Gastroenterology

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.

PHOENIX — Users of e-cigarettes had increased odds of peptic ulcer disease (PUD) compared to those who have never used them, a cross-sectional study found.

The study also found increased risk of PUD among former users of e-cigarettes, reported Albert E. Ohrin, MBChB, MHS, of Ascension Saint Agnes Hospital, Baltimore, Maryland, who presented the study here at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting. 

While cigarette smoking is a known risk factor for PUD, there was little in the literature investigating whether vaping has a similar risk profile, said Ohrin, a first-year internal medicine resident. He told GI & Hepatology News he found e-cigarette users on Reddit discussing worsening PUD and decided to investigate further, especially since vaping is so popular among young people.

E-cigarettes are the most-used tobacco product among middle and high school students. The National Youth Tobacco Survey in the US reported that 1.6 million students (5.9%) vaped in 2024, a decline from 7.7% in 2023. And the number of adults using e-cigarettes is increasing, according to the US CDC. In 2023, 6.5% of adults over age 18 used e-cigarettes, up from 3.7% in 2020. 

Ohrin and colleagues conducted a cross-sectional analysis of adults enrolled in the National Institutes of Health All of Us Research Program. Participants self-reported e-cigarette use. PUD was defined using validated electronic health record diagnosis codes.

Among the 371,398 participants, 29,373 (8%) reported using e-cigarettes, including 21,277 current users and 8096 former users. E-cigarette users were significantly younger (mean age 45.3 vs 59.3 years; P < .001), more likely to be female, and more likely to report lower education and income (P < .001). 

Current e-cigarette users had 27% higher odds of PUD (adjusted odds ratio [aOR], 1.27; 95% CI, 1.12-1.45), compared to never-users. This was greater than the risk with traditional combustible cigarettes (aOR, 1.19) that was seen in the study.

Former e-cig users had 13% higher odds (aOR, 1.13; 95% CI, 1.04-1.24) compared to never-users, and any e-cigarette use was associated with higher odds of PUD (aOR, 1.17; 95% CI, 1.09-1.26) compared to never-use. 

Use of non-steroidal anti-inflammatories (aOR, 2.15) and having gastroesophageal reflux disease (aOR, 4.45) presented the most significant PUD risk.

Ohrin said he and his colleagues were surprised to see that people who had stopped using e-cigarettes still had higher odds of PUD, although he pointed out that the researchers did not know the frequency of use or how long users had stopped. 

“Now that we know there’s an association, we are going to do more studies on e-cigarettes” to see what the potential harms are, especially on the gastrointestinal system, he told GI & Hepatology News. 

“One of the things we are looking to elicit is — is there a dose response?” he said, noting it would take a prospective trial to determine that effect.

 

‘Opens a Door’ to Looking at the GI System

Laura Crotty Alexander, MD, a professor of medicine and associate division chief of pulmonary, critical care, sleep medicine, and physiology at the University of California, San Diego, said she found the study novel and interesting. 

“It’s the first I’ve heard of an association between e-cigarette vaping and peptic ulcer disease,” said Crotty Alexander, who has studied the health effects of e-cigarettes for a decade. 

Previous studies have shown that nicotine itself can drive an increase in gastric acid production and decrease healing, which can contribute to PUD, Crotty Alexander told GI & Hepatology News. With combustible cigarettes, it is thought that “the larger drivers of that association are the other things in tobacco smoke, such as tar and carbon monoxide and a million other horrible chemicals,” she said. 

Crotty Alexander and her colleagues have conducted studies in vitro and in mice that show that e-cigarette aerosols are irritants and cause oxidative stress, which can drive PUD. 

While many studies have shown vaping impacts various organs, Ohrin’s study “opens a door” to start looking at the gastrointestinal system, she said. 

The study is also a signal to clinicians to “take an accurate inhalant history,” which means asking about vaping, she added.

Ohrin and Crotty Alexander reported no conflicts.

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

PHOENIX — Users of e-cigarettes had increased odds of peptic ulcer disease (PUD) compared to those who have never used them, a cross-sectional study found.

The study also found increased risk of PUD among former users of e-cigarettes, reported Albert E. Ohrin, MBChB, MHS, of Ascension Saint Agnes Hospital, Baltimore, Maryland, who presented the study here at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting. 

While cigarette smoking is a known risk factor for PUD, there was little in the literature investigating whether vaping has a similar risk profile, said Ohrin, a first-year internal medicine resident. He told GI & Hepatology News he found e-cigarette users on Reddit discussing worsening PUD and decided to investigate further, especially since vaping is so popular among young people.

E-cigarettes are the most-used tobacco product among middle and high school students. The National Youth Tobacco Survey in the US reported that 1.6 million students (5.9%) vaped in 2024, a decline from 7.7% in 2023. And the number of adults using e-cigarettes is increasing, according to the US CDC. In 2023, 6.5% of adults over age 18 used e-cigarettes, up from 3.7% in 2020. 

Ohrin and colleagues conducted a cross-sectional analysis of adults enrolled in the National Institutes of Health All of Us Research Program. Participants self-reported e-cigarette use. PUD was defined using validated electronic health record diagnosis codes.

Among the 371,398 participants, 29,373 (8%) reported using e-cigarettes, including 21,277 current users and 8096 former users. E-cigarette users were significantly younger (mean age 45.3 vs 59.3 years; P < .001), more likely to be female, and more likely to report lower education and income (P < .001). 

