From the Journals

As the science of Crohn’s disease (CD) rapidly evolves, AGA has issued a living guideline on the pharmacologic management of moderately to severely active CD.

The guideline was published in Gastroenterology by an expert panel chaired by Frank I. Scott, MD, MSCE, a gastroenterologist at the Crohn’s and Colitis Center in the Division of Gastroenterology and Hepatology at the University of Colorado Anschutz School of Medicine in Aurora, Colorado.

It makes 16 main recommendations in a comprehensive, patient-centered, evidence-based approach to utilizing an array of medical options endorsing early use of advanced therapies such as biologics. Of these, one is a strong recommendation, nine are conditional recommendations, and six are identified as knowledge gaps.

“There’s been a significant increase in the number of therapies available for clinicians and patients when considering treatment options for moderate-to-severe [CD] since the prior guidelines in 2021,” Scott told GI & Hepatology News. “We hope these guidelines will help clinicians determine how to maximize the potential benefit of the full armamentarium of therapies available to treat this disease.”

Guideline co-author Siddharth Singh, MD, MS, of the Division of Gastroenterology and Hepatology at the Mayo Clinic Arizona in Scottsdale, Arizona, said the goal of the guideline is to translate evidence into clear, meaningful recommendations for frontline clinicians. “It’s patient centered but also provider centric. We want to help physicians and advanced practice providers make timely, actionable decisions for their patients.”

Among the recommendations:

• Early initiation of high-efficacy advanced therapy to prevent progression is recommended over insurance-driven step therapy.
• For adult patients naive to advanced therapies, the AGA recommends infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib over no treatment and suggests the use of certolizumab pegol or vedolizumab over no treatment.
• For adults naive to advanced therapies, the AGA suggests using a higher-efficacy medication (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, or guselkumab) rather than a lower-efficacy option (certolizumab pegol or upadacitinib).
• For those previously exposed to one or more advanced therapies, the AGA suggests a higher-efficacy medication (adalimumab, risankizumab, guselkumab, or upadacitinib) or an intermediate-efficacy medication (ustekinumab or mirikizumab) rather than a lower-efficacy medication (vedolizumab or certolizumab pegol).
• For adult outpatients, the AGA suggests against thiopurine monotherapy for induction of remission but suggests thiopurine monotherapy over no treatment for maintenance of (typically corticosteroid-induced) remission.
• The guideline favors subcutaneous methotrexate for induction and maintenance of remission but suggests against oral methotrexate.
• Combination therapy with infliximab and thiopurines is suggested over infliximab monotherapy, particularly in those naive to thiopurines.

“We identified several critical knowledge gaps, including the role of combination therapy for non-[TNF] biologics, as well as whether targeting endoscopic remission as opposed to clinical remission yields additional benefit,” Scott said.

Most of the panel’s time was spent considering evidence and recommendations in relation to how therapies should be positioned among each other in light of patients’ treatment history. “For those who were advanced therapy-naive, we used two groups, or ‘buckets’: higher and lower efficacy,” Scott said. “For advanced therapy-exposed individuals, we used higher, intermediate, and lower buckets, recommending the use of higher- or intermediate-efficacy medications.” Network meta-analyses were done to determine which therapies belong in which categories.

Perhaps the most unexpected outcome from the panel’s review was the inability to make a recommendation on treating to a target of mucosal healing. “This target conceptually makes sense, but prospective clinical trial data supporting this approach over targeting clinical remission unfortunately are currently limited,” Scott said. Several ongoing clinical trials are assessing this endpoint. “We hope future versions of these guidelines can make a formal recommendation regarding targeting mucosal healing. The benefit of our living guideline approach is that as these data become available, we will be able incorporate them more rapidly.”

Offering a nonparticipant’s perspective on the living, updatable guideline, Ahmed Hassan Gemei, MD, a gastroenterologist at Northwell North Shore University Hospital in Manhasset, New York, said the update was needed because of the shifting therapeutic landscape.

“As great as that is for patient care, it can be daunting for gastroenterologists to keep up with the onslaught of evidence and growing repertoire of advanced therapies,” he told GI & Hepatology News. “For a rapidly evolving field like inflammatory bowel disease, having a guideline come out once every 3-5 years can lag behind the evidence significantly. There is something special and much needed about a living guideline that gets regularly updated as newer data come out, which we have come to appreciate with the AGA living guidelines for ulcerative colitis.”

As to facilitating clinical decision-making, Gemei added, “It does a great job at summarizing the available evidence, making life easier for gastroenterologists who are trying to make evidence-based decisions for their patients. But having a straightforward algorithmic approach to the management of [CD] is ultimately limited by patient-specific differences and patient and payor preferences, as well as gaps in the data such as comparative effectiveness, sequencing of therapy, and advanced dual therapies.”

When it comes to choosing a drug, for example, gastroenterologists are given a general overview of which ones have higher or lower efficacy, but the choice depends on multiple factors, including CD phenotype, previous medications, and patient preference with regard to relative safety, as well as payor preference (although clinicians often try to influence this).

The guidelines align broadly but with some differences with other societal guidelines in the US and Europe. But, said Gemei, the absence of a recommendation for or against treating to a target of endoscopic healing was surprising. “This has been standard practice in recent years based on the updated STRIDE [Selecting Therapeutic Targets in Inflammatory Bowel Disease] consensus statements, as well as recent American College of Gastroenterology guidelines. Though I understand the reason behind this decision, which was simply lack of strong data, it’s still a departure from other society recommendations and current practice. I doubt this will change how we manage our patient, though, and luckily, this is a living guideline, so as more data come out, we should see an update in this area.”

He noted that despite this and other guidelines recommending against the use of 5-aminosalicylic acids in CD, “we still see many of our colleagues using it for their [CD] patients. Hopefully, this guideline can be a helpful resource for everyone trying to update their practice.”

Gemei agreed with the authors that there are persistent knowledge gaps, including insufficient data from head-to-head effectiveness studies, optimal biologic sequencing after failure, advanced combination therapy (such as JAK inhibitors plus anti-interleukin-23), radiologic and endoscopic disease monitoring intervals, and therapy withdrawal strategies after long-term remission. “So there’s a lot we still need to understand better,” he said. “Until we have more data and guidance, we are still practicing all these things based on the available evidence as well as local practice patterns.”

Overall, said Scott, the guidance highlights the options with the best supporting evidence while incorporating the patient’s prior treatment journey. “It’s also important to emphasize that treatment decisions should be individualized and should involve shared decision-making among providers and their patients,” he added. “Patient preferences, age, active comorbidities, and pregnancy should always be considered when selecting the appropriate treatment plan.”

All funding for this guidance was supplied by AGA. The guideline chairs had no conflicts of interest, and fewer than 50% of guideline panel members had conflicts of interest. Gemei had no conflicts of interest.

A version of this article appeared on Medscape.com.

As the science of Crohn’s disease (CD) rapidly evolves, AGA has issued a living guideline on the pharmacologic management of moderately to severely active CD.

The guideline was published in Gastroenterology by an expert panel chaired by Frank I. Scott, MD, MSCE, a gastroenterologist at the Crohn’s and Colitis Center in the Division of Gastroenterology and Hepatology at the University of Colorado Anschutz School of Medicine in Aurora, Colorado.

It makes 16 main recommendations in a comprehensive, patient-centered, evidence-based approach to utilizing an array of medical options endorsing early use of advanced therapies such as biologics. Of these, one is a strong recommendation, nine are conditional recommendations, and six are identified as knowledge gaps.

“There’s been a significant increase in the number of therapies available for clinicians and patients when considering treatment options for moderate-to-severe [CD] since the prior guidelines in 2021,” Scott told GI & Hepatology News. “We hope these guidelines will help clinicians determine how to maximize the potential benefit of the full armamentarium of therapies available to treat this disease.”

Guideline co-author Siddharth Singh, MD, MS, of the Division of Gastroenterology and Hepatology at the Mayo Clinic Arizona in Scottsdale, Arizona, said the goal of the guideline is to translate evidence into clear, meaningful recommendations for frontline clinicians. “It’s patient centered but also provider centric. We want to help physicians and advanced practice providers make timely, actionable decisions for their patients.”

Among the recommendations:

• Early initiation of high-efficacy advanced therapy to prevent progression is recommended over insurance-driven step therapy.
• For adult patients naive to advanced therapies, the AGA recommends infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib over no treatment and suggests the use of certolizumab pegol or vedolizumab over no treatment.
• For adults naive to advanced therapies, the AGA suggests using a higher-efficacy medication (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, or guselkumab) rather than a lower-efficacy option (certolizumab pegol or upadacitinib).
• For those previously exposed to one or more advanced therapies, the AGA suggests a higher-efficacy medication (adalimumab, risankizumab, guselkumab, or upadacitinib) or an intermediate-efficacy medication (ustekinumab or mirikizumab) rather than a lower-efficacy medication (vedolizumab or certolizumab pegol).
• For adult outpatients, the AGA suggests against thiopurine monotherapy for induction of remission but suggests thiopurine monotherapy over no treatment for maintenance of (typically corticosteroid-induced) remission.
• The guideline favors subcutaneous methotrexate for induction and maintenance of remission but suggests against oral methotrexate.
• Combination therapy with infliximab and thiopurines is suggested over infliximab monotherapy, particularly in those naive to thiopurines.

“We identified several critical knowledge gaps, including the role of combination therapy for non-[TNF] biologics, as well as whether targeting endoscopic remission as opposed to clinical remission yields additional benefit,” Scott said.

Most of the panel’s time was spent considering evidence and recommendations in relation to how therapies should be positioned among each other in light of patients’ treatment history. “For those who were advanced therapy-naive, we used two groups, or ‘buckets’: higher and lower efficacy,” Scott said. “For advanced therapy-exposed individuals, we used higher, intermediate, and lower buckets, recommending the use of higher- or intermediate-efficacy medications.” Network meta-analyses were done to determine which therapies belong in which categories.

Perhaps the most unexpected outcome from the panel’s review was the inability to make a recommendation on treating to a target of mucosal healing. “This target conceptually makes sense, but prospective clinical trial data supporting this approach over targeting clinical remission unfortunately are currently limited,” Scott said. Several ongoing clinical trials are assessing this endpoint. “We hope future versions of these guidelines can make a formal recommendation regarding targeting mucosal healing. The benefit of our living guideline approach is that as these data become available, we will be able incorporate them more rapidly.”

Offering a nonparticipant’s perspective on the living, updatable guideline, Ahmed Hassan Gemei, MD, a gastroenterologist at Northwell North Shore University Hospital in Manhasset, New York, said the update was needed because of the shifting therapeutic landscape.

“As great as that is for patient care, it can be daunting for gastroenterologists to keep up with the onslaught of evidence and growing repertoire of advanced therapies,” he told GI & Hepatology News. “For a rapidly evolving field like inflammatory bowel disease, having a guideline come out once every 3-5 years can lag behind the evidence significantly. There is something special and much needed about a living guideline that gets regularly updated as newer data come out, which we have come to appreciate with the AGA living guidelines for ulcerative colitis.”

As to facilitating clinical decision-making, Gemei added, “It does a great job at summarizing the available evidence, making life easier for gastroenterologists who are trying to make evidence-based decisions for their patients. But having a straightforward algorithmic approach to the management of [CD] is ultimately limited by patient-specific differences and patient and payor preferences, as well as gaps in the data such as comparative effectiveness, sequencing of therapy, and advanced dual therapies.”

When it comes to choosing a drug, for example, gastroenterologists are given a general overview of which ones have higher or lower efficacy, but the choice depends on multiple factors, including CD phenotype, previous medications, and patient preference with regard to relative safety, as well as payor preference (although clinicians often try to influence this).

The guidelines align broadly but with some differences with other societal guidelines in the US and Europe. But, said Gemei, the absence of a recommendation for or against treating to a target of endoscopic healing was surprising. “This has been standard practice in recent years based on the updated STRIDE [Selecting Therapeutic Targets in Inflammatory Bowel Disease] consensus statements, as well as recent American College of Gastroenterology guidelines. Though I understand the reason behind this decision, which was simply lack of strong data, it’s still a departure from other society recommendations and current practice. I doubt this will change how we manage our patient, though, and luckily, this is a living guideline, so as more data come out, we should see an update in this area.”

