MPH, is a postdoctoral fellow in gastroenterology and hepatology, T32 research track at Baylor College of Medicine, Houston, and an investigator at the Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center, Houston. She has no conflicts.
Endoscopic surveillance is currently recommended for nondysplastic Barrett's esophagus (BE), but there are conflicting results on the effectiveness of surveillance on esophageal adenocarcinoma outcomes. This meta-analysis by Krishnamoorthi et al. found several risk factors associated with BE progression (i.e., age, male sex, smoking, BE length) among patients with nondysplastic BE or low-grade dysplasia. Current recommendations for BE surveillance intervals are solely based on dysplasia grade without consideration for other high-risk features (i.e., smoking, BE length, age). This meta-analysis demonstrates that some patients with nondysplastic BE are at a higher risk of neoplastic progression, and the AGA recommendation for BE surveillance every 3-5 years may not be suitable for all.
IMG: 2400A107.SIG Tan_Mimi_TEXAS_web
Parasa et al. recently developed a risk prediction model to stratify risk of progression in patients with nondysplastic BE based on BE length, male sex, smoking, and baseline low-grade dysplasia. Patients with one or more of these risk factors are at highest risk of neoplastic progression and may benefit from shorter surveillance intervals or endoscopic eradication therapy.
Mimi C. Tan, MD, MPH, is a postdoctoral fellow in gastroenterology and hepatology, T32 research track at Baylor College of Medicine, Houston, and an investigator at the Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center, Houston. She has no conflicts.
Endoscopic surveillance is currently recommended for nondysplastic Barrett's esophagus (BE), but there are conflicting results on the effectiveness of surveillance on esophageal adenocarcinoma outcomes. This meta-analysis by Krishnamoorthi et al. found several risk factors associated with BE progression (i.e., age, male sex, smoking, BE length) among patients with nondysplastic BE or low-grade dysplasia. Current recommendations for BE surveillance intervals are solely based on dysplasia grade without consideration for other high-risk features (i.e., smoking, BE length, age). This meta-analysis demonstrates that some patients with nondysplastic BE are at a higher risk of neoplastic progression, and the AGA recommendation for BE surveillance every 3-5 years may not be suitable for all.
IMG: 2400A107.SIG Tan_Mimi_TEXAS_web
Parasa et al. recently developed a risk prediction model to stratify risk of progression in patients with nondysplastic BE based on BE length, male sex, smoking, and baseline low-grade dysplasia. Patients with one or more of these risk factors are at highest risk of neoplastic progression and may benefit from shorter surveillance intervals or endoscopic eradication therapy.
Mimi C. Tan, MD, MPH, is a postdoctoral fellow in gastroenterology and hepatology, T32 research track at Baylor College of Medicine, Houston, and an investigator at the Center for Innovations in Quality, Effectiveness, and Safety at the Michael E. DeBakey VA Medical Center, Houston. She has no conflicts.
Older age, male sex, smoking, longer segment length, and low-grade dysplasia were significant risk factors for progression of Barrett’s esophagus in a meta-analysis of 20 studies.
“Individuals with these features should undergo more intensive surveillance or endoscopic therapy,” Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., and his associates wrote in Clinical Gastroenterology and Hepatology. “Smoking is a modifiable risk factor for cancer prevention in patients with BE.”
“Currently, gastrointestinal societies’ guidelines on BE surveillance are solely based on dysplasia grade and do not take into account any of the other risk factors,” the reviewers concluded. Their findings could form the backbone of a risk score that identifies high-risk BE patients with baseline low-grade dysplasia or nondysplastic BE “who would benefit from intensive surveillance or endoscopic therapy.”
