From the Journals

The prevalence of eosinophilic esophagitis (EoE) has increased fivefold in the United States since 2009, now affecting about 1 in 700 people and totaling $1.32 billion in annual healthcare costs, according to recent research.

Although EoE has been considered a rare disease, the chronic condition is becoming more common, and healthcare providers should expect to encounter EoE in clinical settings, the study authors wrote.

“Our last assessment of the prevalence and burden of EoE was more than 10 years ago, and we had a strong suspicion we would continue to see increased numbers of patients with EoE and an increasing cost burden related to the condition in the United States,” said senior author Evan S. Dellon, MD, MPH, AGAF, professor of gastroenterology and hepatology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine, Chapel Hill, North Carolina.

“EoE is becoming more common,” Dellon said. “Healthcare providers should expect to see EoE in their practices, including in the primary care setting, emergency departments, allergy practices, GI [gastrointestinal] practices, ENT clinics, and endoscopy suites.”

The study was published in Clinical Gastroenterology and Hepatology.

Estimating EoE Prevalence

Dellon and colleagues analyzed the Merative MarketScan Commercial Claims and Encounters and Medicare Fee-for-Service databases to calculate the annual prevalence of EoE, as well as age- and sex-stratified estimates standardized to the US population. They also calculated healthcare utilization, including medications and endoscopic procedures, to estimate annual EoE-associated costs. Since the EoE billing code was introduced in 2008, the analysis included 2009-2022 MarketScan and 2009-2017 Medicare data.

In the MarketScan database, the research team identified 20,435 EoE cases in 2022, with a mean age of 38 years, 16% younger than 18 years, 62% men, and 41% with a comorbid allergic disease code. The most common symptoms and diagnoses were dysphagia (39%), abdominal pain or dyspepsia (24%), and esophageal stricture (19%). Over time, patients also had previous codes for comorbid allergic diseases (64%), dysphagia (62%), or esophageal stricture (32%).

In the Medicare database, the research team identified 1913 EoE cases in 2017, with a mean age of 73 years, 47% men, 90% non-Hispanic White, and 36% with a comorbid allergic disease. The most common symptoms and diagnoses were dysphagia (49%), abdominal pain or dyspepsia (35%), and esophageal stricture (30%). Over time, patients also had codes for comorbid allergic diseases (64%), dysphagia (65%), or esophageal stricture (42%).

The database numbers translated to EoE prevalences of about 163 cases per 100,000 people in MarketScan in 2022 and 64 cases per 100,000 people in Medicare in 2017. Since 2009, there has been a fivefold increase in prevalence in both databases.

In MarketScan, the prevalence was higher among men than among women, at 204 vs 122 cases per 100,000 people. For both sexes, peak prevalence occurred between ages 40 and 44.

In Medicare, prevalence was also higher among men than among women, at 79 vs 55 cases per 100,000 people. Peak prevalence occurred between ages 65 and 69.

Standardized to the US population, EoE prevalence was 142.5 cases per 100,000 people, extrapolating to 472,380 cases. The overall prevalence was approximately 1 in 700, with rates of 1 in 617 for those younger than 65 years and 1 in 1562 for those aged ≥ 65 years.

“The rapidly increasing prevalence year over year for the entire timeframe of the study was surprising, as were our estimates of the total number of EoE patients in the US, which suggests that EoE is no longer a rare disease and is now seen in about 1 in 700 people,” Dellon said. “This almost triples our prior estimates of 1 in 2000 from 10 years ago, with all trends suggesting that the prevalence will continue to increase.”

 

Calculating EoE Costs

In terms of procedures, endoscopy with dilation or biopsy was used in about 60%-70% of patients with EoE in both MarketScan and Medicare during the years analyzed. In addition, upper endoscopy with biopsy was coded in 80%-90% of patients, guidewire-based dilation in 11%-17% of patients, and balloon-based dilation in 13%-20% of patients.

In terms of prescription medications, proton pump inhibitors (41%) and topical steroids (26%) were the most common in MarketScan in 2022, as well as in Medicare in 2017, at 32% and 9%, respectively.

When looking at costs by age and sex, the male cohort with the highest costs was aged 10-14 years, estimated at $106.7 million. Among the female cohort, the highest costs were associated with ages 15-19, estimated at $46.5 million.