Current e-cigarette users had 27% higher odds of PUD (adjusted odds ratio [aOR], 1.27; 95% CI, 1.12-1.45), compared to never-users. This was greater than the risk with traditional combustible cigarettes (aOR, 1.19) that was seen in the study.

Former e-cig users had 13% higher odds (aOR, 1.13; 95% CI, 1.04-1.24) compared to never-users, and any e-cigarette use was associated with higher odds of PUD (aOR, 1.17; 95% CI, 1.09-1.26) compared to never-use. 

Use of non-steroidal anti-inflammatories (aOR, 2.15) and having gastroesophageal reflux disease (aOR, 4.45) presented the most significant PUD risk.

Ohrin said he and his colleagues were surprised to see that people who had stopped using e-cigarettes still had higher odds of PUD, although he pointed out that the researchers did not know the frequency of use or how long users had stopped. 

“Now that we know there’s an association, we are going to do more studies on e-cigarettes” to see what the potential harms are, especially on the gastrointestinal system, he told GI & Hepatology News. 

“One of the things we are looking to elicit is — is there a dose response?” he said, noting it would take a prospective trial to determine that effect.

 

‘Opens a Door’ to Looking at the GI System

Laura Crotty Alexander, MD, a professor of medicine and associate division chief of pulmonary, critical care, sleep medicine, and physiology at the University of California, San Diego, said she found the study novel and interesting. 

“It’s the first I’ve heard of an association between e-cigarette vaping and peptic ulcer disease,” said Crotty Alexander, who has studied the health effects of e-cigarettes for a decade. 

Previous studies have shown that nicotine itself can drive an increase in gastric acid production and decrease healing, which can contribute to PUD, Crotty Alexander told GI & Hepatology News. With combustible cigarettes, it is thought that “the larger drivers of that association are the other things in tobacco smoke, such as tar and carbon monoxide and a million other horrible chemicals,” she said. 

Crotty Alexander and her colleagues have conducted studies in vitro and in mice that show that e-cigarette aerosols are irritants and cause oxidative stress, which can drive PUD. 

While many studies have shown vaping impacts various organs, Ohrin’s study “opens a door” to start looking at the gastrointestinal system, she said. 

The study is also a signal to clinicians to “take an accurate inhalant history,” which means asking about vaping, she added.

Ohrin and Crotty Alexander reported no conflicts.

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

PHOENIX — Users of e-cigarettes had increased odds of peptic ulcer disease (PUD) compared to those who have never used them, a cross-sectional study found.

The study also found increased risk of PUD among former users of e-cigarettes, reported Albert E. Ohrin, MBChB, MHS, of Ascension Saint Agnes Hospital, Baltimore, Maryland, who presented the study here at the American College of Gastroenterology (ACG) 2025 Annual Scientific Meeting. 

While cigarette smoking is a known risk factor for PUD, there was little in the literature investigating whether vaping has a similar risk profile, said Ohrin, a first-year internal medicine resident. He told GI & Hepatology News he found e-cigarette users on Reddit discussing worsening PUD and decided to investigate further, especially since vaping is so popular among young people.

E-cigarettes are the most-used tobacco product among middle and high school students. The National Youth Tobacco Survey in the US reported that 1.6 million students (5.9%) vaped in 2024, a decline from 7.7% in 2023. And the number of adults using e-cigarettes is increasing, according to the US CDC. In 2023, 6.5% of adults over age 18 used e-cigarettes, up from 3.7% in 2020. 

Ohrin and colleagues conducted a cross-sectional analysis of adults enrolled in the National Institutes of Health All of Us Research Program. Participants self-reported e-cigarette use. PUD was defined using validated electronic health record diagnosis codes.

Among the 371,398 participants, 29,373 (8%) reported using e-cigarettes, including 21,277 current users and 8096 former users. E-cigarette users were significantly younger (mean age 45.3 vs 59.3 years; P < .001), more likely to be female, and more likely to report lower education and income (P < .001). 

Current e-cigarette users had 27% higher odds of PUD (adjusted odds ratio [aOR], 1.27; 95% CI, 1.12-1.45), compared to never-users. This was greater than the risk with traditional combustible cigarettes (aOR, 1.19) that was seen in the study.

Former e-cig users had 13% higher odds (aOR, 1.13; 95% CI, 1.04-1.24) compared to never-users, and any e-cigarette use was associated with higher odds of PUD (aOR, 1.17; 95% CI, 1.09-1.26) compared to never-use. 

Use of non-steroidal anti-inflammatories (aOR, 2.15) and having gastroesophageal reflux disease (aOR, 4.45) presented the most significant PUD risk.

Ohrin said he and his colleagues were surprised to see that people who had stopped using e-cigarettes still had higher odds of PUD, although he pointed out that the researchers did not know the frequency of use or how long users had stopped. 

“Now that we know there’s an association, we are going to do more studies on e-cigarettes” to see what the potential harms are, especially on the gastrointestinal system, he told GI & Hepatology News. 

“One of the things we are looking to elicit is — is there a dose response?” he said, noting it would take a prospective trial to determine that effect.

 

‘Opens a Door’ to Looking at the GI System

Laura Crotty Alexander, MD, a professor of medicine and associate division chief of pulmonary, critical care, sleep medicine, and physiology at the University of California, San Diego, said she found the study novel and interesting. 

“It’s the first I’ve heard of an association between e-cigarette vaping and peptic ulcer disease,” said Crotty Alexander, who has studied the health effects of e-cigarettes for a decade. 