He noted that despite this and other guidelines recommending against the use of 5-aminosalicylic acids in CD, “we still see many of our colleagues using it for their [CD] patients. Hopefully, this guideline can be a helpful resource for everyone trying to update their practice.”

Gemei agreed with the authors that there are persistent knowledge gaps, including insufficient data from head-to-head effectiveness studies, optimal biologic sequencing after failure, advanced combination therapy (such as JAK inhibitors plus anti-interleukin-23), radiologic and endoscopic disease monitoring intervals, and therapy withdrawal strategies after long-term remission. “So there’s a lot we still need to understand better,” he said. “Until we have more data and guidance, we are still practicing all these things based on the available evidence as well as local practice patterns.”

Overall, said Scott, the guidance highlights the options with the best supporting evidence while incorporating the patient’s prior treatment journey. “It’s also important to emphasize that treatment decisions should be individualized and should involve shared decision-making among providers and their patients,” he added. “Patient preferences, age, active comorbidities, and pregnancy should always be considered when selecting the appropriate treatment plan.”

All funding for this guidance was supplied by AGA. The guideline chairs had no conflicts of interest, and fewer than 50% of guideline panel members had conflicts of interest. Gemei had no conflicts of interest.

A version of this article appeared on Medscape.com.

As the science of Crohn’s disease (CD) rapidly evolves, AGA has issued a living guideline on the pharmacologic management of moderately to severely active CD.

The guideline was published in Gastroenterology by an expert panel chaired by Frank I. Scott, MD, MSCE, a gastroenterologist at the Crohn’s and Colitis Center in the Division of Gastroenterology and Hepatology at the University of Colorado Anschutz School of Medicine in Aurora, Colorado.

It makes 16 main recommendations in a comprehensive, patient-centered, evidence-based approach to utilizing an array of medical options endorsing early use of advanced therapies such as biologics. Of these, one is a strong recommendation, nine are conditional recommendations, and six are identified as knowledge gaps.

“There’s been a significant increase in the number of therapies available for clinicians and patients when considering treatment options for moderate-to-severe [CD] since the prior guidelines in 2021,” Scott told GI & Hepatology News. “We hope these guidelines will help clinicians determine how to maximize the potential benefit of the full armamentarium of therapies available to treat this disease.”

Guideline co-author Siddharth Singh, MD, MS, of the Division of Gastroenterology and Hepatology at the Mayo Clinic Arizona in Scottsdale, Arizona, said the goal of the guideline is to translate evidence into clear, meaningful recommendations for frontline clinicians. “It’s patient centered but also provider centric. We want to help physicians and advanced practice providers make timely, actionable decisions for their patients.”

Among the recommendations:

• Early initiation of high-efficacy advanced therapy to prevent progression is recommended over insurance-driven step therapy.
• For adult patients naive to advanced therapies, the AGA recommends infliximab, adalimumab, ustekinumab, risankizumab, mirikizumab, guselkumab, or upadacitinib over no treatment and suggests the use of certolizumab pegol or vedolizumab over no treatment.
• For adults naive to advanced therapies, the AGA suggests using a higher-efficacy medication (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, or guselkumab) rather than a lower-efficacy option (certolizumab pegol or upadacitinib).
• For those previously exposed to one or more advanced therapies, the AGA suggests a higher-efficacy medication (adalimumab, risankizumab, guselkumab, or upadacitinib) or an intermediate-efficacy medication (ustekinumab or mirikizumab) rather than a lower-efficacy medication (vedolizumab or certolizumab pegol).
• For adult outpatients, the AGA suggests against thiopurine monotherapy for induction of remission but suggests thiopurine monotherapy over no treatment for maintenance of (typically corticosteroid-induced) remission.
• The guideline favors subcutaneous methotrexate for induction and maintenance of remission but suggests against oral methotrexate.
• Combination therapy with infliximab and thiopurines is suggested over infliximab monotherapy, particularly in those naive to thiopurines.

“We identified several critical knowledge gaps, including the role of combination therapy for non-[TNF] biologics, as well as whether targeting endoscopic remission as opposed to clinical remission yields additional benefit,” Scott said.

Most of the panel’s time was spent considering evidence and recommendations in relation to how therapies should be positioned among each other in light of patients’ treatment history. “For those who were advanced therapy-naive, we used two groups, or ‘buckets’: higher and lower efficacy,” Scott said. “For advanced therapy-exposed individuals, we used higher, intermediate, and lower buckets, recommending the use of higher- or intermediate-efficacy medications.” Network meta-analyses were done to determine which therapies belong in which categories.

Perhaps the most unexpected outcome from the panel’s review was the inability to make a recommendation on treating to a target of mucosal healing. “This target conceptually makes sense, but prospective clinical trial data supporting this approach over targeting clinical remission unfortunately are currently limited,” Scott said. Several ongoing clinical trials are assessing this endpoint. “We hope future versions of these guidelines can make a formal recommendation regarding targeting mucosal healing. The benefit of our living guideline approach is that as these data become available, we will be able incorporate them more rapidly.”

Offering a nonparticipant’s perspective on the living, updatable guideline, Ahmed Hassan Gemei, MD, a gastroenterologist at Northwell North Shore University Hospital in Manhasset, New York, said the update was needed because of the shifting therapeutic landscape.

“As great as that is for patient care, it can be daunting for gastroenterologists to keep up with the onslaught of evidence and growing repertoire of advanced therapies,” he told GI & Hepatology News. “For a rapidly evolving field like inflammatory bowel disease, having a guideline come out once every 3-5 years can lag behind the evidence significantly. There is something special and much needed about a living guideline that gets regularly updated as newer data come out, which we have come to appreciate with the AGA living guidelines for ulcerative colitis.”

As to facilitating clinical decision-making, Gemei added, “It does a great job at summarizing the available evidence, making life easier for gastroenterologists who are trying to make evidence-based decisions for their patients. But having a straightforward algorithmic approach to the management of [CD] is ultimately limited by patient-specific differences and patient and payor preferences, as well as gaps in the data such as comparative effectiveness, sequencing of therapy, and advanced dual therapies.”

When it comes to choosing a drug, for example, gastroenterologists are given a general overview of which ones have higher or lower efficacy, but the choice depends on multiple factors, including CD phenotype, previous medications, and patient preference with regard to relative safety, as well as payor preference (although clinicians often try to influence this).

The guidelines align broadly but with some differences with other societal guidelines in the US and Europe. But, said Gemei, the absence of a recommendation for or against treating to a target of endoscopic healing was surprising. “This has been standard practice in recent years based on the updated STRIDE [Selecting Therapeutic Targets in Inflammatory Bowel Disease] consensus statements, as well as recent American College of Gastroenterology guidelines. Though I understand the reason behind this decision, which was simply lack of strong data, it’s still a departure from other society recommendations and current practice. I doubt this will change how we manage our patient, though, and luckily, this is a living guideline, so as more data come out, we should see an update in this area.”

He noted that despite this and other guidelines recommending against the use of 5-aminosalicylic acids in CD, “we still see many of our colleagues using it for their [CD] patients. Hopefully, this guideline can be a helpful resource for everyone trying to update their practice.”

Gemei agreed with the authors that there are persistent knowledge gaps, including insufficient data from head-to-head effectiveness studies, optimal biologic sequencing after failure, advanced combination therapy (such as JAK inhibitors plus anti-interleukin-23), radiologic and endoscopic disease monitoring intervals, and therapy withdrawal strategies after long-term remission. “So there’s a lot we still need to understand better,” he said. “Until we have more data and guidance, we are still practicing all these things based on the available evidence as well as local practice patterns.”

Overall, said Scott, the guidance highlights the options with the best supporting evidence while incorporating the patient’s prior treatment journey. “It’s also important to emphasize that treatment decisions should be individualized and should involve shared decision-making among providers and their patients,” he added. “Patient preferences, age, active comorbidities, and pregnancy should always be considered when selecting the appropriate treatment plan.”

All funding for this guidance was supplied by AGA. The guideline chairs had no conflicts of interest, and fewer than 50% of guideline panel members had conflicts of interest. Gemei had no conflicts of interest.

A version of this article appeared on Medscape.com.

Nonselective beta-blockers (NSBBs) appear to reduce mortality among patients with gastric varices, according to investigators.

In a real-world dataset of patients with gastric varices, NSBBs were associated with a 38% reduced mortality rate, supporting the common belief that protective effects extend across different types of varices, lead author Rebecca H. Moon, MD, of Kaiser Permanente Los Angeles Medical Center, and colleagues, reported.

“Overall, numerous randomized trials have established NSBB efficacy in primary and secondary prevention of esophageal variceal hemorrhage,” the investigators wrote in Gastro Hep Advances. “While these benefits are presumed to extend to gastric varices, empirical data on NSBB efficacy in gastric varices management remain scarce.”

To address this knowledge gap, Moon and colleagues conducted a retrospective cohort study of 1,276 adults (aged 18-75 years) diagnosed with gastric varices between 2015 and 2021 within the Kaiser Permanente Southern California system.

Patients were followed through February 2022. Those with splenectomy, transjugular intrahepatic portosystemic shunt (TIPS) performed outside the system, or use of more than one type of NSBB were excluded. NSBB exposure was defined as therapy initiated within 1 year before or after variceal diagnosis.

Outcomes included gastric and esophageal variceal hemorrhage, TIPS, liver transplantation, and mortality. Multivariable logistic regression was used to compare NSBB users with nonusers and to assess individual effects of different NSBBs while adjusting for baseline characteristics.

The study population had a mean age of 58 years with a male predominance (63%). Approximately half (48%) of the patients were Hispanic. Common comorbidities included hypertension (66%), obesity (49%), and type 2 diabetes (45%). More than half of the patients (52.6%) had coexisting esophageal varices, 38% had ascites, and 22% had a history of hepatic encephalopathy.

In total, 767 patients (62%) received an NSBB. Propranolol and nadolol were most commonly prescribed, while carvedilol use was rare. Median follow-up was 1.1 years.

Overall, 40% of patients died during the study period. Mortality was significantly lower among NSBB users compared with nonusers (39.2% vs 50.9%), corresponding to a 38% reduced risk (odds ratio [OR], 0.62; 95% CI, 0.46–0.84). Nadolol was associated with the lowest mortality risk (OR, 0.55; 95% CI, 0.38–0.79), followed by propranolol (OR, 0.71; 95% CI, 0.50–1.00). Carvedilol use was too infrequent for meaningful analysis.

Rates of gastric variceal hemorrhage (7%), esophageal variceal hemorrhage (22%), TIPS (4%), and liver transplantation (5%) did not differ significantly between NSBB and non-NSBB groups.

“The observed reduction in mortality among NSBB users, particularly those on nadolol, suggests a potential survival benefit,” the investigators wrote. “However, the lack of statistically significant differences in other clinical outcomes, including gastric variceal hemorrhage, esophageal variceal hemorrhage, TIPS, and liver transplantation, indicates that the primary benefit of NSBBs in gastric varices management may be limited to mortality reduction rather than prevention of other complications.”

Moon and colleagues went on to call for additional research.

“Further prospective studies are needed to elucidate the effects of NSBBs on gastric varices and to refine treatment strategies for this high-risk population,” they wrote. “Given the substantial mortality associated with gastric variceal hemorrhage, continued research into novel therapeutic approaches is essential to improving outcomes for patients with gastric varices.”

Publication costs were covered by Kaiser Permanente Los Angeles Medical Education and Research. The investigators disclosed no conflicts of interest.

Nonselective beta-blockers (NSBBs) appear to reduce mortality among patients with gastric varices, according to investigators.

In a real-world dataset of patients with gastric varices, NSBBs were associated with a 38% reduced mortality rate, supporting the common belief that protective effects extend across different types of varices, lead author Rebecca H. Moon, MD, of Kaiser Permanente Los Angeles Medical Center, and colleagues, reported.