Overall, total EoE-associated healthcare costs were estimated to be $1.04 billion in 2017, and when adjusted for inflation, the costs were estimated at $1.32 billion in 2024. This is likely an underestimate, the authors wrote, given that EoE prevalence has likely increased for ages 65 or older since 2017 and for all ages since 2022.

“Researching the prevalence and costs is essential to improving patient care by highlighting the growing burden of this recently recognized and growing chronic disease, guiding policy and insurer decisions, and advocating for better access to effective treatments and support for patients,” said Joy Chang, MD, assistant professor of medicine in the Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.Chang, who wasn’t involved with this study, specializes in eosinophilic GI diseases and researches patient-physician preferences and decision-making in EoE care.

“Clinicians should remain vigilant for symptoms, utilize guideline-based diagnostic approaches, and consider both medical and dietary treatment strategies to optimize patient outcomes and reduce long-term costs,” she said. “Increased awareness and timely intervention can help mitigate the growing impact of this chronic condition.”

The study was supported by a National Institutes of Health grant and used resources from the University of North Carolina Center for Gastrointestinal Biology and Disease. Dellon reported receiving research funding from and having consultant roles with numerous pharmaceutical companies and organizations. Chang reported having no relevant disclosures.

A version of this article appeared on Medscape.com.

The prevalence of eosinophilic esophagitis (EoE) has increased fivefold in the United States since 2009, now affecting about 1 in 700 people and totaling $1.32 billion in annual healthcare costs, according to recent research.

Although EoE has been considered a rare disease, the chronic condition is becoming more common, and healthcare providers should expect to encounter EoE in clinical settings, the study authors wrote.

“Our last assessment of the prevalence and burden of EoE was more than 10 years ago, and we had a strong suspicion we would continue to see increased numbers of patients with EoE and an increasing cost burden related to the condition in the United States,” said senior author Evan S. Dellon, MD, MPH, AGAF, professor of gastroenterology and hepatology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine, Chapel Hill, North Carolina.

“EoE is becoming more common,” Dellon said. “Healthcare providers should expect to see EoE in their practices, including in the primary care setting, emergency departments, allergy practices, GI [gastrointestinal] practices, ENT clinics, and endoscopy suites.”

The study was published in Clinical Gastroenterology and Hepatology.

Estimating EoE Prevalence

Dellon and colleagues analyzed the Merative MarketScan Commercial Claims and Encounters and Medicare Fee-for-Service databases to calculate the annual prevalence of EoE, as well as age- and sex-stratified estimates standardized to the US population. They also calculated healthcare utilization, including medications and endoscopic procedures, to estimate annual EoE-associated costs. Since the EoE billing code was introduced in 2008, the analysis included 2009-2022 MarketScan and 2009-2017 Medicare data.

In the MarketScan database, the research team identified 20,435 EoE cases in 2022, with a mean age of 38 years, 16% younger than 18 years, 62% men, and 41% with a comorbid allergic disease code. The most common symptoms and diagnoses were dysphagia (39%), abdominal pain or dyspepsia (24%), and esophageal stricture (19%). Over time, patients also had previous codes for comorbid allergic diseases (64%), dysphagia (62%), or esophageal stricture (32%).

In the Medicare database, the research team identified 1913 EoE cases in 2017, with a mean age of 73 years, 47% men, 90% non-Hispanic White, and 36% with a comorbid allergic disease. The most common symptoms and diagnoses were dysphagia (49%), abdominal pain or dyspepsia (35%), and esophageal stricture (30%). Over time, patients also had codes for comorbid allergic diseases (64%), dysphagia (65%), or esophageal stricture (42%).

The database numbers translated to EoE prevalences of about 163 cases per 100,000 people in MarketScan in 2022 and 64 cases per 100,000 people in Medicare in 2017. Since 2009, there has been a fivefold increase in prevalence in both databases.

In MarketScan, the prevalence was higher among men than among women, at 204 vs 122 cases per 100,000 people. For both sexes, peak prevalence occurred between ages 40 and 44.

In Medicare, prevalence was also higher among men than among women, at 79 vs 55 cases per 100,000 people. Peak prevalence occurred between ages 65 and 69.

Standardized to the US population, EoE prevalence was 142.5 cases per 100,000 people, extrapolating to 472,380 cases. The overall prevalence was approximately 1 in 700, with rates of 1 in 617 for those younger than 65 years and 1 in 1562 for those aged ≥ 65 years.