Previous studies have shown that nicotine itself can drive an increase in gastric acid production and decrease healing, which can contribute to PUD, Crotty Alexander told GI & Hepatology News. With combustible cigarettes, it is thought that “the larger drivers of that association are the other things in tobacco smoke, such as tar and carbon monoxide and a million other horrible chemicals,” she said. 

Crotty Alexander and her colleagues have conducted studies in vitro and in mice that show that e-cigarette aerosols are irritants and cause oxidative stress, which can drive PUD. 

While many studies have shown vaping impacts various organs, Ohrin’s study “opens a door” to start looking at the gastrointestinal system, she said. 

The study is also a signal to clinicians to “take an accurate inhalant history,” which means asking about vaping, she added.

Ohrin and Crotty Alexander reported no conflicts.

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

Oral induction therapy with obefazimod (Abivax) for 8 weeks led to clinically meaningful improvements across all efficacy endpoints in a highly refractory population of patients with moderately to severely active ulcerative colitis (UC).

The findings, from the ABTECT-1 and ABTECT-2 phase 3 induction trials, were presented in two separate late-breaking presentations at United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

“These trials enrolled a broad spectrum of participants, including one of the most severe and refractory populations evaluated to date in a phase 3 UC trial, with about 60% of patients across the pooled dataset having a Mayo endoscopic subscore of 3 — the highest level of UC endoscopic disease activity,” study investigator Marla Dubinsky, MD, gastroenterologist and co-director of the IBD Center at Mount Sinai in New York City, told GI & Hepatology News.

“Even within this challenging population, obefazimod achieved the primary endpoint of clinical remission and all key secondary endpoints, including endoscopic improvement, after just 8 weeks of therapy,” Dubinsky said.

This suggests that obefazimod may serve as both an early advanced therapy option and a much-needed alternative for patients with moderately to severely active UC who have failed multiple biologics and JAK inhibitors, with few choices left short of colectomy, she added.

 

Study Details

Obefazimod is an investigational oral, potentially first-in-class drug that enhances expression of microRNA-124, resulting in regulation of the inflammatory response and restoring mucosal homeostasis in UC.

The ABTECT-1 and ABTECT-2 were identically designed induction trials enrolling a total of 1272 patients with moderately to severely active UC who had inadequate response, loss of response, or intolerance to at least one prior therapy (with no upper limit), including corticosteroids, immunosuppressants, biologics, S1P receptor modulators, and/or JAK inhibitors. Participants were randomly assigned in a 2:1:1 ratio to receive obefazimod 50 mg or 25 mg or placebo once daily for 8 weeks.

In ABTECT-1, obefazimod 50 mg and 25 mg met the primary endpoint of clinical remission, with 22% of patients in the 50-mg group and 24% in the 25-mg group achieving clinical remission at 8 weeks compared with 2.5% of the placebo group.

The effect sizes for clinical remission were 21% for the 25-mg dose and 19% for the 50-mg dose, reported Bruce E. Sands, MD, MS, AGAF, professor of medicine at Icahn School of Medicine at Mount Sinai and chief in the Division of Gastroenterology at Mount Sinai Health System in New York City.

In ABTECT-2, the 50-mg dose met the primary endpoint of clinical remission, with 20% of patients achieving remission compared with 11% in the 25-mg group and 6.3% in the placebo group.

The effect sizes for clinical remission in ABTECT-2 were “a bit smaller” (13% for the 50-mg dose and 5% for the 25-mg dose) “because the absolute efficacy of 50 mg in this study was a little bit lower, and the placebo response rate was a little bit higher at 6.3%, and so accordingly, the 25-mg dose did not achieve statistical significance,” Sands explained.

Both doses of obefazimod met all secondary endpoints in ABTECT-1 and the 50-mg dose achieved all secondary endpoints in ABTECT-2. Secondary endpoints included clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement.

Pooled data across the two studies showed that both doses achieved “clinically meaningful improvements across all efficacy points,” Sands noted.

Notably, obefazimod 50 mg once daily achieved “consistent and clinically meaningful improvements” regardless of prior failure of advanced therapy, and both doses performed similarly well in the subgroup with no prior failure of advanced therapy, Silvio Danese, MD, PhD, with Vita-Salute San Raffaele University, Milan, Italy, reported in a separate presentation.

 

Adverse Events ‘Not a Barrier to Treatment’

Pooled data across the two studies showed no signal for serious, severe, or opportunistic infections or malignancies.

The most commonly reported treatment-emergent adverse event was headache, reported in 24% and 16% of patients taking obefazimod 50 mg and 25 mg, respectively, vs 6% of those taking placebo. Headaches were mild, transient, and short-lasting and “not a barrier to treatment, as evidenced by the low discontinuation (< 1%),” Sands noted.

“Because this is a safe agent and it’s an oral agent and convenient, I think the drug could be used early in the course of the disease, before advanced therapy or after failure of advanced therapies, even multiple advanced therapies,” Sands said.

“Of course, we’ll have to see what the maintenance data show. But we have a long experience from the phase 2a and 2b long-term extension treatments, and the durability seems to be quite good,” Sands cautioned.

Abivax CEO Marc de Garidel, MBA, told GI & Hepatology News that the company will share “top-line data” from the 44-week maintenance study evaluating obefazimod in UC in the second quarter of 2026.

“If positive, the data will support a potential NDA [New Drug Application] submission in the second half of 2026,” de Garidel said.