“Overall, numerous randomized trials have established NSBB efficacy in primary and secondary prevention of esophageal variceal hemorrhage,” the investigators wrote in Gastro Hep Advances. “While these benefits are presumed to extend to gastric varices, empirical data on NSBB efficacy in gastric varices management remain scarce.”

To address this knowledge gap, Moon and colleagues conducted a retrospective cohort study of 1,276 adults (aged 18-75 years) diagnosed with gastric varices between 2015 and 2021 within the Kaiser Permanente Southern California system.

Patients were followed through February 2022. Those with splenectomy, transjugular intrahepatic portosystemic shunt (TIPS) performed outside the system, or use of more than one type of NSBB were excluded. NSBB exposure was defined as therapy initiated within 1 year before or after variceal diagnosis.

Outcomes included gastric and esophageal variceal hemorrhage, TIPS, liver transplantation, and mortality. Multivariable logistic regression was used to compare NSBB users with nonusers and to assess individual effects of different NSBBs while adjusting for baseline characteristics.

The study population had a mean age of 58 years with a male predominance (63%). Approximately half (48%) of the patients were Hispanic. Common comorbidities included hypertension (66%), obesity (49%), and type 2 diabetes (45%). More than half of the patients (52.6%) had coexisting esophageal varices, 38% had ascites, and 22% had a history of hepatic encephalopathy.

In total, 767 patients (62%) received an NSBB. Propranolol and nadolol were most commonly prescribed, while carvedilol use was rare. Median follow-up was 1.1 years.

Overall, 40% of patients died during the study period. Mortality was significantly lower among NSBB users compared with nonusers (39.2% vs 50.9%), corresponding to a 38% reduced risk (odds ratio [OR], 0.62; 95% CI, 0.46–0.84). Nadolol was associated with the lowest mortality risk (OR, 0.55; 95% CI, 0.38–0.79), followed by propranolol (OR, 0.71; 95% CI, 0.50–1.00). Carvedilol use was too infrequent for meaningful analysis.

Rates of gastric variceal hemorrhage (7%), esophageal variceal hemorrhage (22%), TIPS (4%), and liver transplantation (5%) did not differ significantly between NSBB and non-NSBB groups.

“The observed reduction in mortality among NSBB users, particularly those on nadolol, suggests a potential survival benefit,” the investigators wrote. “However, the lack of statistically significant differences in other clinical outcomes, including gastric variceal hemorrhage, esophageal variceal hemorrhage, TIPS, and liver transplantation, indicates that the primary benefit of NSBBs in gastric varices management may be limited to mortality reduction rather than prevention of other complications.”

Moon and colleagues went on to call for additional research.

“Further prospective studies are needed to elucidate the effects of NSBBs on gastric varices and to refine treatment strategies for this high-risk population,” they wrote. “Given the substantial mortality associated with gastric variceal hemorrhage, continued research into novel therapeutic approaches is essential to improving outcomes for patients with gastric varices.”

Publication costs were covered by Kaiser Permanente Los Angeles Medical Education and Research. The investigators disclosed no conflicts of interest.

Nonselective beta-blockers (NSBBs) appear to reduce mortality among patients with gastric varices, according to investigators.

In a real-world dataset of patients with gastric varices, NSBBs were associated with a 38% reduced mortality rate, supporting the common belief that protective effects extend across different types of varices, lead author Rebecca H. Moon, MD, of Kaiser Permanente Los Angeles Medical Center, and colleagues, reported.

“Overall, numerous randomized trials have established NSBB efficacy in primary and secondary prevention of esophageal variceal hemorrhage,” the investigators wrote in Gastro Hep Advances. “While these benefits are presumed to extend to gastric varices, empirical data on NSBB efficacy in gastric varices management remain scarce.”

To address this knowledge gap, Moon and colleagues conducted a retrospective cohort study of 1,276 adults (aged 18-75 years) diagnosed with gastric varices between 2015 and 2021 within the Kaiser Permanente Southern California system.

Patients were followed through February 2022. Those with splenectomy, transjugular intrahepatic portosystemic shunt (TIPS) performed outside the system, or use of more than one type of NSBB were excluded. NSBB exposure was defined as therapy initiated within 1 year before or after variceal diagnosis.

Outcomes included gastric and esophageal variceal hemorrhage, TIPS, liver transplantation, and mortality. Multivariable logistic regression was used to compare NSBB users with nonusers and to assess individual effects of different NSBBs while adjusting for baseline characteristics.

The study population had a mean age of 58 years with a male predominance (63%). Approximately half (48%) of the patients were Hispanic. Common comorbidities included hypertension (66%), obesity (49%), and type 2 diabetes (45%). More than half of the patients (52.6%) had coexisting esophageal varices, 38% had ascites, and 22% had a history of hepatic encephalopathy.

In total, 767 patients (62%) received an NSBB. Propranolol and nadolol were most commonly prescribed, while carvedilol use was rare. Median follow-up was 1.1 years.

Overall, 40% of patients died during the study period. Mortality was significantly lower among NSBB users compared with nonusers (39.2% vs 50.9%), corresponding to a 38% reduced risk (odds ratio [OR], 0.62; 95% CI, 0.46–0.84). Nadolol was associated with the lowest mortality risk (OR, 0.55; 95% CI, 0.38–0.79), followed by propranolol (OR, 0.71; 95% CI, 0.50–1.00). Carvedilol use was too infrequent for meaningful analysis.

Rates of gastric variceal hemorrhage (7%), esophageal variceal hemorrhage (22%), TIPS (4%), and liver transplantation (5%) did not differ significantly between NSBB and non-NSBB groups.

“The observed reduction in mortality among NSBB users, particularly those on nadolol, suggests a potential survival benefit,” the investigators wrote. “However, the lack of statistically significant differences in other clinical outcomes, including gastric variceal hemorrhage, esophageal variceal hemorrhage, TIPS, and liver transplantation, indicates that the primary benefit of NSBBs in gastric varices management may be limited to mortality reduction rather than prevention of other complications.”

Moon and colleagues went on to call for additional research.

“Further prospective studies are needed to elucidate the effects of NSBBs on gastric varices and to refine treatment strategies for this high-risk population,” they wrote. “Given the substantial mortality associated with gastric variceal hemorrhage, continued research into novel therapeutic approaches is essential to improving outcomes for patients with gastric varices.”

Publication costs were covered by Kaiser Permanente Los Angeles Medical Education and Research. The investigators disclosed no conflicts of interest.

After decades of successful growth, the ambulatory surgery center (ASC) model may be turning a corner, opening up opportunity for office-based endoscopy models, according to a recent practice management editorial published in Clinical Gastroenterology and Hepatology.

Although office endoscopy has been an option, it hasn’t always felt practical or financially viable in the past. However, the paradigm appears to be shifting as ASC-based revenue streams show signs of stress and fail to keep pace with inflation. As healthcare regulatory and economic environments continue to change, gastroenterologists need a new model to support equity, efficiency, and growth in gastrointestinal (GI) care delivery, the authors wrote.

“Through the course of my 40-year career, I’ve been hit with a lot of changes related to regulations, insurance, and the market. You can’t stay entrenched in your old ways. You have to remain pivotable and come up with new strategic positions,” said Lawrence Kosinski, MD, AGAF, lead author and founder of SonarMD and VOCnomics.

During his private practice career, Kosinski built one of the largest GI practices in Illinois, which had seven ASCs and is now part of one of the largest GI groups in the country. Across 30 years of experience with ASCs, Kosinski has watched the reimbursement for professional services decline, as well as for added revenue streams such as pathology and anesthesia.

Looking for a better solution, Kosinski served on the governing board for the American Gastroenterological Association as the councilor for development and growth. During the past 3 years, he has spoken with GI practices and worked with a national anesthesia company — Ambulatory Anesthesia Care — to better understand the office endoscopy setting.

“In the ’90s, all I wanted was to have an ASC because that was in vogue,” he said. “But if you look critically at what has happened to the business of outpatient endoscopy in the past 25 years, you’ll see that professional fees haven’t kept up, and trying to replace that lost revenue is a losing battle.”
 

Considering Financial Shifts

Since 2001, professional reimbursement for colonoscopies has fallen by more than 40% while ASC revenue has risen, decreasing the percentage of revenue from professional fees (from 34% to 23%) and increasing the facility component (from 44% to 60%), Kosinski and colleagues wrote.

When looking at profit, compression of professional service fees appears even greater, especially with surging costs of anesthesia care due to high demand and provider shortages. Beyond that, about a third of ASCs are owned at least partially by national entities, as of 2024, leading to even lower realization of profit.

“The profit margins have really been crushed, so what is a GI doc to do? Go where there is opportunity,” Kosinski said. “The difference between hospitals and ASCs has been compressed, so what about the office?”

The proposed 2026 Medicare Physician Fee Schedule includes a 14% increase in reimbursement for office-based procedures, including endoscopy, as well as a 7% decrease for facility-based procedures.

In several states — such as Illinois, Oregon, Virginia, Washington, and Wisconsin — health plans are introducing programs to promote the transition of outpatient endoscopy to office settings rather than hospital-based or ASC-based settings due to costs, the authors wrote.

“The decision to start offering office-based endoscopy services was an easy one for our practice, as it provides a way for us to provide patients convenient, easy-to-access endoscopy that is high quality yet much more affordable than hospital-based settings,” said Neil Gupta, MD, managing partner at Midwest Digestive Health & Nutrition in Des Plaines, Illinois.

The practice has used office-based endoscopy for nearly 2 years, Gupta said, performing about 5000 GI endoscopy procedures per year.

“As we all try to find better ways to provide high-quality but affordable care for patients, office-based endoscopy is a great way to help achieve those goals,” he said. “Healthcare professionals and patients should all be asking, ‘What type of site am I getting my GI endoscopy scheduled at — hospital, surgery center, or physician’s office?’”
 

Regaining Autonomy and Time

Beyond the financial dynamics, office-based endoscopy can help independent GI practices regain control of their work and time and build sustainable growth for the future, Kosinski and colleagues wrote.

Looking ahead, office-based models can also provide the agility and infrastructure to compete in value-based care models, they wrote. In turn, value-based models can create relevance and resilience in a continually changing healthcare environment.

Without the involvement of ASC managers, investors, or health system partners, physicians retain control of scheduling, clinical protocols, financial decisions, and operational workflows, the authors wrote. This could create better alignment with personal preferences, clinical judgment, and patient needs, they noted.

“GI physicians should no longer feel trapped in a hospital setting where they lack independence and influence over decision-making,” said Rock Rockett, PhD, owner and principal consultant of Rockett Healthcare Strategies, which partners with GI groups nationwide to help with development, accreditation, and payer contracting for office endoscopy.

“GI physicians should also no longer feel trapped in a ‘bad marriage’ with partners in an ASC or partners in a practice who create a difficult work environment,” he said. “The viability of office endoscopy allows them to strike out on their own or set up a new partnership on more equitable terms that are attractive for them.”

Patient safety and quality also appear to be similar or better in office-based settings, based on benchmarking data analyzed so far. Hospital transfers were lower, falls were similar, and patient experience was positive, the authors wrote.

At the same time, Kosinski and colleagues noted the difficulty in shifting to office-based models. Most practices have committed to ASCs, for instance, and adding an office-based room can be challenging. Otherwise, practices already use their available office space and don’t have extra rooms available. In that case, an office endoscopy suite may be best suited for expansion sites, allowing practices to grow into new service areas, they wrote.

“You can’t fight the market. You have to focus on what the market wants and needs,” Kosinski said. “To do that, you have to be able to pivot and change direction, looking for new ways to change your mission. This could be an option to do that.”

Kosinski, Gupta, and Rockett declared having no conflicts of interest other than their current employments.
 

A version of this article appeared on Medscape.com.

After decades of successful growth, the ambulatory surgery center (ASC) model may be turning a corner, opening up opportunity for office-based endoscopy models, according to a recent practice management editorial published in Clinical Gastroenterology and Hepatology.

Although office endoscopy has been an option, it hasn’t always felt practical or financially viable in the past. However, the paradigm appears to be shifting as ASC-based revenue streams show signs of stress and fail to keep pace with inflation. As healthcare regulatory and economic environments continue to change, gastroenterologists need a new model to support equity, efficiency, and growth in gastrointestinal (GI) care delivery, the authors wrote.