Esophageal adenocarcinoma is on the rise and fewer than one in five patients survive 5 years past diagnosis. Endoscopic surveillance for esophageal adenocarcinoma is recommended in Barrett’s esophagus, but only about one in 10 esophageal adenocarcinoma patients has a preceding BE diagnosis. “This ostensible discrepancy has raised concerns about the effectiveness of current screening and surveillance programs,” the reviewers noted. Studies also have yielded conflicting evidence about the value of endoscopic surveillance as currently performed. To help prioritize BE patients for surveillance, the reviewers searched EMBASE, MEDLINE, and Web of Science from inception through May 2016 for cohort studies of risk factors for progression of BE among patients with either no dysplasia or low-grade dysplasia.
The 20 studies covered 1,231 BE progression events among 74,943 patients. In separate pooled estimates, progression of BE correlated significantly with older age (odds ratio, 1.03; 95% CI, 1.01–1.05), male sex (OR, 2.2; 95% CI, 1.8-2.5), current or former smoking (OR, 1.5; 95% CI, 1.09-2.0), and greater BE segment length (OR, 1.3; 95% CI, 1.16-1.36). Results tended to be homogeneous among studies, said the reviewers. Low-grade dysplasia correlated strongly with progression (OR, 4.3; 95% CI, 2.6-7.0), while use of proton pump inhibitors (OR, 0.55; 95% CI, 0.32–0.96) and statins (OR, 0.48; 95% CI, 0.31-0.73) showed the opposite trend. “Alcohol use and obesity did not associate with risk of progression,” the reviewers added.
Thirteen studies in the meta-analysis were from Europe, six were from the United States, and one was from Australia. Ten were multicenter studies, 13 were deemed high-quality, three were deemed medium-quality, and four were deemed low-quality. The reviewers were unable to assess dose-response relationships for relevant factors, such as alcohol, tobacco, and medications, and not all studies accounted for potential confounding.
Only four studies included multivariate analyses to control for the confounding effects of age, sex, and BE characteristics (length and dysplasia). When the reviewers analyzed only these studies, older age and smoking no longer predicted BE progression. Use of proton pump inhibitors remained protective, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) became protective, while statin use lost significance.
The reviewers disclosed no external funding sources or conflicts of interest.
SOURCE: Krishnamoorthi R, et al. Clinical Gastroenterol and Hepatol. 2017 Nov 30. doi: 10.1016/j.cgh.2017.11.044
Older age, male sex, smoking, longer segment length, and low-grade dysplasia were significant risk factors for progression of Barrett’s esophagus in a meta-analysis of 20 studies.
“Individuals with these features should undergo more intensive surveillance or endoscopic therapy,” Rajesh Krishnamoorthi, MD, of Mayo Clinic in Rochester, Minn., and his associates wrote in Clinical Gastroenterology and Hepatology. “Smoking is a modifiable risk factor for cancer prevention in patients with BE.”
“Currently, gastrointestinal societies’ guidelines on BE surveillance are solely based on dysplasia grade and do not take into account any of the other risk factors,” the reviewers concluded. Their findings could form the backbone of a risk score that identifies high-risk BE patients with baseline low-grade dysplasia or nondysplastic BE “who would benefit from intensive surveillance or endoscopic therapy.”
Esophageal adenocarcinoma is on the rise and fewer than one in five patients survive 5 years past diagnosis. Endoscopic surveillance for esophageal adenocarcinoma is recommended in Barrett’s esophagus, but only about one in 10 esophageal adenocarcinoma patients has a preceding BE diagnosis. “This ostensible discrepancy has raised concerns about the effectiveness of current screening and surveillance programs,” the reviewers noted. Studies also have yielded conflicting evidence about the value of endoscopic surveillance as currently performed. To help prioritize BE patients for surveillance, the reviewers searched EMBASE, MEDLINE, and Web of Science from inception through May 2016 for cohort studies of risk factors for progression of BE among patients with either no dysplasia or low-grade dysplasia.