 

‘Promising Data’

Ashwin Ananthakrishnan, MBBS, MPH, AGAF, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, Boston, who wasn’t involved in the study, was impressed.

“I think this is very promising data from an important study. This is an entirely novel mechanism of action in ulcerative colitis,” Ananthakrishnan told GI & Hepatology News.

“While we have many treatments available, there are still a large number of patients who do not respond to existing treatment mechanisms,” he said. These trials “consisted of a large number of very refractory patients (severe endoscopic disease or multiple prior mechanism failures). That it works well in this population is very promising (and clinically impactful).”

It would be a “welcome addition to the armamentarium,” he added.

The study was funded by Abivax. Several study authors disclosed having financial relationships with the company. Ananthakrishnan reported having no disclosures.

 

A version of this article appeared on Medscape.com.

Oral induction therapy with obefazimod (Abivax) for 8 weeks led to clinically meaningful improvements across all efficacy endpoints in a highly refractory population of patients with moderately to severely active ulcerative colitis (UC).

The findings, from the ABTECT-1 and ABTECT-2 phase 3 induction trials, were presented in two separate late-breaking presentations at United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

“These trials enrolled a broad spectrum of participants, including one of the most severe and refractory populations evaluated to date in a phase 3 UC trial, with about 60% of patients across the pooled dataset having a Mayo endoscopic subscore of 3 — the highest level of UC endoscopic disease activity,” study investigator Marla Dubinsky, MD, gastroenterologist and co-director of the IBD Center at Mount Sinai in New York City, told GI & Hepatology News.

“Even within this challenging population, obefazimod achieved the primary endpoint of clinical remission and all key secondary endpoints, including endoscopic improvement, after just 8 weeks of therapy,” Dubinsky said.

This suggests that obefazimod may serve as both an early advanced therapy option and a much-needed alternative for patients with moderately to severely active UC who have failed multiple biologics and JAK inhibitors, with few choices left short of colectomy, she added.

 

Study Details

Obefazimod is an investigational oral, potentially first-in-class drug that enhances expression of microRNA-124, resulting in regulation of the inflammatory response and restoring mucosal homeostasis in UC.

The ABTECT-1 and ABTECT-2 were identically designed induction trials enrolling a total of 1272 patients with moderately to severely active UC who had inadequate response, loss of response, or intolerance to at least one prior therapy (with no upper limit), including corticosteroids, immunosuppressants, biologics, S1P receptor modulators, and/or JAK inhibitors. Participants were randomly assigned in a 2:1:1 ratio to receive obefazimod 50 mg or 25 mg or placebo once daily for 8 weeks.

In ABTECT-1, obefazimod 50 mg and 25 mg met the primary endpoint of clinical remission, with 22% of patients in the 50-mg group and 24% in the 25-mg group achieving clinical remission at 8 weeks compared with 2.5% of the placebo group.

The effect sizes for clinical remission were 21% for the 25-mg dose and 19% for the 50-mg dose, reported Bruce E. Sands, MD, MS, AGAF, professor of medicine at Icahn School of Medicine at Mount Sinai and chief in the Division of Gastroenterology at Mount Sinai Health System in New York City.

In ABTECT-2, the 50-mg dose met the primary endpoint of clinical remission, with 20% of patients achieving remission compared with 11% in the 25-mg group and 6.3% in the placebo group.

The effect sizes for clinical remission in ABTECT-2 were “a bit smaller” (13% for the 50-mg dose and 5% for the 25-mg dose) “because the absolute efficacy of 50 mg in this study was a little bit lower, and the placebo response rate was a little bit higher at 6.3%, and so accordingly, the 25-mg dose did not achieve statistical significance,” Sands explained.

Both doses of obefazimod met all secondary endpoints in ABTECT-1 and the 50-mg dose achieved all secondary endpoints in ABTECT-2. Secondary endpoints included clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement.

Pooled data across the two studies showed that both doses achieved “clinically meaningful improvements across all efficacy points,” Sands noted.

Notably, obefazimod 50 mg once daily achieved “consistent and clinically meaningful improvements” regardless of prior failure of advanced therapy, and both doses performed similarly well in the subgroup with no prior failure of advanced therapy, Silvio Danese, MD, PhD, with Vita-Salute San Raffaele University, Milan, Italy, reported in a separate presentation.

 

Adverse Events ‘Not a Barrier to Treatment’

Pooled data across the two studies showed no signal for serious, severe, or opportunistic infections or malignancies.

The most commonly reported treatment-emergent adverse event was headache, reported in 24% and 16% of patients taking obefazimod 50 mg and 25 mg, respectively, vs 6% of those taking placebo. Headaches were mild, transient, and short-lasting and “not a barrier to treatment, as evidenced by the low discontinuation (< 1%),” Sands noted.

“Because this is a safe agent and it’s an oral agent and convenient, I think the drug could be used early in the course of the disease, before advanced therapy or after failure of advanced therapies, even multiple advanced therapies,” Sands said.

“Of course, we’ll have to see what the maintenance data show. But we have a long experience from the phase 2a and 2b long-term extension treatments, and the durability seems to be quite good,” Sands cautioned.

Abivax CEO Marc de Garidel, MBA, told GI & Hepatology News that the company will share “top-line data” from the 44-week maintenance study evaluating obefazimod in UC in the second quarter of 2026.

“If positive, the data will support a potential NDA [New Drug Application] submission in the second half of 2026,” de Garidel said.

 

‘Promising Data’

Ashwin Ananthakrishnan, MBBS, MPH, AGAF, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, Boston, who wasn’t involved in the study, was impressed.