“Through the course of my 40-year career, I’ve been hit with a lot of changes related to regulations, insurance, and the market. You can’t stay entrenched in your old ways. You have to remain pivotable and come up with new strategic positions,” said Lawrence Kosinski, MD, AGAF, lead author and founder of SonarMD and VOCnomics.

During his private practice career, Kosinski built one of the largest GI practices in Illinois, which had seven ASCs and is now part of one of the largest GI groups in the country. Across 30 years of experience with ASCs, Kosinski has watched the reimbursement for professional services decline, as well as for added revenue streams such as pathology and anesthesia.

Looking for a better solution, Kosinski served on the governing board for the American Gastroenterological Association as the councilor for development and growth. During the past 3 years, he has spoken with GI practices and worked with a national anesthesia company — Ambulatory Anesthesia Care — to better understand the office endoscopy setting.

“In the ’90s, all I wanted was to have an ASC because that was in vogue,” he said. “But if you look critically at what has happened to the business of outpatient endoscopy in the past 25 years, you’ll see that professional fees haven’t kept up, and trying to replace that lost revenue is a losing battle.”
 

Considering Financial Shifts

Since 2001, professional reimbursement for colonoscopies has fallen by more than 40% while ASC revenue has risen, decreasing the percentage of revenue from professional fees (from 34% to 23%) and increasing the facility component (from 44% to 60%), Kosinski and colleagues wrote.

When looking at profit, compression of professional service fees appears even greater, especially with surging costs of anesthesia care due to high demand and provider shortages. Beyond that, about a third of ASCs are owned at least partially by national entities, as of 2024, leading to even lower realization of profit.

“The profit margins have really been crushed, so what is a GI doc to do? Go where there is opportunity,” Kosinski said. “The difference between hospitals and ASCs has been compressed, so what about the office?”

The proposed 2026 Medicare Physician Fee Schedule includes a 14% increase in reimbursement for office-based procedures, including endoscopy, as well as a 7% decrease for facility-based procedures.

In several states — such as Illinois, Oregon, Virginia, Washington, and Wisconsin — health plans are introducing programs to promote the transition of outpatient endoscopy to office settings rather than hospital-based or ASC-based settings due to costs, the authors wrote.

“The decision to start offering office-based endoscopy services was an easy one for our practice, as it provides a way for us to provide patients convenient, easy-to-access endoscopy that is high quality yet much more affordable than hospital-based settings,” said Neil Gupta, MD, managing partner at Midwest Digestive Health & Nutrition in Des Plaines, Illinois.

The practice has used office-based endoscopy for nearly 2 years, Gupta said, performing about 5000 GI endoscopy procedures per year.

“As we all try to find better ways to provide high-quality but affordable care for patients, office-based endoscopy is a great way to help achieve those goals,” he said. “Healthcare professionals and patients should all be asking, ‘What type of site am I getting my GI endoscopy scheduled at — hospital, surgery center, or physician’s office?’”
 

Regaining Autonomy and Time

Beyond the financial dynamics, office-based endoscopy can help independent GI practices regain control of their work and time and build sustainable growth for the future, Kosinski and colleagues wrote.

Looking ahead, office-based models can also provide the agility and infrastructure to compete in value-based care models, they wrote. In turn, value-based models can create relevance and resilience in a continually changing healthcare environment.

Without the involvement of ASC managers, investors, or health system partners, physicians retain control of scheduling, clinical protocols, financial decisions, and operational workflows, the authors wrote. This could create better alignment with personal preferences, clinical judgment, and patient needs, they noted.

“GI physicians should no longer feel trapped in a hospital setting where they lack independence and influence over decision-making,” said Rock Rockett, PhD, owner and principal consultant of Rockett Healthcare Strategies, which partners with GI groups nationwide to help with development, accreditation, and payer contracting for office endoscopy.

“GI physicians should also no longer feel trapped in a ‘bad marriage’ with partners in an ASC or partners in a practice who create a difficult work environment,” he said. “The viability of office endoscopy allows them to strike out on their own or set up a new partnership on more equitable terms that are attractive for them.”

Patient safety and quality also appear to be similar or better in office-based settings, based on benchmarking data analyzed so far. Hospital transfers were lower, falls were similar, and patient experience was positive, the authors wrote.

At the same time, Kosinski and colleagues noted the difficulty in shifting to office-based models. Most practices have committed to ASCs, for instance, and adding an office-based room can be challenging. Otherwise, practices already use their available office space and don’t have extra rooms available. In that case, an office endoscopy suite may be best suited for expansion sites, allowing practices to grow into new service areas, they wrote.

“You can’t fight the market. You have to focus on what the market wants and needs,” Kosinski said. “To do that, you have to be able to pivot and change direction, looking for new ways to change your mission. This could be an option to do that.”

Kosinski, Gupta, and Rockett declared having no conflicts of interest other than their current employments.
 

A version of this article appeared on Medscape.com.

After decades of successful growth, the ambulatory surgery center (ASC) model may be turning a corner, opening up opportunity for office-based endoscopy models, according to a recent practice management editorial published in Clinical Gastroenterology and Hepatology.

Although office endoscopy has been an option, it hasn’t always felt practical or financially viable in the past. However, the paradigm appears to be shifting as ASC-based revenue streams show signs of stress and fail to keep pace with inflation. As healthcare regulatory and economic environments continue to change, gastroenterologists need a new model to support equity, efficiency, and growth in gastrointestinal (GI) care delivery, the authors wrote.

“Through the course of my 40-year career, I’ve been hit with a lot of changes related to regulations, insurance, and the market. You can’t stay entrenched in your old ways. You have to remain pivotable and come up with new strategic positions,” said Lawrence Kosinski, MD, AGAF, lead author and founder of SonarMD and VOCnomics.

During his private practice career, Kosinski built one of the largest GI practices in Illinois, which had seven ASCs and is now part of one of the largest GI groups in the country. Across 30 years of experience with ASCs, Kosinski has watched the reimbursement for professional services decline, as well as for added revenue streams such as pathology and anesthesia.

Looking for a better solution, Kosinski served on the governing board for the American Gastroenterological Association as the councilor for development and growth. During the past 3 years, he has spoken with GI practices and worked with a national anesthesia company — Ambulatory Anesthesia Care — to better understand the office endoscopy setting.

“In the ’90s, all I wanted was to have an ASC because that was in vogue,” he said. “But if you look critically at what has happened to the business of outpatient endoscopy in the past 25 years, you’ll see that professional fees haven’t kept up, and trying to replace that lost revenue is a losing battle.”
 

Considering Financial Shifts

Since 2001, professional reimbursement for colonoscopies has fallen by more than 40% while ASC revenue has risen, decreasing the percentage of revenue from professional fees (from 34% to 23%) and increasing the facility component (from 44% to 60%), Kosinski and colleagues wrote.

When looking at profit, compression of professional service fees appears even greater, especially with surging costs of anesthesia care due to high demand and provider shortages. Beyond that, about a third of ASCs are owned at least partially by national entities, as of 2024, leading to even lower realization of profit.

“The profit margins have really been crushed, so what is a GI doc to do? Go where there is opportunity,” Kosinski said. “The difference between hospitals and ASCs has been compressed, so what about the office?”

The proposed 2026 Medicare Physician Fee Schedule includes a 14% increase in reimbursement for office-based procedures, including endoscopy, as well as a 7% decrease for facility-based procedures.

In several states — such as Illinois, Oregon, Virginia, Washington, and Wisconsin — health plans are introducing programs to promote the transition of outpatient endoscopy to office settings rather than hospital-based or ASC-based settings due to costs, the authors wrote.

“The decision to start offering office-based endoscopy services was an easy one for our practice, as it provides a way for us to provide patients convenient, easy-to-access endoscopy that is high quality yet much more affordable than hospital-based settings,” said Neil Gupta, MD, managing partner at Midwest Digestive Health & Nutrition in Des Plaines, Illinois.

The practice has used office-based endoscopy for nearly 2 years, Gupta said, performing about 5000 GI endoscopy procedures per year.

“As we all try to find better ways to provide high-quality but affordable care for patients, office-based endoscopy is a great way to help achieve those goals,” he said. “Healthcare professionals and patients should all be asking, ‘What type of site am I getting my GI endoscopy scheduled at — hospital, surgery center, or physician’s office?’”
 

Regaining Autonomy and Time

Beyond the financial dynamics, office-based endoscopy can help independent GI practices regain control of their work and time and build sustainable growth for the future, Kosinski and colleagues wrote.

Looking ahead, office-based models can also provide the agility and infrastructure to compete in value-based care models, they wrote. In turn, value-based models can create relevance and resilience in a continually changing healthcare environment.

Without the involvement of ASC managers, investors, or health system partners, physicians retain control of scheduling, clinical protocols, financial decisions, and operational workflows, the authors wrote. This could create better alignment with personal preferences, clinical judgment, and patient needs, they noted.

“GI physicians should no longer feel trapped in a hospital setting where they lack independence and influence over decision-making,” said Rock Rockett, PhD, owner and principal consultant of Rockett Healthcare Strategies, which partners with GI groups nationwide to help with development, accreditation, and payer contracting for office endoscopy.

“GI physicians should also no longer feel trapped in a ‘bad marriage’ with partners in an ASC or partners in a practice who create a difficult work environment,” he said. “The viability of office endoscopy allows them to strike out on their own or set up a new partnership on more equitable terms that are attractive for them.”

Patient safety and quality also appear to be similar or better in office-based settings, based on benchmarking data analyzed so far. Hospital transfers were lower, falls were similar, and patient experience was positive, the authors wrote.

At the same time, Kosinski and colleagues noted the difficulty in shifting to office-based models. Most practices have committed to ASCs, for instance, and adding an office-based room can be challenging. Otherwise, practices already use their available office space and don’t have extra rooms available. In that case, an office endoscopy suite may be best suited for expansion sites, allowing practices to grow into new service areas, they wrote.

“You can’t fight the market. You have to focus on what the market wants and needs,” Kosinski said. “To do that, you have to be able to pivot and change direction, looking for new ways to change your mission. This could be an option to do that.”

Kosinski, Gupta, and Rockett declared having no conflicts of interest other than their current employments.
 

A version of this article appeared on Medscape.com.

Children with Wilson’s disease (WD) are more likely than are adults to present with acute liver failure or acute-on-chronic liver failure and have lower transplant-free survival, according to data from a large single-center study in India.

These findings underscore the importance of early recognition and genetic evaluation in pediatric patients, and timely consideration of liver transplantation in severe presentations, reported lead author Anand V. Kulkarni, MD, of AIG Hospitals, Hyderabad, India, and colleagues.

“There is a lack of large cohort studies evaluating the clinical presentation of WD, along with a limited understanding of genotype–phenotype correlations in patients with WD presenting with liver disease and the absence of comprehensive comparisons between pediatric and adult outcomes,” the investigators wrote in Gastro Hep Advances (2025 Jun. doi: 10.1016/j.gastha.2025.100717). “Additionally, data on living donor liver transplantation (LDLT) outcomes in WD remain scarce.”

To address these gaps, Kulkarni and colleagues performed a single-center retrospective study of all patients with WD diagnosed and managed at AIG Hospitals between June 2020 and April 2024. 

Diagnosis followed Leipzig criteria, incorporating clinical features, slit-lamp examination for Kayser–Fleischer rings, serum ceruloplasmin, 24-hour urinary copper, hepatic copper when available, and genetic testing when available. 

Patients were stratified by age into pediatric and adult groups. The investigators compared clinical presentation, laboratory parameters, and outcomes across age groups.

Management reflected standard practice at the center: chelation with D-penicillamine or trientine, zinc therapy as monotherapy or adjunctive therapy, plasma exchange for acute liver failure or acute-on-chronic liver failure, and evaluation for living-donor liver transplantation when indicated. Genetic analysis was performed in approximately 70% of the cohort.

The final dataset included 156 patients, with a median age of 19 years (range, 2–57), and an approximately equal split between adult and pediatric groups. 