The 20 studies covered 1,231 BE progression events among 74,943 patients. In separate pooled estimates, progression of BE correlated significantly with older age (odds ratio, 1.03; 95% CI, 1.01–1.05), male sex (OR, 2.2; 95% CI, 1.8-2.5), current or former smoking (OR, 1.5; 95% CI, 1.09-2.0), and greater BE segment length (OR, 1.3; 95% CI, 1.16-1.36). Results tended to be homogeneous among studies, said the reviewers. Low-grade dysplasia correlated strongly with progression (OR, 4.3; 95% CI, 2.6-7.0), while use of proton pump inhibitors (OR, 0.55; 95% CI, 0.32–0.96) and statins (OR, 0.48; 95% CI, 0.31-0.73) showed the opposite trend. “Alcohol use and obesity did not associate with risk of progression,” the reviewers added.
Thirteen studies in the meta-analysis were from Europe, six were from the United States, and one was from Australia. Ten were multicenter studies, 13 were deemed high-quality, three were deemed medium-quality, and four were deemed low-quality. The reviewers were unable to assess dose-response relationships for relevant factors, such as alcohol, tobacco, and medications, and not all studies accounted for potential confounding.
Only four studies included multivariate analyses to control for the confounding effects of age, sex, and BE characteristics (length and dysplasia). When the reviewers analyzed only these studies, older age and smoking no longer predicted BE progression. Use of proton pump inhibitors remained protective, and use of nonsteroidal anti-inflammatory drugs (NSAIDs) became protective, while statin use lost significance.
The reviewers disclosed no external funding sources or conflicts of interest.
SOURCE: Krishnamoorthi R, et al. Clinical Gastroenterol and Hepatol. 2017 Nov 30. doi: 10.1016/j.cgh.2017.11.044
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Male sex, older age, smoking, greater segment length, and low-grade dysplasia separately predicted progression of Barrett’s esophagus.
Major finding: Pooled odds ratios for risk ranged from 4.3 (low-grade dysplasia) to 1.03 (older age).
Study details: Systematic review and meta-analysis of 20 studies published through May 2016.
Disclosures: The reviewers disclosed no external funding sources or conflicts of interest.
Source: Krishnamoorthi R, et al. Clinical Gastroenterol and Hepatol. 2017 Nov 30.
Fecal calprotectin levels predicted mucosal, deep healing in pediatric Crohn’s
For children with Crohn’s disease, fecal calprotectin levels below 300 mcg indicated mucosal healing, while values below 100 mcg signified deep healing in a multicenter, 151-patient study.
Sensitivity was 80% for mucosal healing and 71% for deep healing, while specificities were 81% and 92%, respectively, said Inbar Nakar of the Hebrew University of Jerusalem, with her associates. In line with prior studies, adding C-reactive protein (CRP) to fecal calprotectin improved neither sensitivity or specificity, the researchers wrote in Clinical Gastroenterology and Hepatology.
Bowel healing is a crucial goal in Crohn’s disease (CD). Because pediatric transmural healing had not been studied, the researchers analyzed data from the ImageKids study, a multicenter effort to develop magnetic resonance enterography (MRE) measures for CD patients aged 6-18 years. Participants averaged 14 years old with a standard deviation of 2 years. Assessments included MRE, complete ileocolonoscopic evaluation, CRP, and fecal calprotectin. The researchers defined mucosal healing as a Simple Endoscopic Severity Index in Crohn’s Disease score below 3, transmural healing as an MRE visual analog score below 20 mm, and deep healing as transmural plus mucosal healing.
Nearly one-third of patients had healing only in the mucosa or the bowel wall, but not both; 6% had mucosal healing but transmural inflammation, and 25% of children had transmural healing but mucosal inflammation. In addition, 14% of children had deep healing, and 55% of children had both mucosal and transmural inflammation. Those findings highlight “the discrepancy between mucosal and transmural inflammation and the importance of evaluating the disease by both ileocolonoscopy and imaging,” the researchers wrote.