“The rapidly increasing prevalence year over year for the entire timeframe of the study was surprising, as were our estimates of the total number of EoE patients in the US, which suggests that EoE is no longer a rare disease and is now seen in about 1 in 700 people,” Dellon said. “This almost triples our prior estimates of 1 in 2000 from 10 years ago, with all trends suggesting that the prevalence will continue to increase.”

 

Calculating EoE Costs

In terms of procedures, endoscopy with dilation or biopsy was used in about 60%-70% of patients with EoE in both MarketScan and Medicare during the years analyzed. In addition, upper endoscopy with biopsy was coded in 80%-90% of patients, guidewire-based dilation in 11%-17% of patients, and balloon-based dilation in 13%-20% of patients.

In terms of prescription medications, proton pump inhibitors (41%) and topical steroids (26%) were the most common in MarketScan in 2022, as well as in Medicare in 2017, at 32% and 9%, respectively.

When looking at costs by age and sex, the male cohort with the highest costs was aged 10-14 years, estimated at $106.7 million. Among the female cohort, the highest costs were associated with ages 15-19, estimated at $46.5 million.

Overall, total EoE-associated healthcare costs were estimated to be $1.04 billion in 2017, and when adjusted for inflation, the costs were estimated at $1.32 billion in 2024. This is likely an underestimate, the authors wrote, given that EoE prevalence has likely increased for ages 65 or older since 2017 and for all ages since 2022.

“Researching the prevalence and costs is essential to improving patient care by highlighting the growing burden of this recently recognized and growing chronic disease, guiding policy and insurer decisions, and advocating for better access to effective treatments and support for patients,” said Joy Chang, MD, assistant professor of medicine in the Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.Chang, who wasn’t involved with this study, specializes in eosinophilic GI diseases and researches patient-physician preferences and decision-making in EoE care.

“Clinicians should remain vigilant for symptoms, utilize guideline-based diagnostic approaches, and consider both medical and dietary treatment strategies to optimize patient outcomes and reduce long-term costs,” she said. “Increased awareness and timely intervention can help mitigate the growing impact of this chronic condition.”

The study was supported by a National Institutes of Health grant and used resources from the University of North Carolina Center for Gastrointestinal Biology and Disease. Dellon reported receiving research funding from and having consultant roles with numerous pharmaceutical companies and organizations. Chang reported having no relevant disclosures.

A version of this article appeared on Medscape.com.

The prevalence of eosinophilic esophagitis (EoE) has increased fivefold in the United States since 2009, now affecting about 1 in 700 people and totaling $1.32 billion in annual healthcare costs, according to recent research.

Although EoE has been considered a rare disease, the chronic condition is becoming more common, and healthcare providers should expect to encounter EoE in clinical settings, the study authors wrote.

“Our last assessment of the prevalence and burden of EoE was more than 10 years ago, and we had a strong suspicion we would continue to see increased numbers of patients with EoE and an increasing cost burden related to the condition in the United States,” said senior author Evan S. Dellon, MD, MPH, AGAF, professor of gastroenterology and hepatology and director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina School of Medicine, Chapel Hill, North Carolina.

“EoE is becoming more common,” Dellon said. “Healthcare providers should expect to see EoE in their practices, including in the primary care setting, emergency departments, allergy practices, GI [gastrointestinal] practices, ENT clinics, and endoscopy suites.”

The study was published in Clinical Gastroenterology and Hepatology.

Estimating EoE Prevalence

Dellon and colleagues analyzed the Merative MarketScan Commercial Claims and Encounters and Medicare Fee-for-Service databases to calculate the annual prevalence of EoE, as well as age- and sex-stratified estimates standardized to the US population. They also calculated healthcare utilization, including medications and endoscopic procedures, to estimate annual EoE-associated costs. Since the EoE billing code was introduced in 2008, the analysis included 2009-2022 MarketScan and 2009-2017 Medicare data.

In the MarketScan database, the research team identified 20,435 EoE cases in 2022, with a mean age of 38 years, 16% younger than 18 years, 62% men, and 41% with a comorbid allergic disease code. The most common symptoms and diagnoses were dysphagia (39%), abdominal pain or dyspepsia (24%), and esophageal stricture (19%). Over time, patients also had previous codes for comorbid allergic diseases (64%), dysphagia (62%), or esophageal stricture (32%).