Presentation differed markedly by age. Among pediatric patients, the most common presentations were acute liver failure (26.7%) and acute-on-chronic liver failure (20%). Adults most frequently presented with decompensated cirrhosis (30.9%). Kayser–Fleischer rings were more prevalent in the pediatric group, consistent with underlying disease despite acute presentation.

Outcomes also varied by age and presentation. On Kaplan–Meier analysis, transplant-free survival was 72% in children and 87.7% in adults after a median follow-up of 1.33 years (P = .01). Overall cohort transplant-free survival at 1.33 years was 80.1%. Thirteen percent of patients underwent LDLT, with 90% 1-year post-transplant survival. Among those who received plasma exchange for acute presentations, transplant-free survival was 40.5%.

Among the patients with genetic data, 54.1% were homozygous or compound heterozygous for combinations of pathogenic variants and variants of uncertain significance in ATP7B. The most frequently observed pathogenic variants were p.Gly977Glu, p.Cys271Ter, and p.Asn1186Ser. Several additional variants, including novel changes, were identified across the cohort. 

No consistent genotype–phenotype correlation was observed. The investigators noted that the center’s focus on liver disease likely enriched the cohort for hepatic presentations, and that some patients were included based on Leipzig scores of 2-3 with supportive clinical response to therapy.

“Further research should focus on identifying structural variants, variants in other genes, and epigenetic modulators of genetic expression,” Kulkarni and colleagues concluded.

The genetic tests were performed with intramural funding support from the Asian Healthcare Foundation, provided to AIG Hospitals Hyderabad. The investigators disclosed no conflicts of interest.

Children with Wilson’s disease (WD) are more likely than are adults to present with acute liver failure or acute-on-chronic liver failure and have lower transplant-free survival, according to data from a large single-center study in India.

These findings underscore the importance of early recognition and genetic evaluation in pediatric patients, and timely consideration of liver transplantation in severe presentations, reported lead author Anand V. Kulkarni, MD, of AIG Hospitals, Hyderabad, India, and colleagues.

“There is a lack of large cohort studies evaluating the clinical presentation of WD, along with a limited understanding of genotype–phenotype correlations in patients with WD presenting with liver disease and the absence of comprehensive comparisons between pediatric and adult outcomes,” the investigators wrote in Gastro Hep Advances (2025 Jun. doi: 10.1016/j.gastha.2025.100717). “Additionally, data on living donor liver transplantation (LDLT) outcomes in WD remain scarce.”

To address these gaps, Kulkarni and colleagues performed a single-center retrospective study of all patients with WD diagnosed and managed at AIG Hospitals between June 2020 and April 2024. 

Diagnosis followed Leipzig criteria, incorporating clinical features, slit-lamp examination for Kayser–Fleischer rings, serum ceruloplasmin, 24-hour urinary copper, hepatic copper when available, and genetic testing when available. 

Patients were stratified by age into pediatric and adult groups. The investigators compared clinical presentation, laboratory parameters, and outcomes across age groups.

Management reflected standard practice at the center: chelation with D-penicillamine or trientine, zinc therapy as monotherapy or adjunctive therapy, plasma exchange for acute liver failure or acute-on-chronic liver failure, and evaluation for living-donor liver transplantation when indicated. Genetic analysis was performed in approximately 70% of the cohort.

The final dataset included 156 patients, with a median age of 19 years (range, 2–57), and an approximately equal split between adult and pediatric groups. 

Presentation differed markedly by age. Among pediatric patients, the most common presentations were acute liver failure (26.7%) and acute-on-chronic liver failure (20%). Adults most frequently presented with decompensated cirrhosis (30.9%). Kayser–Fleischer rings were more prevalent in the pediatric group, consistent with underlying disease despite acute presentation.

Outcomes also varied by age and presentation. On Kaplan–Meier analysis, transplant-free survival was 72% in children and 87.7% in adults after a median follow-up of 1.33 years (P = .01). Overall cohort transplant-free survival at 1.33 years was 80.1%. Thirteen percent of patients underwent LDLT, with 90% 1-year post-transplant survival. Among those who received plasma exchange for acute presentations, transplant-free survival was 40.5%.

Among the patients with genetic data, 54.1% were homozygous or compound heterozygous for combinations of pathogenic variants and variants of uncertain significance in ATP7B. The most frequently observed pathogenic variants were p.Gly977Glu, p.Cys271Ter, and p.Asn1186Ser. Several additional variants, including novel changes, were identified across the cohort. 

No consistent genotype–phenotype correlation was observed. The investigators noted that the center’s focus on liver disease likely enriched the cohort for hepatic presentations, and that some patients were included based on Leipzig scores of 2-3 with supportive clinical response to therapy.

“Further research should focus on identifying structural variants, variants in other genes, and epigenetic modulators of genetic expression,” Kulkarni and colleagues concluded.

The genetic tests were performed with intramural funding support from the Asian Healthcare Foundation, provided to AIG Hospitals Hyderabad. The investigators disclosed no conflicts of interest.

Children with Wilson’s disease (WD) are more likely than are adults to present with acute liver failure or acute-on-chronic liver failure and have lower transplant-free survival, according to data from a large single-center study in India.

These findings underscore the importance of early recognition and genetic evaluation in pediatric patients, and timely consideration of liver transplantation in severe presentations, reported lead author Anand V. Kulkarni, MD, of AIG Hospitals, Hyderabad, India, and colleagues.

“There is a lack of large cohort studies evaluating the clinical presentation of WD, along with a limited understanding of genotype–phenotype correlations in patients with WD presenting with liver disease and the absence of comprehensive comparisons between pediatric and adult outcomes,” the investigators wrote in Gastro Hep Advances (2025 Jun. doi: 10.1016/j.gastha.2025.100717). “Additionally, data on living donor liver transplantation (LDLT) outcomes in WD remain scarce.”

To address these gaps, Kulkarni and colleagues performed a single-center retrospective study of all patients with WD diagnosed and managed at AIG Hospitals between June 2020 and April 2024. 

Diagnosis followed Leipzig criteria, incorporating clinical features, slit-lamp examination for Kayser–Fleischer rings, serum ceruloplasmin, 24-hour urinary copper, hepatic copper when available, and genetic testing when available. 

Patients were stratified by age into pediatric and adult groups. The investigators compared clinical presentation, laboratory parameters, and outcomes across age groups.

Management reflected standard practice at the center: chelation with D-penicillamine or trientine, zinc therapy as monotherapy or adjunctive therapy, plasma exchange for acute liver failure or acute-on-chronic liver failure, and evaluation for living-donor liver transplantation when indicated. Genetic analysis was performed in approximately 70% of the cohort.

The final dataset included 156 patients, with a median age of 19 years (range, 2–57), and an approximately equal split between adult and pediatric groups. 

Presentation differed markedly by age. Among pediatric patients, the most common presentations were acute liver failure (26.7%) and acute-on-chronic liver failure (20%). Adults most frequently presented with decompensated cirrhosis (30.9%). Kayser–Fleischer rings were more prevalent in the pediatric group, consistent with underlying disease despite acute presentation.

Outcomes also varied by age and presentation. On Kaplan–Meier analysis, transplant-free survival was 72% in children and 87.7% in adults after a median follow-up of 1.33 years (P = .01). Overall cohort transplant-free survival at 1.33 years was 80.1%. Thirteen percent of patients underwent LDLT, with 90% 1-year post-transplant survival. Among those who received plasma exchange for acute presentations, transplant-free survival was 40.5%.

Among the patients with genetic data, 54.1% were homozygous or compound heterozygous for combinations of pathogenic variants and variants of uncertain significance in ATP7B. The most frequently observed pathogenic variants were p.Gly977Glu, p.Cys271Ter, and p.Asn1186Ser. Several additional variants, including novel changes, were identified across the cohort. 

No consistent genotype–phenotype correlation was observed. The investigators noted that the center’s focus on liver disease likely enriched the cohort for hepatic presentations, and that some patients were included based on Leipzig scores of 2-3 with supportive clinical response to therapy.

“Further research should focus on identifying structural variants, variants in other genes, and epigenetic modulators of genetic expression,” Kulkarni and colleagues concluded.

The genetic tests were performed with intramural funding support from the Asian Healthcare Foundation, provided to AIG Hospitals Hyderabad. The investigators disclosed no conflicts of interest.

Needle-knife fistulotomy (NKF) is a safe and effective technique for primary biliary access during endoscopic retrograde cholangiopancreatography (ERCP), even among trainee advanced endoscopists, based on results of a randomized trial.

Across procedures conducted predominantly by trainees, safety outcomes were similar between NKF and standard cannulation, and all patients were successfully cannulated, suggesting this is a broadly accessible technique, reported lead author Aleksey Novikov, MD, of the University of Florida College of Medicine, Gainesville, and colleagues, reported.

Writing in Techniques and Innovations in Gastrointestinal Endoscopy, the investigators noted that standard cannulation fails in 5-20% of cases, which has led to development of various alternative techniques, including NKF. To perform the technique, the endoscopist makes a small incision in the intraduodenal biliary segment 3-6mm above the papillary orifice, with cephalad extension until bili-ary access is achieved.

To date, four prospective studies have evaluated NKF in the hands of expert advanced endoscopists. 

“These studies showed that NKF is a safe and useful technique that significantly reduces the risk of PEP in the hands of expert advanced endoscopists,” the investigators wrote. ‘The suggestion that NKF should be restricted to expert advanced endoscopists likely limits widespread use.”

To determine whether NKF is a suitable technique for less experienced endoscopists, the investigators conducted the present single-center, prospective randomized controlled trial at Thomas Jefferson University Hospital in Philadelphia.

Adults undergoing ERCP for biliary indications were randomly assigned in a 1:1 ratio to undergo primary cannulation via NKF or standard cannulation. Patients with prior sphincterotomy, ampullectomy, or unfavorable anatomy were excluded.

A total of 186 patients were randomized, with 137 ultimately included in the per-protocol analysis after exclusions for anatomic factors. Most procedures (72.3%) were performed by advanced endoscopy trainees under direct supervision, 26 procedures (19.0%) were performed by attending endoscopists without substantive prior NKF experience, and 12 (8.8%) by an attending endoscopist with NKF expertise.

“It is important to note that the majority of procedures performed in the context of this study were performed by an advanced endoscopy trainee with no NKF experience or an attending advanced endoscopist with minimal NKF experience,” the investigators wrote.

All patients received prophylactic rectal indomethacin, and cannulation attempts were capped at 20 minutes before crossover to another technique was permitted.

The primary endpoint was incidence of post-ERCP pancreatitis. Secondary endpoints included successful biliary access, time to access, and rates of bleeding and perforation.

Post-ERCP pancreatitis occurred at similar rate across groups: 6 cases (8.2%) in the standard cannulation arm and 5 cases (7.8%) in the NKF arm (P = .93). Rates of bleeding and perforation were also similar for both techniques.

Within the initial 20-minute window, biliary access rates were comparable between groups, at 75.3% and 82.2% for standard cannulation and NKF, respectively (P = .89). Allowing additional attempts or crossover, overall success rose to 100% in both arms.

Mean time to access was longer with NKF, averaging 380 seconds compared with 268 seconds for standard cannulation (P less than .05). 

“NKF was essentially equivalent to standard cannulation in many aspects,” the investigators wrote, calling the two techniques “complementary.”

They also suggested that the relative equivalence between techniques “carries more weight” after considering the low level of NKF experience among participating endoscopists.

“Overall, our data support teaching advanced endoscopy trainees NKF as a primary method of biliary access in patients with favorable anatomy,” the investigators concluded.

The investigators disclosed relationships with Medtronic, Boston Scientific, and Olympus.
 

Needle-knife fistulotomy (NKF) is a safe and effective technique for primary biliary access during endoscopic retrograde cholangiopancreatography (ERCP), even among trainee advanced endoscopists, based on results of a randomized trial.

Across procedures conducted predominantly by trainees, safety outcomes were similar between NKF and standard cannulation, and all patients were successfully cannulated, suggesting this is a broadly accessible technique, reported lead author Aleksey Novikov, MD, of the University of Florida College of Medicine, Gainesville, and colleagues, reported.