Median calprotectin levels varied significantly by healing status (P less than .001). They were lowest (10 mcg/g) for deep healing, followed by either transmural or mucosal inflammation, and were highest (median, 810 mcg/g) when children had both mucosal and transmural inflammation. Calprotectin in children with deep healing had an area under the receiver operating characteristic curve value of 0.93 (95% confidence interval, 0.89- 0.98). In contrast, CRP level identified children with deep healing with an AUROC value of only 0.81 (95% CI, 0.71-0.90).
Although “calprotectin level is driven primarily by mucosal healing, [it] is still superior to CRP,” the investigators concluded. “Although a calprotectin cutoff [less than] 300 mcg/g predicted mucosal healing, a lower cutoff of [less than] 100 mcg/g may be more suitable to predict deep healing.” However, they emphasized that fecal calprotectin level is only moderately accurate in predicting mucosal or transmural healing in children with CD. They advised physicians to “be familiar with the predictive values of each cutoff before incorporating them in clinical decision making.”
An educational grant from AbbVie funded the ImageKids study. AbbVie was not otherwise involved in the study. Two coinvestigators disclosed ties to AbbVie and other pharmaceutical companies. There were no other disclosures.
SOURCE: Nakar I et al. Clin Gastroenterol Hepatol. 2018 Mar 2. doi: 10.1016/j.cgh.2018.01.024.
For children with Crohn’s disease, fecal calprotectin levels below 300 mcg indicated mucosal healing, while values below 100 mcg signified deep healing in a multicenter, 151-patient study.
Sensitivity was 80% for mucosal healing and 71% for deep healing, while specificities were 81% and 92%, respectively, said Inbar Nakar of the Hebrew University of Jerusalem, with her associates. In line with prior studies, adding C-reactive protein (CRP) to fecal calprotectin improved neither sensitivity or specificity, the researchers wrote in Clinical Gastroenterology and Hepatology.
Bowel healing is a crucial goal in Crohn’s disease (CD). Because pediatric transmural healing had not been studied, the researchers analyzed data from the ImageKids study, a multicenter effort to develop magnetic resonance enterography (MRE) measures for CD patients aged 6-18 years. Participants averaged 14 years old with a standard deviation of 2 years. Assessments included MRE, complete ileocolonoscopic evaluation, CRP, and fecal calprotectin. The researchers defined mucosal healing as a Simple Endoscopic Severity Index in Crohn’s Disease score below 3, transmural healing as an MRE visual analog score below 20 mm, and deep healing as transmural plus mucosal healing.
Nearly one-third of patients had healing only in the mucosa or the bowel wall, but not both; 6% had mucosal healing but transmural inflammation, and 25% of children had transmural healing but mucosal inflammation. In addition, 14% of children had deep healing, and 55% of children had both mucosal and transmural inflammation. Those findings highlight “the discrepancy between mucosal and transmural inflammation and the importance of evaluating the disease by both ileocolonoscopy and imaging,” the researchers wrote.
Median calprotectin levels varied significantly by healing status (P less than .001). They were lowest (10 mcg/g) for deep healing, followed by either transmural or mucosal inflammation, and were highest (median, 810 mcg/g) when children had both mucosal and transmural inflammation. Calprotectin in children with deep healing had an area under the receiver operating characteristic curve value of 0.93 (95% confidence interval, 0.89- 0.98). In contrast, CRP level identified children with deep healing with an AUROC value of only 0.81 (95% CI, 0.71-0.90).
Although “calprotectin level is driven primarily by mucosal healing, [it] is still superior to CRP,” the investigators concluded. “Although a calprotectin cutoff [less than] 300 mcg/g predicted mucosal healing, a lower cutoff of [less than] 100 mcg/g may be more suitable to predict deep healing.” However, they emphasized that fecal calprotectin level is only moderately accurate in predicting mucosal or transmural healing in children with CD. They advised physicians to “be familiar with the predictive values of each cutoff before incorporating them in clinical decision making.”
An educational grant from AbbVie funded the ImageKids study. AbbVie was not otherwise involved in the study. Two coinvestigators disclosed ties to AbbVie and other pharmaceutical companies. There were no other disclosures.