In the Medicare database, the research team identified 1913 EoE cases in 2017, with a mean age of 73 years, 47% men, 90% non-Hispanic White, and 36% with a comorbid allergic disease. The most common symptoms and diagnoses were dysphagia (49%), abdominal pain or dyspepsia (35%), and esophageal stricture (30%). Over time, patients also had codes for comorbid allergic diseases (64%), dysphagia (65%), or esophageal stricture (42%).

The database numbers translated to EoE prevalences of about 163 cases per 100,000 people in MarketScan in 2022 and 64 cases per 100,000 people in Medicare in 2017. Since 2009, there has been a fivefold increase in prevalence in both databases.

In MarketScan, the prevalence was higher among men than among women, at 204 vs 122 cases per 100,000 people. For both sexes, peak prevalence occurred between ages 40 and 44.

In Medicare, prevalence was also higher among men than among women, at 79 vs 55 cases per 100,000 people. Peak prevalence occurred between ages 65 and 69.

Standardized to the US population, EoE prevalence was 142.5 cases per 100,000 people, extrapolating to 472,380 cases. The overall prevalence was approximately 1 in 700, with rates of 1 in 617 for those younger than 65 years and 1 in 1562 for those aged ≥ 65 years.

“The rapidly increasing prevalence year over year for the entire timeframe of the study was surprising, as were our estimates of the total number of EoE patients in the US, which suggests that EoE is no longer a rare disease and is now seen in about 1 in 700 people,” Dellon said. “This almost triples our prior estimates of 1 in 2000 from 10 years ago, with all trends suggesting that the prevalence will continue to increase.”

 

Calculating EoE Costs

In terms of procedures, endoscopy with dilation or biopsy was used in about 60%-70% of patients with EoE in both MarketScan and Medicare during the years analyzed. In addition, upper endoscopy with biopsy was coded in 80%-90% of patients, guidewire-based dilation in 11%-17% of patients, and balloon-based dilation in 13%-20% of patients.

In terms of prescription medications, proton pump inhibitors (41%) and topical steroids (26%) were the most common in MarketScan in 2022, as well as in Medicare in 2017, at 32% and 9%, respectively.

When looking at costs by age and sex, the male cohort with the highest costs was aged 10-14 years, estimated at $106.7 million. Among the female cohort, the highest costs were associated with ages 15-19, estimated at $46.5 million.

Overall, total EoE-associated healthcare costs were estimated to be $1.04 billion in 2017, and when adjusted for inflation, the costs were estimated at $1.32 billion in 2024. This is likely an underestimate, the authors wrote, given that EoE prevalence has likely increased for ages 65 or older since 2017 and for all ages since 2022.

“Researching the prevalence and costs is essential to improving patient care by highlighting the growing burden of this recently recognized and growing chronic disease, guiding policy and insurer decisions, and advocating for better access to effective treatments and support for patients,” said Joy Chang, MD, assistant professor of medicine in the Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan.Chang, who wasn’t involved with this study, specializes in eosinophilic GI diseases and researches patient-physician preferences and decision-making in EoE care.

“Clinicians should remain vigilant for symptoms, utilize guideline-based diagnostic approaches, and consider both medical and dietary treatment strategies to optimize patient outcomes and reduce long-term costs,” she said. “Increased awareness and timely intervention can help mitigate the growing impact of this chronic condition.”

The study was supported by a National Institutes of Health grant and used resources from the University of North Carolina Center for Gastrointestinal Biology and Disease. Dellon reported receiving research funding from and having consultant roles with numerous pharmaceutical companies and organizations. Chang reported having no relevant disclosures.

A version of this article appeared on Medscape.com.

The numbers don’t lie: Colorectal cancer (CRC) has been on the rise in younger people in the United States for over two decades.

While the data show a clear trend, researchers still face a glaring unanswered question: Why is this happening?

A recent report in Nature may offer an important clue to start unraveling this early-onset CRC mystery.

 

What the Study Found

The new analysis found that childhood exposure to a carcinogenic toxin known to cause DNA damage is strongly linked to the development of early-onset CRC.

The bacterial toxin, called colibactin, is produced by certain strains of Escherichia coli and other bacteria — more specifically, polyketide synthase (PKS)–positive strains. Previous research has found colibactin-related mutations can occur in up to 15% of CRC cases overall, but a link to early-onset disease has been less clear.