“I think this is very promising data from an important study. This is an entirely novel mechanism of action in ulcerative colitis,” Ananthakrishnan told GI & Hepatology News.

“While we have many treatments available, there are still a large number of patients who do not respond to existing treatment mechanisms,” he said. These trials “consisted of a large number of very refractory patients (severe endoscopic disease or multiple prior mechanism failures). That it works well in this population is very promising (and clinically impactful).”

It would be a “welcome addition to the armamentarium,” he added.

The study was funded by Abivax. Several study authors disclosed having financial relationships with the company. Ananthakrishnan reported having no disclosures.

 

A version of this article appeared on Medscape.com.

Oral induction therapy with obefazimod (Abivax) for 8 weeks led to clinically meaningful improvements across all efficacy endpoints in a highly refractory population of patients with moderately to severely active ulcerative colitis (UC).

The findings, from the ABTECT-1 and ABTECT-2 phase 3 induction trials, were presented in two separate late-breaking presentations at United European Gastroenterology (UEG) Week 2025 in Berlin, Germany.

“These trials enrolled a broad spectrum of participants, including one of the most severe and refractory populations evaluated to date in a phase 3 UC trial, with about 60% of patients across the pooled dataset having a Mayo endoscopic subscore of 3 — the highest level of UC endoscopic disease activity,” study investigator Marla Dubinsky, MD, gastroenterologist and co-director of the IBD Center at Mount Sinai in New York City, told GI & Hepatology News.

“Even within this challenging population, obefazimod achieved the primary endpoint of clinical remission and all key secondary endpoints, including endoscopic improvement, after just 8 weeks of therapy,” Dubinsky said.

This suggests that obefazimod may serve as both an early advanced therapy option and a much-needed alternative for patients with moderately to severely active UC who have failed multiple biologics and JAK inhibitors, with few choices left short of colectomy, she added.

 

Study Details

Obefazimod is an investigational oral, potentially first-in-class drug that enhances expression of microRNA-124, resulting in regulation of the inflammatory response and restoring mucosal homeostasis in UC.

The ABTECT-1 and ABTECT-2 were identically designed induction trials enrolling a total of 1272 patients with moderately to severely active UC who had inadequate response, loss of response, or intolerance to at least one prior therapy (with no upper limit), including corticosteroids, immunosuppressants, biologics, S1P receptor modulators, and/or JAK inhibitors. Participants were randomly assigned in a 2:1:1 ratio to receive obefazimod 50 mg or 25 mg or placebo once daily for 8 weeks.

In ABTECT-1, obefazimod 50 mg and 25 mg met the primary endpoint of clinical remission, with 22% of patients in the 50-mg group and 24% in the 25-mg group achieving clinical remission at 8 weeks compared with 2.5% of the placebo group.

The effect sizes for clinical remission were 21% for the 25-mg dose and 19% for the 50-mg dose, reported Bruce E. Sands, MD, MS, AGAF, professor of medicine at Icahn School of Medicine at Mount Sinai and chief in the Division of Gastroenterology at Mount Sinai Health System in New York City.

In ABTECT-2, the 50-mg dose met the primary endpoint of clinical remission, with 20% of patients achieving remission compared with 11% in the 25-mg group and 6.3% in the placebo group.

The effect sizes for clinical remission in ABTECT-2 were “a bit smaller” (13% for the 50-mg dose and 5% for the 25-mg dose) “because the absolute efficacy of 50 mg in this study was a little bit lower, and the placebo response rate was a little bit higher at 6.3%, and so accordingly, the 25-mg dose did not achieve statistical significance,” Sands explained.

Both doses of obefazimod met all secondary endpoints in ABTECT-1 and the 50-mg dose achieved all secondary endpoints in ABTECT-2. Secondary endpoints included clinical response, endoscopic improvement, symptomatic remission, and histo-endoscopic mucosal improvement.

Pooled data across the two studies showed that both doses achieved “clinically meaningful improvements across all efficacy points,” Sands noted.

Notably, obefazimod 50 mg once daily achieved “consistent and clinically meaningful improvements” regardless of prior failure of advanced therapy, and both doses performed similarly well in the subgroup with no prior failure of advanced therapy, Silvio Danese, MD, PhD, with Vita-Salute San Raffaele University, Milan, Italy, reported in a separate presentation.

 

Adverse Events ‘Not a Barrier to Treatment’

Pooled data across the two studies showed no signal for serious, severe, or opportunistic infections or malignancies.

The most commonly reported treatment-emergent adverse event was headache, reported in 24% and 16% of patients taking obefazimod 50 mg and 25 mg, respectively, vs 6% of those taking placebo. Headaches were mild, transient, and short-lasting and “not a barrier to treatment, as evidenced by the low discontinuation (< 1%),” Sands noted.

“Because this is a safe agent and it’s an oral agent and convenient, I think the drug could be used early in the course of the disease, before advanced therapy or after failure of advanced therapies, even multiple advanced therapies,” Sands said.

“Of course, we’ll have to see what the maintenance data show. But we have a long experience from the phase 2a and 2b long-term extension treatments, and the durability seems to be quite good,” Sands cautioned.

Abivax CEO Marc de Garidel, MBA, told GI & Hepatology News that the company will share “top-line data” from the 44-week maintenance study evaluating obefazimod in UC in the second quarter of 2026.

“If positive, the data will support a potential NDA [New Drug Application] submission in the second half of 2026,” de Garidel said.