Writing in Techniques and Innovations in Gastrointestinal Endoscopy, the investigators noted that standard cannulation fails in 5-20% of cases, which has led to development of various alternative techniques, including NKF. To perform the technique, the endoscopist makes a small incision in the intraduodenal biliary segment 3-6mm above the papillary orifice, with cephalad extension until bili-ary access is achieved.

To date, four prospective studies have evaluated NKF in the hands of expert advanced endoscopists. 

“These studies showed that NKF is a safe and useful technique that significantly reduces the risk of PEP in the hands of expert advanced endoscopists,” the investigators wrote. ‘The suggestion that NKF should be restricted to expert advanced endoscopists likely limits widespread use.”

To determine whether NKF is a suitable technique for less experienced endoscopists, the investigators conducted the present single-center, prospective randomized controlled trial at Thomas Jefferson University Hospital in Philadelphia.

Adults undergoing ERCP for biliary indications were randomly assigned in a 1:1 ratio to undergo primary cannulation via NKF or standard cannulation. Patients with prior sphincterotomy, ampullectomy, or unfavorable anatomy were excluded.

A total of 186 patients were randomized, with 137 ultimately included in the per-protocol analysis after exclusions for anatomic factors. Most procedures (72.3%) were performed by advanced endoscopy trainees under direct supervision, 26 procedures (19.0%) were performed by attending endoscopists without substantive prior NKF experience, and 12 (8.8%) by an attending endoscopist with NKF expertise.

“It is important to note that the majority of procedures performed in the context of this study were performed by an advanced endoscopy trainee with no NKF experience or an attending advanced endoscopist with minimal NKF experience,” the investigators wrote.

All patients received prophylactic rectal indomethacin, and cannulation attempts were capped at 20 minutes before crossover to another technique was permitted.

The primary endpoint was incidence of post-ERCP pancreatitis. Secondary endpoints included successful biliary access, time to access, and rates of bleeding and perforation.

Post-ERCP pancreatitis occurred at similar rate across groups: 6 cases (8.2%) in the standard cannulation arm and 5 cases (7.8%) in the NKF arm (P = .93). Rates of bleeding and perforation were also similar for both techniques.

Within the initial 20-minute window, biliary access rates were comparable between groups, at 75.3% and 82.2% for standard cannulation and NKF, respectively (P = .89). Allowing additional attempts or crossover, overall success rose to 100% in both arms.

Mean time to access was longer with NKF, averaging 380 seconds compared with 268 seconds for standard cannulation (P less than .05). 

“NKF was essentially equivalent to standard cannulation in many aspects,” the investigators wrote, calling the two techniques “complementary.”

They also suggested that the relative equivalence between techniques “carries more weight” after considering the low level of NKF experience among participating endoscopists.

“Overall, our data support teaching advanced endoscopy trainees NKF as a primary method of biliary access in patients with favorable anatomy,” the investigators concluded.

The investigators disclosed relationships with Medtronic, Boston Scientific, and Olympus.
 

Needle-knife fistulotomy (NKF) is a safe and effective technique for primary biliary access during endoscopic retrograde cholangiopancreatography (ERCP), even among trainee advanced endoscopists, based on results of a randomized trial.

Across procedures conducted predominantly by trainees, safety outcomes were similar between NKF and standard cannulation, and all patients were successfully cannulated, suggesting this is a broadly accessible technique, reported lead author Aleksey Novikov, MD, of the University of Florida College of Medicine, Gainesville, and colleagues, reported.

Writing in Techniques and Innovations in Gastrointestinal Endoscopy, the investigators noted that standard cannulation fails in 5-20% of cases, which has led to development of various alternative techniques, including NKF. To perform the technique, the endoscopist makes a small incision in the intraduodenal biliary segment 3-6mm above the papillary orifice, with cephalad extension until bili-ary access is achieved.

To date, four prospective studies have evaluated NKF in the hands of expert advanced endoscopists. 

“These studies showed that NKF is a safe and useful technique that significantly reduces the risk of PEP in the hands of expert advanced endoscopists,” the investigators wrote. ‘The suggestion that NKF should be restricted to expert advanced endoscopists likely limits widespread use.”

To determine whether NKF is a suitable technique for less experienced endoscopists, the investigators conducted the present single-center, prospective randomized controlled trial at Thomas Jefferson University Hospital in Philadelphia.

Adults undergoing ERCP for biliary indications were randomly assigned in a 1:1 ratio to undergo primary cannulation via NKF or standard cannulation. Patients with prior sphincterotomy, ampullectomy, or unfavorable anatomy were excluded.

A total of 186 patients were randomized, with 137 ultimately included in the per-protocol analysis after exclusions for anatomic factors. Most procedures (72.3%) were performed by advanced endoscopy trainees under direct supervision, 26 procedures (19.0%) were performed by attending endoscopists without substantive prior NKF experience, and 12 (8.8%) by an attending endoscopist with NKF expertise.

“It is important to note that the majority of procedures performed in the context of this study were performed by an advanced endoscopy trainee with no NKF experience or an attending advanced endoscopist with minimal NKF experience,” the investigators wrote.

All patients received prophylactic rectal indomethacin, and cannulation attempts were capped at 20 minutes before crossover to another technique was permitted.

The primary endpoint was incidence of post-ERCP pancreatitis. Secondary endpoints included successful biliary access, time to access, and rates of bleeding and perforation.

Post-ERCP pancreatitis occurred at similar rate across groups: 6 cases (8.2%) in the standard cannulation arm and 5 cases (7.8%) in the NKF arm (P = .93). Rates of bleeding and perforation were also similar for both techniques.

Within the initial 20-minute window, biliary access rates were comparable between groups, at 75.3% and 82.2% for standard cannulation and NKF, respectively (P = .89). Allowing additional attempts or crossover, overall success rose to 100% in both arms.

Mean time to access was longer with NKF, averaging 380 seconds compared with 268 seconds for standard cannulation (P less than .05). 

“NKF was essentially equivalent to standard cannulation in many aspects,” the investigators wrote, calling the two techniques “complementary.”

They also suggested that the relative equivalence between techniques “carries more weight” after considering the low level of NKF experience among participating endoscopists.

“Overall, our data support teaching advanced endoscopy trainees NKF as a primary method of biliary access in patients with favorable anatomy,” the investigators concluded.

The investigators disclosed relationships with Medtronic, Boston Scientific, and Olympus.
 

New pharmacologic options approved by the FDA are set to alter the treatment landscape of metabolic dysfunction-associated steatotic liver disease (MASLD), according to the authors of clinical reviews who offered guidance on the pros and cons of resmetirom and semaglutide.

MASLD has become one of the most common causes of chronic liver disease due to the increased prevalence of diabetes, obesity, and other metabolic disorders, Joanne Lin, DO, an internist in the Division of Gastroenterology and Hepatology at the University of California, San Francisco, and colleagues wrote, in a review published in the Journal of Clinical Gastroenterology.

Its complexity makes MASLD challenging to manage. Metabolic, genetic, and environmental factors are involved in the disease, so patients require multidisciplinary and individualized care, Lin told GI & Hepatology News.

Weight loss, dietary changes, and exercise had long been the only treatment approach clinicians could offer patients. But the approval of two drugs — the thyroid hormone receptor-beta agonist resmetirom and the GLP-1 receptor agonist (RA) semaglutide — for patients whose MASLD has advanced to metabolic dysfunction-associated steatohepatitis (MASH) gives physicians new options for patients with severe disease.

In the review, published online before the official approval of semaglutide, Lin and colleagues proposed an algorithm to guide clinicians in choosing a pharmacological therapy for MASLD. “Resmetirom should be primarily used to reverse fibrosis for patients with MASLD and F2-F3 stages, while GLP-1 RAs are beneficial in managing metabolic comorbidities and weight loss in patients with MASLD,” the researchers concluded.

 

GLP-1 Power and Potential

In August 2025, the FDA approved semaglutide for MASH and cited evidence from the ESSENCE trial in its decision.

The ESSENCE study, published in The New England Journal of Medicine, showed significantly higher rates of resolution of steatohepatitis without worsening of fibrosis and reduction in liver fibrosis without worsening steatohepatitis in patients with MASH and moderate or advanced liver fibrosis who received 2.4 mg of once-weekly semaglutide compared with patients who received placebo.

The most common adverse events reported with GLP-1 RAs are gastrointestinal-related, including nausea, diarrhea, vomiting, and constipation, and are mainly mild-to-moderate and dose dependent, Lin and colleagues noted in their review.

GLP-1s have some limitations, Lin said. “GLP-1s are great for weight loss and metabolic risk reduction, but studies are still ongoing to determine their effect on liver histology and reversing fibrosis/cirrhosis,” she said. Some patients seeking these medications also have trouble obtaining them because of their popularity for weight loss, she noted.

 

Resmetirom Shows Success

Resmetirom has demonstrated ability to target hepatocytes and increase the hepatic metabolism of lipids, Lin and colleagues wrote in their review.

Several trials have examined resmetirom as a treatment for MASH, notably the landmark MAESTRO-NASH study , a randomized, placebo-controlled trial of nearly 1000 adults with biopsy-confirmed MASH and stage F2 or F3 fibrosis, which was the basis for the FDA’s approval of the drug in 2024. In the study, 25.9% of the patients treated with 80 mg of resmetirom and 29.9% treated with 100 mg resmetirom achieved MASH resolution with no increase in fibrosis compared with 9.7% of patients treated with placebo. In addition, 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group achieved fibrosis improvement by at least one stage without worsening of MASLD activity scores compared with 14.2% of patients treated with placebo.

The most common reported side effects from resmetirom are diarrhea or constipation, nausea or vomiting, and abdominal pain.

“The limitations of resmetirom include the absence of validated predictors for individual patient response, and no societal guidelines are available to determine when to stop the medication if ineffective,” Lin told GI & Hepatology News. In addition, resmetirom is currently only recommended for a subset of patients with F2-F3 fibrosis, based on the existing trial, she said.

Other limitations include its high cost, which restricts access to the drug for some patients, and lack of long-term safety and efficacy data, Lin added.

 

Weighing the Options

Comparing the emerging agents in the context of MASLD/MASH is important to help clinicians understand how different patient populations respond and guide evidence-based treatment decisions, said Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, in an interview.

“The choice of therapy should be individualized based on comorbidities,” said Ayesh, the lead author of a 2024 review published in Biomedicines that compared resmetirom, GLP-1 agonists, and fibroblast growth factor 21 analogs.

“For example, a GLP-1 receptor agonist may be more appropriate for patients with coexisting diabetes or obesity, while resmetirom may be better suited for patients with more advanced liver disease or minimal metabolic comorbidities,” he said.

GLP-1 RAs, such as semaglutide, offer benefits for diabetes, obesity, and metabolic dysfunction in patients with MASLD/MASH and may be more accessible and cost effective, Ayesh told GI & Hepatology News. However, some patients may experience gastrointestinal side effects or be unable to tolerate GLP-1 RAs, he noted.

By contrast, resmetirom may be preferable for patients with low BMI, advanced fibrosis, or an inability to tolerate GLP-1s, as resmetirom directly targets hepatic pathways involved in MASLD/MASH progression, Ayesh said.

 

Next Steps to Inform Practice

“More research is needed to validate noninvasive biomarkers to monitor response to these medications, determine predictors of efficacy, and evaluate the additive effects, safety, and drug-drug interactions of combination therapy,” Lin said.

Studies are needed to determine both medications’ effects on patients with advanced fibrosis/cirrhosis and special populations, such as individuals with advanced renal disease or posttransplant patients, she added. More studies are expected to inform clinical practice and proper guidelines for the treatment of MASLD, as has been the case with chronic diseases such as hypertension and diabetes, Lin said.

Long-term safety and efficacy data are critical, as most trials of the newly approved medications have had relatively short follow-up periods of approximately 1 year, Ayesh said. “We need real-world evidence and longitudinal studies spanning 3-5 years to confirm sustained efficacy and safety,” he said. Research on cost effectiveness and health-system impacts will be essential to guide policy and ensure equitable access to the medications, he added.