In this recent genetic analysis, investigators led by Marcos Díaz-Gay, PhD, analyzed CRC biopsies from 981 patients across 11 countries and 4 continents. The team tracked DNA damage from colibactin by identifying distinctive mutational signatures — called SBS88 and ID18 — left by the toxin.

Díaz-Gay and colleagues found that these mutational signatures were 3.3 times more common in patients diagnosed before 40 years of age than in those over 70 years.

Colibactin exposure was also linked to about a quarter of mutations that inactivate the colorectal tumor suppressor gene APC.

However, epidemiologic factors linked to CRC, such as body mass index, diet, and lifestyle, were not considered in the study, which the investigators noted is a key limitation.

“Our results show for the first time an association between the presence of colibactin-induced mutational signatures and early-onset colorectal cancer,” Díaz-Gay, a genomic researcher at the Spanish National Cancer Research Center, Madrid, Spain, and colleagues wrote.

“Prior studies have indicated that mutagenesis due to colibactin exposure can occur within the first decade of life and then ceases,” the investigators explained. But “this ‘head start’ could plausibly result in an increased risk of early-onset cancers.”

 

What the Study Means

Trevor Graham, PhD, a professor of genomics and evolution at The Institute of Cancer Research, London, England, helped put the study findings into context.

Others have proposed that colibactin “could have a role in causing early-onset disease,” Graham commented in a statement from the UK nonprofit Science Media Centre. “This work provides [the] strong[est] data yet that the hypothesis is correct.”

Plus, Graham added, “This is very good quality research. The authors have collected bowel cancers from countries around the world and performed whole genome sequencing on them.”

“Most importantly,” he said, the colibactin mutations were more common in people who got bowel cancer before 50 years of age, which “suggests the mutations caused by these bugs in the bowel could be a cause of early-onset bowel cancer, although further studies are needed to confirm this.”

Although the study doesn’t prove causation, “this is a very important finding,” Alan Venook, MD, a gastrointestinal medical oncologist and CRC specialist at the University of California, San Francisco, told GI & Hepatology News. “This gives us a hook to understand what’s going on.”

However, “it’s not at all likely that this single entity is entirely responsible for early-onset CRC,” Venook clarified.

But if childhood exposure to colibactin is responsible, at least in part, for the growing incidence of early-onset CRC, it would suggest that PKS-positive bacteria have become more common in the gut microbiome of younger people over the past few decades. PKS-positive E coli are common, in general — found in up to 20% of healthy people and about 67% of patients with CRC.

If these bacteria are becoming more common in younger people, the reason isn’t yet clear. “The working hypothesis is overuse of antibiotics in young kids,” said Venook, who is collaborating with colleagues to launch an additional multi-institution investigation into the issue.

There are also clinical implications if the findings pan out, Venook said.

This work could lead to a diagnostic test — perhaps one looking for circulating mutational DNA in the blood — that could “give us a leg up on who’s at risk for early-onset CRC,” Venook said. “That’s how this could really make a difference.”

The work was funded by the National Institutes of Health, Cancer Research UK, and others. Several investigators disclosed ties to io9, Inocras, Hologic, Quotient Therapeutics, and Microbiotica. Venook didn’t have any disclosures; disclosure information for Graham was unavailable.

A version of this article appeared on Medscape.com.

The numbers don’t lie: Colorectal cancer (CRC) has been on the rise in younger people in the United States for over two decades.

While the data show a clear trend, researchers still face a glaring unanswered question: Why is this happening?

A recent report in Nature may offer an important clue to start unraveling this early-onset CRC mystery.

 

What the Study Found

The new analysis found that childhood exposure to a carcinogenic toxin known to cause DNA damage is strongly linked to the development of early-onset CRC.

The bacterial toxin, called colibactin, is produced by certain strains of Escherichia coli and other bacteria — more specifically, polyketide synthase (PKS)–positive strains. Previous research has found colibactin-related mutations can occur in up to 15% of CRC cases overall, but a link to early-onset disease has been less clear.

In this recent genetic analysis, investigators led by Marcos Díaz-Gay, PhD, analyzed CRC biopsies from 981 patients across 11 countries and 4 continents. The team tracked DNA damage from colibactin by identifying distinctive mutational signatures — called SBS88 and ID18 — left by the toxin.

Díaz-Gay and colleagues found that these mutational signatures were 3.3 times more common in patients diagnosed before 40 years of age than in those over 70 years.

Colibactin exposure was also linked to about a quarter of mutations that inactivate the colorectal tumor suppressor gene APC.