 

‘Promising Data’

Ashwin Ananthakrishnan, MBBS, MPH, AGAF, associate professor of medicine at Harvard Medical School and a gastroenterologist at Massachusetts General Hospital, Boston, who wasn’t involved in the study, was impressed.

“I think this is very promising data from an important study. This is an entirely novel mechanism of action in ulcerative colitis,” Ananthakrishnan told GI & Hepatology News.

“While we have many treatments available, there are still a large number of patients who do not respond to existing treatment mechanisms,” he said. These trials “consisted of a large number of very refractory patients (severe endoscopic disease or multiple prior mechanism failures). That it works well in this population is very promising (and clinically impactful).”

It would be a “welcome addition to the armamentarium,” he added.

The study was funded by Abivax. Several study authors disclosed having financial relationships with the company. Ananthakrishnan reported having no 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.

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.

BERLIN — Pairing a screening or surveillance colonoscopy with a same-day esophagogastroduodenoscopy (EGD) proved feasible and yielded clinically relevant upper gastrointestinal (GI) findings, including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.

“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.

While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.

The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”

Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.

 

Mixed Rates of GI Cancers Across Europe and the US

These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.

However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”

The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy. 

A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.

Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.

 

Neoplasia and Preneoplasia Found

A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.

A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”

Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.

Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.

Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.

“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.

“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”

 

PROSPERO: Early Detection of Upper GI Conditions in a UK Population

Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”

“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.

“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”

Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”

TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.

Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.

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

BERLIN — Pairing a screening or surveillance colonoscopy with a same-day esophagogastroduodenoscopy (EGD) proved feasible and yielded clinically relevant upper gastrointestinal (GI) findings, including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.

“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.

While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.

The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”

Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.

 

Mixed Rates of GI Cancers Across Europe and the US

These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.

However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”

The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy. 

A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.

Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.

 

Neoplasia and Preneoplasia Found

A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.

A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”

Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.

Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.

Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.

“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.

“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”

 

PROSPERO: Early Detection of Upper GI Conditions in a UK Population

Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”

“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.

“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”

Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”

TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.

Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.

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

BERLIN — Pairing a screening or surveillance colonoscopy with a same-day esophagogastroduodenoscopy (EGD) proved feasible and yielded clinically relevant upper gastrointestinal (GI) findings, including malignancies and lesions requiring ongoing surveillance, according to an interim analysis from the TOGAS study.

“There was an abundance of benign but clinically relevant findings,” said lead investigator Jan Bornschein, MD, gastroenterologist at Oxford University Hospitals NHS Foundation Trust, Oxford, England, who presented the interim resuts of the study at United European Gastroenterology (UEG) Week 2025.

While the study found upper GI neoplasia in only 1.4% of participants, 17.8% of individuals were marked for upper GI endoscopic surveillance.

The results may inform how Europe develops gastric cancer prevention programs alongside those for colorectal cancer, said Bornschein. “If we can combine the upper GI endoscopy with other modalities [colonoscopy], the more likelihood there is that you can have a one-stop test package,” he said. “A combination, particularly for bowel and stomach, is more feasible and also more cost-effective. So far, the findings show that it’s definitely a strategy that, in my opinion, is worth implementing.”

Bornschein and the TOGAS study group hope that the combined approach will prove workable across diverse European settings and will help identify a spectrum of upper GI pathology, from cancers and dysplasia to atrophy and intestinal metaplasia, that can meaningfully affect follow-up surveillance.

 

Mixed Rates of GI Cancers Across Europe and the US

These findings come amid data showing rising rates of early-onset (younger than 50 years) GI cancers in the US, including colorectal, gastric, pancreatic, and esophageal tumors. These trends, previously reported by this news organization, point to environmental and lifestyle drivers, strengthening the case for earlier detection and risk-tailored strategies for upper GI neoplasia and preneoplastic conditions detected during existing colorectal cancer screening pathways.

However, Bornschein noted that prevalence varies considerably across Europe. “There are areas, particularly in the Eastern regions, and in some parts of the West, for example, Portugal, that have a very high incidence of GI cancers. In the UK or in Germany, we have noticed a decline over the years, so the numbers are actually much better than they used to be.”

The study is the second in a series of three TOGAS pilot studies and was conducted across eight centers (France, Germany, Ireland, Latvia, Lithuania, the Netherlands, Portugal, and Spain) in adults aged 50-74 years attending screening or polyp-surveillance colonoscopy. 

A European Society of Gastrointestinal Endoscopy-aligned protocol defining image documentation, biopsy sampling, and quality parameters was followed to ensure a standardized approach. “Marked preneoplastic change” was defined as gastric glandular atrophy or intestinal metaplasia at the Operative Link on Gastritis Assessment/Operative Link on Gastric Intestinal Metaplasia Assessment stage III-IV and/or Endoscopic Grading of Gastric Intestinal Metaplasia > 5, triggering a need for endoscopic surveillance.

Data were gathered on colonoscopy findings (including polyp surveillance and family history), EGD findings plus biopsies, serum pepsinogen, and Helicobacter pylori serology. Outcome measures included the prevalence of gastric cancer and preneoplastic conditions, the diagnostic accuracy of pepsinogen testing, comparisons between national settings, the relevance of upper endoscopy in fecal immunochemical test-positive cases, and overall H pylori prevalence.

 

Neoplasia and Preneoplasia Found

A total of 846 participants were analyzed. At baseline, the mean age was 62 years, 52.2% were men, and 84.2% were White, despite efforts to recruit a more diverse population. Around 390 participants drank alcohol, and 190 smoked tobacco.