The study by Lin and colleagues received no outside funding. The researchers had no financial conflicts to disclose. Ayesh had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

New pharmacologic options approved by the FDA are set to alter the treatment landscape of metabolic dysfunction-associated steatotic liver disease (MASLD), according to the authors of clinical reviews who offered guidance on the pros and cons of resmetirom and semaglutide.

MASLD has become one of the most common causes of chronic liver disease due to the increased prevalence of diabetes, obesity, and other metabolic disorders, Joanne Lin, DO, an internist in the Division of Gastroenterology and Hepatology at the University of California, San Francisco, and colleagues wrote, in a review published in the Journal of Clinical Gastroenterology.

Its complexity makes MASLD challenging to manage. Metabolic, genetic, and environmental factors are involved in the disease, so patients require multidisciplinary and individualized care, Lin told GI & Hepatology News.

Weight loss, dietary changes, and exercise had long been the only treatment approach clinicians could offer patients. But the approval of two drugs — the thyroid hormone receptor-beta agonist resmetirom and the GLP-1 receptor agonist (RA) semaglutide — for patients whose MASLD has advanced to metabolic dysfunction-associated steatohepatitis (MASH) gives physicians new options for patients with severe disease.

In the review, published online before the official approval of semaglutide, Lin and colleagues proposed an algorithm to guide clinicians in choosing a pharmacological therapy for MASLD. “Resmetirom should be primarily used to reverse fibrosis for patients with MASLD and F2-F3 stages, while GLP-1 RAs are beneficial in managing metabolic comorbidities and weight loss in patients with MASLD,” the researchers concluded.

 

GLP-1 Power and Potential

In August 2025, the FDA approved semaglutide for MASH and cited evidence from the ESSENCE trial in its decision.

The ESSENCE study, published in The New England Journal of Medicine, showed significantly higher rates of resolution of steatohepatitis without worsening of fibrosis and reduction in liver fibrosis without worsening steatohepatitis in patients with MASH and moderate or advanced liver fibrosis who received 2.4 mg of once-weekly semaglutide compared with patients who received placebo.

The most common adverse events reported with GLP-1 RAs are gastrointestinal-related, including nausea, diarrhea, vomiting, and constipation, and are mainly mild-to-moderate and dose dependent, Lin and colleagues noted in their review.

GLP-1s have some limitations, Lin said. “GLP-1s are great for weight loss and metabolic risk reduction, but studies are still ongoing to determine their effect on liver histology and reversing fibrosis/cirrhosis,” she said. Some patients seeking these medications also have trouble obtaining them because of their popularity for weight loss, she noted.

 

Resmetirom Shows Success

Resmetirom has demonstrated ability to target hepatocytes and increase the hepatic metabolism of lipids, Lin and colleagues wrote in their review.

Several trials have examined resmetirom as a treatment for MASH, notably the landmark MAESTRO-NASH study , a randomized, placebo-controlled trial of nearly 1000 adults with biopsy-confirmed MASH and stage F2 or F3 fibrosis, which was the basis for the FDA’s approval of the drug in 2024. In the study, 25.9% of the patients treated with 80 mg of resmetirom and 29.9% treated with 100 mg resmetirom achieved MASH resolution with no increase in fibrosis compared with 9.7% of patients treated with placebo. In addition, 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group achieved fibrosis improvement by at least one stage without worsening of MASLD activity scores compared with 14.2% of patients treated with placebo.

The most common reported side effects from resmetirom are diarrhea or constipation, nausea or vomiting, and abdominal pain.

“The limitations of resmetirom include the absence of validated predictors for individual patient response, and no societal guidelines are available to determine when to stop the medication if ineffective,” Lin told GI & Hepatology News. In addition, resmetirom is currently only recommended for a subset of patients with F2-F3 fibrosis, based on the existing trial, she said.

Other limitations include its high cost, which restricts access to the drug for some patients, and lack of long-term safety and efficacy data, Lin added.

 

Weighing the Options

Comparing the emerging agents in the context of MASLD/MASH is important to help clinicians understand how different patient populations respond and guide evidence-based treatment decisions, said Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, in an interview.

“The choice of therapy should be individualized based on comorbidities,” said Ayesh, the lead author of a 2024 review published in Biomedicines that compared resmetirom, GLP-1 agonists, and fibroblast growth factor 21 analogs.

“For example, a GLP-1 receptor agonist may be more appropriate for patients with coexisting diabetes or obesity, while resmetirom may be better suited for patients with more advanced liver disease or minimal metabolic comorbidities,” he said.

GLP-1 RAs, such as semaglutide, offer benefits for diabetes, obesity, and metabolic dysfunction in patients with MASLD/MASH and may be more accessible and cost effective, Ayesh told GI & Hepatology News. However, some patients may experience gastrointestinal side effects or be unable to tolerate GLP-1 RAs, he noted.

By contrast, resmetirom may be preferable for patients with low BMI, advanced fibrosis, or an inability to tolerate GLP-1s, as resmetirom directly targets hepatic pathways involved in MASLD/MASH progression, Ayesh said.

 

Next Steps to Inform Practice

“More research is needed to validate noninvasive biomarkers to monitor response to these medications, determine predictors of efficacy, and evaluate the additive effects, safety, and drug-drug interactions of combination therapy,” Lin said.

Studies are needed to determine both medications’ effects on patients with advanced fibrosis/cirrhosis and special populations, such as individuals with advanced renal disease or posttransplant patients, she added. More studies are expected to inform clinical practice and proper guidelines for the treatment of MASLD, as has been the case with chronic diseases such as hypertension and diabetes, Lin said.

Long-term safety and efficacy data are critical, as most trials of the newly approved medications have had relatively short follow-up periods of approximately 1 year, Ayesh said. “We need real-world evidence and longitudinal studies spanning 3-5 years to confirm sustained efficacy and safety,” he said. Research on cost effectiveness and health-system impacts will be essential to guide policy and ensure equitable access to the medications, he added.

The study by Lin and colleagues received no outside funding. The researchers had no financial conflicts to disclose. Ayesh had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

New pharmacologic options approved by the FDA are set to alter the treatment landscape of metabolic dysfunction-associated steatotic liver disease (MASLD), according to the authors of clinical reviews who offered guidance on the pros and cons of resmetirom and semaglutide.

MASLD has become one of the most common causes of chronic liver disease due to the increased prevalence of diabetes, obesity, and other metabolic disorders, Joanne Lin, DO, an internist in the Division of Gastroenterology and Hepatology at the University of California, San Francisco, and colleagues wrote, in a review published in the Journal of Clinical Gastroenterology.

Its complexity makes MASLD challenging to manage. Metabolic, genetic, and environmental factors are involved in the disease, so patients require multidisciplinary and individualized care, Lin told GI & Hepatology News.

Weight loss, dietary changes, and exercise had long been the only treatment approach clinicians could offer patients. But the approval of two drugs — the thyroid hormone receptor-beta agonist resmetirom and the GLP-1 receptor agonist (RA) semaglutide — for patients whose MASLD has advanced to metabolic dysfunction-associated steatohepatitis (MASH) gives physicians new options for patients with severe disease.

In the review, published online before the official approval of semaglutide, Lin and colleagues proposed an algorithm to guide clinicians in choosing a pharmacological therapy for MASLD. “Resmetirom should be primarily used to reverse fibrosis for patients with MASLD and F2-F3 stages, while GLP-1 RAs are beneficial in managing metabolic comorbidities and weight loss in patients with MASLD,” the researchers concluded.

 

GLP-1 Power and Potential

In August 2025, the FDA approved semaglutide for MASH and cited evidence from the ESSENCE trial in its decision.

The ESSENCE study, published in The New England Journal of Medicine, showed significantly higher rates of resolution of steatohepatitis without worsening of fibrosis and reduction in liver fibrosis without worsening steatohepatitis in patients with MASH and moderate or advanced liver fibrosis who received 2.4 mg of once-weekly semaglutide compared with patients who received placebo.

The most common adverse events reported with GLP-1 RAs are gastrointestinal-related, including nausea, diarrhea, vomiting, and constipation, and are mainly mild-to-moderate and dose dependent, Lin and colleagues noted in their review.

GLP-1s have some limitations, Lin said. “GLP-1s are great for weight loss and metabolic risk reduction, but studies are still ongoing to determine their effect on liver histology and reversing fibrosis/cirrhosis,” she said. Some patients seeking these medications also have trouble obtaining them because of their popularity for weight loss, she noted.

 

Resmetirom Shows Success

Resmetirom has demonstrated ability to target hepatocytes and increase the hepatic metabolism of lipids, Lin and colleagues wrote in their review.

Several trials have examined resmetirom as a treatment for MASH, notably the landmark MAESTRO-NASH study , a randomized, placebo-controlled trial of nearly 1000 adults with biopsy-confirmed MASH and stage F2 or F3 fibrosis, which was the basis for the FDA’s approval of the drug in 2024. In the study, 25.9% of the patients treated with 80 mg of resmetirom and 29.9% treated with 100 mg resmetirom achieved MASH resolution with no increase in fibrosis compared with 9.7% of patients treated with placebo. In addition, 24.2% of the patients in the 80-mg resmetirom group and 25.9% of those in the 100-mg resmetirom group achieved fibrosis improvement by at least one stage without worsening of MASLD activity scores compared with 14.2% of patients treated with placebo.

The most common reported side effects from resmetirom are diarrhea or constipation, nausea or vomiting, and abdominal pain.

“The limitations of resmetirom include the absence of validated predictors for individual patient response, and no societal guidelines are available to determine when to stop the medication if ineffective,” Lin told GI & Hepatology News. In addition, resmetirom is currently only recommended for a subset of patients with F2-F3 fibrosis, based on the existing trial, she said.

Other limitations include its high cost, which restricts access to the drug for some patients, and lack of long-term safety and efficacy data, Lin added.

 

Weighing the Options

Comparing the emerging agents in the context of MASLD/MASH is important to help clinicians understand how different patient populations respond and guide evidence-based treatment decisions, said Hazem Ayesh, MD, an endocrinologist at Deaconess Health System, Evansville, Indiana, in an interview.

“The choice of therapy should be individualized based on comorbidities,” said Ayesh, the lead author of a 2024 review published in Biomedicines that compared resmetirom, GLP-1 agonists, and fibroblast growth factor 21 analogs.

“For example, a GLP-1 receptor agonist may be more appropriate for patients with coexisting diabetes or obesity, while resmetirom may be better suited for patients with more advanced liver disease or minimal metabolic comorbidities,” he said.

GLP-1 RAs, such as semaglutide, offer benefits for diabetes, obesity, and metabolic dysfunction in patients with MASLD/MASH and may be more accessible and cost effective, Ayesh told GI & Hepatology News. However, some patients may experience gastrointestinal side effects or be unable to tolerate GLP-1 RAs, he noted.

By contrast, resmetirom may be preferable for patients with low BMI, advanced fibrosis, or an inability to tolerate GLP-1s, as resmetirom directly targets hepatic pathways involved in MASLD/MASH progression, Ayesh said.

 

Next Steps to Inform Practice

“More research is needed to validate noninvasive biomarkers to monitor response to these medications, determine predictors of efficacy, and evaluate the additive effects, safety, and drug-drug interactions of combination therapy,” Lin said.

Studies are needed to determine both medications’ effects on patients with advanced fibrosis/cirrhosis and special populations, such as individuals with advanced renal disease or posttransplant patients, she added. More studies are expected to inform clinical practice and proper guidelines for the treatment of MASLD, as has been the case with chronic diseases such as hypertension and diabetes, Lin said.

Long-term safety and efficacy data are critical, as most trials of the newly approved medications have had relatively short follow-up periods of approximately 1 year, Ayesh said. “We need real-world evidence and longitudinal studies spanning 3-5 years to confirm sustained efficacy and safety,” he said. Research on cost effectiveness and health-system impacts will be essential to guide policy and ensure equitable access to the medications, he added.

The study by Lin and colleagues received no outside funding. The researchers had no financial conflicts to disclose. Ayesh had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A large real-world study found that fewer than half of adults who started colorectal cancer (CRC) screening with an at-home stool test completed the recommended repeat test, creating gaps in protection and potentially diminishing their benefits.