However, epidemiologic factors linked to CRC, such as body mass index, diet, and lifestyle, were not considered in the study, which the investigators noted is a key limitation.

“Our results show for the first time an association between the presence of colibactin-induced mutational signatures and early-onset colorectal cancer,” Díaz-Gay, a genomic researcher at the Spanish National Cancer Research Center, Madrid, Spain, and colleagues wrote.

“Prior studies have indicated that mutagenesis due to colibactin exposure can occur within the first decade of life and then ceases,” the investigators explained. But “this ‘head start’ could plausibly result in an increased risk of early-onset cancers.”

 

What the Study Means

Trevor Graham, PhD, a professor of genomics and evolution at The Institute of Cancer Research, London, England, helped put the study findings into context.

Others have proposed that colibactin “could have a role in causing early-onset disease,” Graham commented in a statement from the UK nonprofit Science Media Centre. “This work provides [the] strong[est] data yet that the hypothesis is correct.”

Plus, Graham added, “This is very good quality research. The authors have collected bowel cancers from countries around the world and performed whole genome sequencing on them.”

“Most importantly,” he said, the colibactin mutations were more common in people who got bowel cancer before 50 years of age, which “suggests the mutations caused by these bugs in the bowel could be a cause of early-onset bowel cancer, although further studies are needed to confirm this.”

Although the study doesn’t prove causation, “this is a very important finding,” Alan Venook, MD, a gastrointestinal medical oncologist and CRC specialist at the University of California, San Francisco, told GI & Hepatology News. “This gives us a hook to understand what’s going on.”

However, “it’s not at all likely that this single entity is entirely responsible for early-onset CRC,” Venook clarified.

But if childhood exposure to colibactin is responsible, at least in part, for the growing incidence of early-onset CRC, it would suggest that PKS-positive bacteria have become more common in the gut microbiome of younger people over the past few decades. PKS-positive E coli are common, in general — found in up to 20% of healthy people and about 67% of patients with CRC.

If these bacteria are becoming more common in younger people, the reason isn’t yet clear. “The working hypothesis is overuse of antibiotics in young kids,” said Venook, who is collaborating with colleagues to launch an additional multi-institution investigation into the issue.

There are also clinical implications if the findings pan out, Venook said.

This work could lead to a diagnostic test — perhaps one looking for circulating mutational DNA in the blood — that could “give us a leg up on who’s at risk for early-onset CRC,” Venook said. “That’s how this could really make a difference.”

The work was funded by the National Institutes of Health, Cancer Research UK, and others. Several investigators disclosed ties to io9, Inocras, Hologic, Quotient Therapeutics, and Microbiotica. Venook didn’t have any disclosures; disclosure information for Graham was unavailable.

A version of this article appeared on Medscape.com.

The numbers don’t lie: Colorectal cancer (CRC) has been on the rise in younger people in the United States for over two decades.

While the data show a clear trend, researchers still face a glaring unanswered question: Why is this happening?

A recent report in Nature may offer an important clue to start unraveling this early-onset CRC mystery.

 

What the Study Found

The new analysis found that childhood exposure to a carcinogenic toxin known to cause DNA damage is strongly linked to the development of early-onset CRC.

The bacterial toxin, called colibactin, is produced by certain strains of Escherichia coli and other bacteria — more specifically, polyketide synthase (PKS)–positive strains. Previous research has found colibactin-related mutations can occur in up to 15% of CRC cases overall, but a link to early-onset disease has been less clear.

In this recent genetic analysis, investigators led by Marcos Díaz-Gay, PhD, analyzed CRC biopsies from 981 patients across 11 countries and 4 continents. The team tracked DNA damage from colibactin by identifying distinctive mutational signatures — called SBS88 and ID18 — left by the toxin.

Díaz-Gay and colleagues found that these mutational signatures were 3.3 times more common in patients diagnosed before 40 years of age than in those over 70 years.

Colibactin exposure was also linked to about a quarter of mutations that inactivate the colorectal tumor suppressor gene APC.

However, epidemiologic factors linked to CRC, such as body mass index, diet, and lifestyle, were not considered in the study, which the investigators noted is a key limitation.

“Our results show for the first time an association between the presence of colibactin-induced mutational signatures and early-onset colorectal cancer,” Díaz-Gay, a genomic researcher at the Spanish National Cancer Research Center, Madrid, Spain, and colleagues wrote.