A total of 37.8% of participants had undergone prior EGD, of which 94.7% were performed more than 3 years before the study start. The history of GI surgery was 13.7%, and the history of cancer was 14.5%. Around 11% took aspirin, and 14% took proton pump inhibitors (PPIs). “We were surprised at the low prevalence of PPI use,” remarked Bornschein. “It was also good news that around half were never smokers.”

Key results for upper GI neoplasia included six patients (0.7%) with gastric cancers, three (0.4%) with esophageal cancers, and five (0.6%) with duodenal tumors. H pylori positivity was found in 303 patients (35.8%), with an additional 81 (9.6%) reporting a history of eradication.

Colorectal findings included 15 patients (1.8%) with cancers and colon polyps in 503 (59.5%) participants.

Regarding preneoplastic conditions, endoscopy identified intestinal metaplasia in 174 patients (20.6%), of which 65 (7.7%) were multifocal. Atrophy was observed in 220 patients (26.0%), with 59 (7.0%) showing multifocal atrophic changes. Both intestinal metaplasia and atrophy were found together in 105 (12.4%) patients. Barrett’s esophagus was detected in 31 (3.7%) patients.

“I’d really like to highlight these further benign gastric findings,” said Bornschein. These included gastric ulcers in 28 (3.3%) patients, erosive gastritis in 245 (29.0%) patients, esophageal ulcers in three (0.4%) patients, Los Angeles Community College District classification esophagitis in 13 (1.5%) patients, and duodenal ulcers in 10 (1.2%) patients. “These were asymptomatic, but we were able to identify them,” he noted.

“We’ve had a very low rate of complications (0.01%),” he added.” I don’t want to jinx that now. These were basically related to sedation.”

 

PROSPERO: Early Detection of Upper GI Conditions in a UK Population

Massimiliano di Pietro, MD, consultant gastroenterologist at Addenbrooke’s Hospital, Cambridge, England, and the principal investigator of the PROSPERO study, which aimed to determine the prevalence of premalignant upper GI conditions in routine endoscopy in the UK, commented on the findings. The TOGAS study focuses on asymptomatic individuals referred for colonoscopy and examines the value of performing an upper GI endoscopy at the same time, he explained. “This approach might identify upper GI conditions that require monitoring, in particular early cancer.”

“On the other hand, the PROSPERO study focuses on patients referred for upper GI symptoms and diagnosis,” he said. Preliminary data from that study, presented during the same session as the TOGAS trial, showed a 13.6% prevalence of premalignant upper GI conditions in a symptomatic UK patient population referred for endoscopy.

“In some respects, the findings were similar, particularly the rate of upper GI cancer at 1.4%, although there were differences in the prevalence of premalignant conditions,” he noted. “This may be explained by the fact that TOGAS is a European study, while PROSPERO is UK-based, where the distribution of upper GI cancers differs, with more esophageal adenocarcinoma vs gastric adenocarcinoma.”

Reflecting on both of the studies, Di Pietro said they are “really important in fulfilling an unmet need in the quality of upper GI endoscopy. Currently, there are no diagnostic quality indicators in upper GI endoscopy, so it’s difficult to rate the performance of endoscopists in the same way as we can in lower GI. It’s really important to understand the population prevalence, both in symptomatic and asymptomatic individuals, of premalignant and malignant upper GI conditions.”

TOGAS 2 is recruiting until February 2026, with 1200 of a potential 1600 participants recruited to date. The data will be used for implementation modeling and to inform quality indicators for future screening programs. Final results and plans for a follow-up study are expected in 2026.

Bornschein declared receiving advisory and speaker fees from Flynn Pharma and Juvisé Pharmaceuticals. Di Pietro reported having no disclosures relevant to the studies discussed.

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

VIENNA –Replacing the term nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD) has several important “pros” and “some minor cons,” Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees at United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.

In her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.

Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.

However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.

“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.

 

MASLD, MetALD, or ALD?

“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol? 

If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.

Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.

Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.

“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”

Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”

On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”

Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.

 

Cancer, Cirrhosis, CVD

MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.

In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.

Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.” 

One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”

During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”

Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”

 

Remaining Questions

And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”

The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.

No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.

 

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

VIENNA –Replacing the term nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD) has several important “pros” and “some minor cons,” Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees at United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.

In her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.

Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.

However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.

“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.

 

MASLD, MetALD, or ALD?

“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol? 

If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.

Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.

Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.

“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”

Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”

On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”

Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.

 

Cancer, Cirrhosis, CVD

MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.

In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.

Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.” 

One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”

During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”

Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”

 

Remaining Questions

And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”

The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.

No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.

 

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

VIENNA –Replacing the term nonalcoholic fatty liver disease (NAFLD) with metabolic dysfunction-associated steatotic liver disease (MASLD) has several important “pros” and “some minor cons,” Maria Effenberger, MD, Medical University of Innsbruck, Berlin, Germany, told attendees at United European Gastroenterology (UEG) Week 2025 in Vienna, Austria.

In her presentation, “Sense and Nonsense of the New Nomenclature,” Effenberger highlighted the clinical implications of the new liver-disease terminology and pointed to a few factors still needing to be sorted out.

Both NAFLD and MASLD are steatotic liver diseasesand, notably, there are few differences between the two in clinical studies, which makes the terminology shift easier, said Effenberger. She cited a recent study showing demographic and clinical profiles of individuals classified as NAFLD and MASLD in the US were “strikingly similar,” as were the accuracy of the noninvasive tests and all-cause and cause-specific mortality rates for both conditions.