Among those who did repeat the test, the average delay was 3 months before COVID and increased to 5 months during the pandemic, the authors reported in BMJ Public Health.

“Stool tests are relatively easy to complete at home and mailed for testing, and they are inexpensive, but they must be completed annually. In contrast, colonoscopies are more invasive and require more time away from work but only need to be repeated every 5-10 years,” Staci J Wendt, PhD, director, health research accelerator, Providence Research Network, Providence, Rhode Island, told GI & Hepatology News.

In the end, “the best colorectal cancer screening test is the one that gets done,” Wendt said.

“This is why we stress the importance of patients and their doctor having these discussions together and deciding which screening is the most preferred method for the individual patient,” she added.

 

Stool Tests Gaining Traction

Adults are increasingly turning to at-home stool tests for CRC screening — a trend that accelerated during the pandemic. Yet, there is limited data on whether patients undergo repeat stool tests following initial negative test results.

Wendt and her colleagues documented rates of repeat preventative stool tests by analyzing electronic medical records from Providence St Joseph Health, a large health system with 51 hospitals and over 1000 clinics across seven western US states.

They divided their analysis into two periods based on the onset of the pandemic. The pre-COVID onset period spanned January 2018 to February 2020 and the post-COVID period spanned March 2020 to February 2022.

“The pandemic is a salient time to conduct this study because it resulted in a dramatic decrease in colonoscopies, which were partially replaced by stool tests. This partial replacement of colonoscopies by stool tests has led other studies to conclude that stool tests mitigated gaps in CRC screening during the pandemic. But gaps may persist if patients do not undergo repeat testing,” the study team explained.

Their sample included 403,085 patients. Among those with an initial negative stool test, the share who obtained a timely repeat screening ranged from 38% to 49% across the study years, confirming that “most patients do not undergo the recommended repeat screening after their initial stool test,” the researchers said.

Among adults who do a repeat test, delays were common. The average lag to the follow-up test was 3months on average, increasing to about 5 months amid COVID — almost half as long as the preventative screening period of stool tests (12 months).

“These gaps could delay detection of CRC and subsequent treatment, potentially resulting in higher mortality. These gaps are particularly important as more and more patients use stool tests instead of colonoscopes for CRC screening,” the researchers wrote.

Screening patterns shifted markedly during the pandemic.

Not surprisingly, the volume of colonoscopies declined substantially after the onset of the pandemic and stayed low through the study’s end. In contrast, the volume of at-home stool tests was increasing before the pandemic and accelerated during the pandemic.

“Given this increase in stool tests, it will be increasingly important to focus on improving long-term adherence to screening through outreach, policies and programs,” the researchers said.

 

A Multilevel Approach

Wendt said health systems that are incorporating proactive measures like sending stool kits to patients who are eligible for screening, should ensure that these screening kits and information are sent annually and that it is stressed that the screening must happen every year.

Reached for comment, Aasma Shaukat, MD, MPH, AGAF, director of outcomes research, Division of Gastroenterology and Hepatology, NYU Langone Health, New York City, who wasn’t involved in the study, said the poor adherence to repeat stool tests for CRC screening seen in this study is “not surprising.”

“We know that adherence goes down with each consecutive screening round and what is really needed is an organized program to keep the level of adherence up,” Shaukat told GI & Hepatology News.

Shaukat agreed that boosting adherence to stool tests requires a “multilevel approach.”

She cited the success of the CRC screening program implemented across Kaiser Permanente Northern California. The program includes proactive and targeted outreach to members who are overdue for screening and mailed fecal immunochemical test kits for at-home use.

As reported previously by GI & Hepatology News, the program has made a huge difference in CRC incidence, deaths, and racial disparities.

The program has doubled the proportion of people up to date with screening. And, within about 10 years, cancer rates were cut by a third, deaths were halved and largely eliminated long-standing differences by race and ethnicity.

The study had no commercial funding. Wendt and Shaukat declared having no relevant disclosures.

 

A version of this article appeared on Medscape.com.

A large real-world study found that fewer than half of adults who started colorectal cancer (CRC) screening with an at-home stool test completed the recommended repeat test, creating gaps in protection and potentially diminishing their benefits.

Among those who did repeat the test, the average delay was 3 months before COVID and increased to 5 months during the pandemic, the authors reported in BMJ Public Health.

“Stool tests are relatively easy to complete at home and mailed for testing, and they are inexpensive, but they must be completed annually. In contrast, colonoscopies are more invasive and require more time away from work but only need to be repeated every 5-10 years,” Staci J Wendt, PhD, director, health research accelerator, Providence Research Network, Providence, Rhode Island, told GI & Hepatology News.

In the end, “the best colorectal cancer screening test is the one that gets done,” Wendt said.

“This is why we stress the importance of patients and their doctor having these discussions together and deciding which screening is the most preferred method for the individual patient,” she added.

 

Stool Tests Gaining Traction

Adults are increasingly turning to at-home stool tests for CRC screening — a trend that accelerated during the pandemic. Yet, there is limited data on whether patients undergo repeat stool tests following initial negative test results.

Wendt and her colleagues documented rates of repeat preventative stool tests by analyzing electronic medical records from Providence St Joseph Health, a large health system with 51 hospitals and over 1000 clinics across seven western US states.

They divided their analysis into two periods based on the onset of the pandemic. The pre-COVID onset period spanned January 2018 to February 2020 and the post-COVID period spanned March 2020 to February 2022.

“The pandemic is a salient time to conduct this study because it resulted in a dramatic decrease in colonoscopies, which were partially replaced by stool tests. This partial replacement of colonoscopies by stool tests has led other studies to conclude that stool tests mitigated gaps in CRC screening during the pandemic. But gaps may persist if patients do not undergo repeat testing,” the study team explained.

Their sample included 403,085 patients. Among those with an initial negative stool test, the share who obtained a timely repeat screening ranged from 38% to 49% across the study years, confirming that “most patients do not undergo the recommended repeat screening after their initial stool test,” the researchers said.

Among adults who do a repeat test, delays were common. The average lag to the follow-up test was 3months on average, increasing to about 5 months amid COVID — almost half as long as the preventative screening period of stool tests (12 months).

“These gaps could delay detection of CRC and subsequent treatment, potentially resulting in higher mortality. These gaps are particularly important as more and more patients use stool tests instead of colonoscopes for CRC screening,” the researchers wrote.

Screening patterns shifted markedly during the pandemic.

Not surprisingly, the volume of colonoscopies declined substantially after the onset of the pandemic and stayed low through the study’s end. In contrast, the volume of at-home stool tests was increasing before the pandemic and accelerated during the pandemic.

“Given this increase in stool tests, it will be increasingly important to focus on improving long-term adherence to screening through outreach, policies and programs,” the researchers said.

 

A Multilevel Approach

Wendt said health systems that are incorporating proactive measures like sending stool kits to patients who are eligible for screening, should ensure that these screening kits and information are sent annually and that it is stressed that the screening must happen every year.

Reached for comment, Aasma Shaukat, MD, MPH, AGAF, director of outcomes research, Division of Gastroenterology and Hepatology, NYU Langone Health, New York City, who wasn’t involved in the study, said the poor adherence to repeat stool tests for CRC screening seen in this study is “not surprising.”

“We know that adherence goes down with each consecutive screening round and what is really needed is an organized program to keep the level of adherence up,” Shaukat told GI & Hepatology News.

Shaukat agreed that boosting adherence to stool tests requires a “multilevel approach.”

She cited the success of the CRC screening program implemented across Kaiser Permanente Northern California. The program includes proactive and targeted outreach to members who are overdue for screening and mailed fecal immunochemical test kits for at-home use.

As reported previously by GI & Hepatology News, the program has made a huge difference in CRC incidence, deaths, and racial disparities.

The program has doubled the proportion of people up to date with screening. And, within about 10 years, cancer rates were cut by a third, deaths were halved and largely eliminated long-standing differences by race and ethnicity.

The study had no commercial funding. Wendt and Shaukat declared having no relevant disclosures.

 

A version of this article appeared on Medscape.com.

A large real-world study found that fewer than half of adults who started colorectal cancer (CRC) screening with an at-home stool test completed the recommended repeat test, creating gaps in protection and potentially diminishing their benefits.

Among those who did repeat the test, the average delay was 3 months before COVID and increased to 5 months during the pandemic, the authors reported in BMJ Public Health.

“Stool tests are relatively easy to complete at home and mailed for testing, and they are inexpensive, but they must be completed annually. In contrast, colonoscopies are more invasive and require more time away from work but only need to be repeated every 5-10 years,” Staci J Wendt, PhD, director, health research accelerator, Providence Research Network, Providence, Rhode Island, told GI & Hepatology News.

In the end, “the best colorectal cancer screening test is the one that gets done,” Wendt said.

“This is why we stress the importance of patients and their doctor having these discussions together and deciding which screening is the most preferred method for the individual patient,” she added.

 

Stool Tests Gaining Traction

Adults are increasingly turning to at-home stool tests for CRC screening — a trend that accelerated during the pandemic. Yet, there is limited data on whether patients undergo repeat stool tests following initial negative test results.

Wendt and her colleagues documented rates of repeat preventative stool tests by analyzing electronic medical records from Providence St Joseph Health, a large health system with 51 hospitals and over 1000 clinics across seven western US states.

They divided their analysis into two periods based on the onset of the pandemic. The pre-COVID onset period spanned January 2018 to February 2020 and the post-COVID period spanned March 2020 to February 2022.

“The pandemic is a salient time to conduct this study because it resulted in a dramatic decrease in colonoscopies, which were partially replaced by stool tests. This partial replacement of colonoscopies by stool tests has led other studies to conclude that stool tests mitigated gaps in CRC screening during the pandemic. But gaps may persist if patients do not undergo repeat testing,” the study team explained.

Their sample included 403,085 patients. Among those with an initial negative stool test, the share who obtained a timely repeat screening ranged from 38% to 49% across the study years, confirming that “most patients do not undergo the recommended repeat screening after their initial stool test,” the researchers said.

Among adults who do a repeat test, delays were common. The average lag to the follow-up test was 3months on average, increasing to about 5 months amid COVID — almost half as long as the preventative screening period of stool tests (12 months).

“These gaps could delay detection of CRC and subsequent treatment, potentially resulting in higher mortality. These gaps are particularly important as more and more patients use stool tests instead of colonoscopes for CRC screening,” the researchers wrote.

Screening patterns shifted markedly during the pandemic.

Not surprisingly, the volume of colonoscopies declined substantially after the onset of the pandemic and stayed low through the study’s end. In contrast, the volume of at-home stool tests was increasing before the pandemic and accelerated during the pandemic.

“Given this increase in stool tests, it will be increasingly important to focus on improving long-term adherence to screening through outreach, policies and programs,” the researchers said.

 

A Multilevel Approach

Wendt said health systems that are incorporating proactive measures like sending stool kits to patients who are eligible for screening, should ensure that these screening kits and information are sent annually and that it is stressed that the screening must happen every year.

Reached for comment, Aasma Shaukat, MD, MPH, AGAF, director of outcomes research, Division of Gastroenterology and Hepatology, NYU Langone Health, New York City, who wasn’t involved in the study, said the poor adherence to repeat stool tests for CRC screening seen in this study is “not surprising.”

“We know that adherence goes down with each consecutive screening round and what is really needed is an organized program to keep the level of adherence up,” Shaukat told GI & Hepatology News.

Shaukat agreed that boosting adherence to stool tests requires a “multilevel approach.”

She cited the success of the CRC screening program implemented across Kaiser Permanente Northern California. The program includes proactive and targeted outreach to members who are overdue for screening and mailed fecal immunochemical test kits for at-home use.

As reported previously by GI & Hepatology News, the program has made a huge difference in CRC incidence, deaths, and racial disparities.

The program has doubled the proportion of people up to date with screening. And, within about 10 years, cancer rates were cut by a third, deaths were halved and largely eliminated long-standing differences by race and ethnicity.

The study had no commercial funding. Wendt and Shaukat declared having no relevant disclosures.

 

A version of this article appeared on Medscape.com.