“Prior studies have indicated that mutagenesis due to colibactin exposure can occur within the first decade of life and then ceases,” the investigators explained. But “this ‘head start’ could plausibly result in an increased risk of early-onset cancers.”

 

What the Study Means

Trevor Graham, PhD, a professor of genomics and evolution at The Institute of Cancer Research, London, England, helped put the study findings into context.

Others have proposed that colibactin “could have a role in causing early-onset disease,” Graham commented in a statement from the UK nonprofit Science Media Centre. “This work provides [the] strong[est] data yet that the hypothesis is correct.”

Plus, Graham added, “This is very good quality research. The authors have collected bowel cancers from countries around the world and performed whole genome sequencing on them.”

“Most importantly,” he said, the colibactin mutations were more common in people who got bowel cancer before 50 years of age, which “suggests the mutations caused by these bugs in the bowel could be a cause of early-onset bowel cancer, although further studies are needed to confirm this.”

Although the study doesn’t prove causation, “this is a very important finding,” Alan Venook, MD, a gastrointestinal medical oncologist and CRC specialist at the University of California, San Francisco, told GI & Hepatology News. “This gives us a hook to understand what’s going on.”

However, “it’s not at all likely that this single entity is entirely responsible for early-onset CRC,” Venook clarified.

But if childhood exposure to colibactin is responsible, at least in part, for the growing incidence of early-onset CRC, it would suggest that PKS-positive bacteria have become more common in the gut microbiome of younger people over the past few decades. PKS-positive E coli are common, in general — found in up to 20% of healthy people and about 67% of patients with CRC.

If these bacteria are becoming more common in younger people, the reason isn’t yet clear. “The working hypothesis is overuse of antibiotics in young kids,” said Venook, who is collaborating with colleagues to launch an additional multi-institution investigation into the issue.

There are also clinical implications if the findings pan out, Venook said.

This work could lead to a diagnostic test — perhaps one looking for circulating mutational DNA in the blood — that could “give us a leg up on who’s at risk for early-onset CRC,” Venook said. “That’s how this could really make a difference.”

The work was funded by the National Institutes of Health, Cancer Research UK, and others. Several investigators disclosed ties to io9, Inocras, Hologic, Quotient Therapeutics, and Microbiotica. Venook didn’t have any disclosures; disclosure information for Graham was unavailable.

A version of this article appeared on Medscape.com.

Adult patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate or advanced liver fibrosis showed improved liver histology with a once-weekly dose of semaglutide (Wegovy), an ongoing randomized placebo-controlled trial reported.

The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.

Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.

 

A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.

“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.” 

 

Study Details

From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.

All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.

Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).

In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.

Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).

A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001). 

In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001). 

The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms. 

The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit. 

Gastrointestinal adverse events were more common in the semaglutide group.

 

Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”

Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.” 

“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.” 

He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”

According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”

This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.

A version of this article appeared on Medscape.com.

Adult patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate or advanced liver fibrosis showed improved liver histology with a once-weekly dose of semaglutide (Wegovy), an ongoing randomized placebo-controlled trial reported.

The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.

Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.

 

A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.

“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.” 

 

Study Details

From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.

All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.

Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).

In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.

Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).

A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001). 

In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001). 

The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms. 

The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit. 

Gastrointestinal adverse events were more common in the semaglutide group.

 

Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”

Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.” 

“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.” 

He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”

According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”

This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.

A version of this article appeared on Medscape.com.

Adult patients with metabolic dysfunction–associated steatohepatitis (MASH) and moderate or advanced liver fibrosis showed improved liver histology with a once-weekly dose of semaglutide (Wegovy), an ongoing randomized placebo-controlled trial reported.

The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.

Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.

 

A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.

“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.” 

 

Study Details

From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.

All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.

Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).

In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.

Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).

A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001). 

In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001). 

The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms. 

The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit. 

Gastrointestinal adverse events were more common in the semaglutide group.

 

Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”

Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.” 

“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.” 

He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”

According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”

This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.

A version of this article appeared on Medscape.com.

An experimental study in zebrafish has suggested the decades-old, first-generation antihistamine chlorcyclizine and/or other antihistamines may be a strategy for treating erythropoietic protoporphyria (EPP)-associated liver disease by decreasing hepatic protoporphorin IX (PP-IX) accumulation.