However, “the important thing about MASLD is that the term is really connected to metabolic dysfunction,” said Effenberger. To be diagnosed with MASLD, patients with liver disease need to have at least one of five cardiometabolic abnormalities: a high BMI — over 25 in White people and over 23 in Asian people; type 2 diabetes (T2D) or prediabetes; arterial hypertension; high levels of triglycerides; or a low level of high-density lipoprotein cholesterol.

“MASLD is a systemic disease, and that term represents it much better than only looking at it as a hepatological disease,” Effenberger said. “Many factors, especially inflammatory ones, influence steatosis, inflammation, and fibrosis.” These include influences from adipose tissue, the gut microbiome, the brain, a hypocaloric diet, and from steatosis of the liver itself. Proinflammatory cytokines induced by the disease can lead to inflammation throughout the body, with clinical outcomes such as stroke, heart failure, arrhythmias, myocardial infarction, chronic kidney disease.

 

MASLD, MetALD, or ALD?

“What is important now,” said Effenberger, is that “every patient who has liver disease should be asked two questions.” The first question is whether the patient has any of the cardiometabolic criteria outlined above. Second, is the patient consuming alcohol? 

If the patient has one of the cardiometabolic criteria but doesn’t consume alcohol, “we are straight at the diagnosis of MASLD,” she explained. If the patient does consume alcohol, it depends on how much.

Patients who have at least one cardiometabolic risk factor and consume 140-350 g for men and 210-420 g for women are considered to have Metabolic and Alcohol-Associated Liver Disease (MetALD). And those with steatotic liver disease who drink alcohol above the MetALD thresholds are considered to have ALD.

Effenberger pointed to two “cons” of the new nomenclature that need to be clarified. Although MetALD has poorer outcomes than MASLD, “it’s really hard to differentiate between ALD and MASLD,” she said. Yet the distinction is important because risks for cirrhosis, hepatocellular carcinoma (HCC), and overall mortality increase more for patients diagnosed with ALD vs MASLD.

“Do MASLD patients drink alcohol? Yes they do,” Effenberger said. “And if you have MASLD and another trigger factor like alcohol, the rates of mortality, morbidity and cancer go up.”

Moderator Laurent Castera, MD, PhD, Université Paris-Cité, Paris, France, noted that a “pro” of the new nomenclature is that it is “shedding light on the importance of alcohol because when we discuss steatotic liver disease or MASLD, alcohol is always the elephant in the room,” he said. “We need to increase the awareness that even in the absence of alcohol, you can still develop cirrhosis if you have severe metabolic risk factors.”

On the other hand, he said, “We desperately need more statistics on the true prevalence of alcohol consumption. While studies suggest the prevalence is low, at around 4% or 5%, that does not match the reality, in my opinion.”

Effenberger agreed. There’s a problem in trying to zero in on alcohol consumption because of the stigma attached to it, she said. She pointed to an Austrian study assessing patients who are diagnosed with MASLD. The researchers asked them, “Do you drink alcohol?” and all the participants said “no.” However, after completing a questionnaire designed to identify alcohol use disorders, and undergoing glucuronide tests in the urine and hair, it became clear that 25%-30% of these patients actually drank alcohol on a regular basis.

 

Cancer, Cirrhosis, CVD

MASLD is a trigger for cancer, especially HCC, Effenberger said. A recent review affirmed that MASLD is strongly associated with HCC, especially in Southeast Asia and India. The same study showed that many patients with MASLD are getting HCC without cirrhosis, and their cancer is often detected at a later stage, however, it’s not yet clear why they are getting HCC, and further study is needed.

In addition, MASLD is also associated with higher rates of extrahepatic cancers, including cancers of the skin and androgenic cancers. This, too, requires further investigation.

Regarding cardiovascular disease (CVD) risk, Effenberger emphasized that cardiometabolic diseases are strongly linked to each other. “Therefore, if you have diabetes and MASLD, the rates of atherosclerosis and of heart insufficiency and arteriosclerotic events like stroke and heart attacks go up, leading to the question of whether a CVD risk assessment is necessary in patients with MASLD.” 

One recent study suggests that yes, it is, she reported. “If a patient has MASLD and cardiometabolic risk factors, and a risk score that suggests the patient is at increased risk of CVD for 10 years, then a CT scan of the arteries of the heart is important. The increased risk could also lead to intensified medical therapy, including GLP-1s or SGLT2s.”

During the Q&A, one attendee asked whether all patients with noncirrhotic MASLD should be screened for HCC, given the increased risk. Effenberger agreed that would be the best way to identify those at high risk; however, she said, “I think science is not in a state where you can clearly define which patients will be at high risk, and so we don’t have any guidelines for that.”

Another attendee asked why HCC is more common in Indians and Asians. Effenberger said, “We don’t know, but it is likely that there is an HCC-driven genetic risk factor.”

 

Remaining Questions

And finally, there’s the question of “what do we do with burnt-out MASLD?” Effenberger asked. “We know the fat content of the liver decreases when liver severity goes up. Therefore, we have a lot of patients with cirrhosis whose disease is not defined as steatotic liver because the liver fat content is no longer more than 5%.”

The decrease in fat is an ongoing process, and therefore, these patients with MASLD and advanced hepatic disease need to be better represented in the nomenclature, she suggested.

No funding information was provided. Effenberger declared working with Ipsen as a potential conflict.

 

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