SOURCE: Nakar I et al. Clin Gastroenterol Hepatol. 2018 Mar 2. doi: 10.1016/j.cgh.2018.01.024.
For children with Crohn’s disease, fecal calprotectin levels below 300 mcg indicated mucosal healing, while values below 100 mcg signified deep healing in a multicenter, 151-patient study.
Sensitivity was 80% for mucosal healing and 71% for deep healing, while specificities were 81% and 92%, respectively, said Inbar Nakar of the Hebrew University of Jerusalem, with her associates. In line with prior studies, adding C-reactive protein (CRP) to fecal calprotectin improved neither sensitivity or specificity, the researchers wrote in Clinical Gastroenterology and Hepatology.
Bowel healing is a crucial goal in Crohn’s disease (CD). Because pediatric transmural healing had not been studied, the researchers analyzed data from the ImageKids study, a multicenter effort to develop magnetic resonance enterography (MRE) measures for CD patients aged 6-18 years. Participants averaged 14 years old with a standard deviation of 2 years. Assessments included MRE, complete ileocolonoscopic evaluation, CRP, and fecal calprotectin. The researchers defined mucosal healing as a Simple Endoscopic Severity Index in Crohn’s Disease score below 3, transmural healing as an MRE visual analog score below 20 mm, and deep healing as transmural plus mucosal healing.
Nearly one-third of patients had healing only in the mucosa or the bowel wall, but not both; 6% had mucosal healing but transmural inflammation, and 25% of children had transmural healing but mucosal inflammation. In addition, 14% of children had deep healing, and 55% of children had both mucosal and transmural inflammation. Those findings highlight “the discrepancy between mucosal and transmural inflammation and the importance of evaluating the disease by both ileocolonoscopy and imaging,” the researchers wrote.
Median calprotectin levels varied significantly by healing status (P less than .001). They were lowest (10 mcg/g) for deep healing, followed by either transmural or mucosal inflammation, and were highest (median, 810 mcg/g) when children had both mucosal and transmural inflammation. Calprotectin in children with deep healing had an area under the receiver operating characteristic curve value of 0.93 (95% confidence interval, 0.89- 0.98). In contrast, CRP level identified children with deep healing with an AUROC value of only 0.81 (95% CI, 0.71-0.90).
Although “calprotectin level is driven primarily by mucosal healing, [it] is still superior to CRP,” the investigators concluded. “Although a calprotectin cutoff [less than] 300 mcg/g predicted mucosal healing, a lower cutoff of [less than] 100 mcg/g may be more suitable to predict deep healing.” However, they emphasized that fecal calprotectin level is only moderately accurate in predicting mucosal or transmural healing in children with CD. They advised physicians to “be familiar with the predictive values of each cutoff before incorporating them in clinical decision making.”
An educational grant from AbbVie funded the ImageKids study. AbbVie was not otherwise involved in the study. Two coinvestigators disclosed ties to AbbVie and other pharmaceutical companies. There were no other disclosures.
SOURCE: Nakar I et al. Clin Gastroenterol Hepatol. 2018 Mar 2. doi: 10.1016/j.cgh.2018.01.024.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Fecal calprotectin levels below 300 mcg indicated mucosal healing, while values below 100 mcg signified deep healing in children with Crohn’s disease.
Major finding: Sensitivity was 80% for mucosal healing and 71% for deep healing, while specificities were 81% and 92%, respectively.
Study details: A multicenter study of 151 patients aged 6-18 years with Crohn’s disease.
Disclosures: AbbVie funded the ImageKids study through an educational grant but otherwise was not involved in the study. Two coinvestigators disclosed ties to AbbVie and other pharmaceutical companies. There were no other disclosures.
Source: Nakar I et al. Clin Gastroenterol Hepatol. 2018 Mar 2. doi: 10.1016/j.cgh.2018.01.024.