Currently, liver transplantation is the primary treatment for this rare, painful, and life-threatening genetic disease, which is caused by excessive PP-IX accumulation and affects about 4000 people in the United States.

The findings could eventually lead to a simpler treatment that prevent shepatic damage at a much earlier stage, according to researchers led by M. Bishr Omary, MD, PhD, a professor in the Center for Advanced Biotechnology and Medicine and Robert Wood Johnson Medical School at Rutgers University in Piscataway, New Jersey.

Reporting in Cellular and Molecular Gastroenterology and Hepatology, the investigators found that chlorcyclizine reduced PP-IX levels. EPP is caused by mutations leading to deficiency of the enzyme ferrochelatase, which inserts iron into PP-IX to generate heme. The resulting condition is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. “Despite available drugs that address photosensitivity, the treatment of EPP-related liver disease remains an unmet need,” Omary and colleagues wrote.

 

The Study

In order to trigger PP-IX overproduction and accumulation, the investigators administered delta-aminolevulinic acid and deferoxamine to zebrafish. These freshwater tropical fish share many physiological characteristics with humans and have been used to model human disease and develop drugs. Furthermore, these fish are transparent at the larval stage, allowing quantification and visualization of porphyrin, which is fluorescent.

The researchers had screened some 2500 approved and bioactive compounds and identified chlorcyclizine as a potent PP-IX–lowering agent.

High-throughput compound screening of ALA + DFO-treated zebrafish found that the HH-1 blocker reduced zebrafish liver PP-IX levels. The effect of chlorcyclizine was validated in porphyrin-loaded primary mouse hepatocytes, transgenic mice, and mice fed the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine. 

Plasma and tissue PP-IX were measured by fluorescence; livers were analyzed by histology, immunoblotting, and quantitative polymerase chain reaction.

Chlorcyclizine-treated zebrafish larvae as well as the two types of mice all showed reduced hepatic PP-IX levels compared with controls. While the neurotransmitter played an important role in PP-IX accumulation in porphyrin-stressed hepatocytes, blockading notably decreased PP-IX levels. 

Detailed analysis showed that chlorcyclizine appeared to work through multiple mechanisms, helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of histamine-producing mast cells. The result was less liver injury, decreased porphyrin-triggered protein aggregation and oxidation, and increased clearance of s PP-I in stool.

Interestingly, in both mouse models, chlorcyclizine lowered PP-IX levels in female but not male mice in liver, erythrocytes, and bone marrow. This sex-specific effect appeared to be related to the greater speed at which male murines metabolize the drug, the authors explained in a news release. In rats, for example, the metabolism of chlorcyclizine is 8 times higher in male than in female livers. 

The investigators plan to launch a clinical trial in EPP patients to evaluate the effectiveness of chlorcyclizine for both liver and skin involvement. And a phase 2 trial is already underway testing the antacid cimetidine for treating EPP skin manifestations. It is possible that the different antihistamines may act additively or synergistically.

This work was supported by National Institutes of Health (NIH) grants and the Henry and Mala Dorfman Family Professorship of Pediatric Hematology/Oncology.

Omary is a member of the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Data and Safety Monitoring Board of the Porphyrias Consortium.

A provisional patent application has been submitted for the use of H1-receptor blockers with or without receptor blockers to treat protoporphyrias associated with PP-IX accumulation.
 

An experimental study in zebrafish has suggested the decades-old, first-generation antihistamine chlorcyclizine and/or other antihistamines may be a strategy for treating erythropoietic protoporphyria (EPP)-associated liver disease by decreasing hepatic protoporphorin IX (PP-IX) accumulation.

Currently, liver transplantation is the primary treatment for this rare, painful, and life-threatening genetic disease, which is caused by excessive PP-IX accumulation and affects about 4000 people in the United States.

The findings could eventually lead to a simpler treatment that prevent shepatic damage at a much earlier stage, according to researchers led by M. Bishr Omary, MD, PhD, a professor in the Center for Advanced Biotechnology and Medicine and Robert Wood Johnson Medical School at Rutgers University in Piscataway, New Jersey.

Reporting in Cellular and Molecular Gastroenterology and Hepatology, the investigators found that chlorcyclizine reduced PP-IX levels. EPP is caused by mutations leading to deficiency of the enzyme ferrochelatase, which inserts iron into PP-IX to generate heme. The resulting condition is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. “Despite available drugs that address photosensitivity, the treatment of EPP-related liver disease remains an unmet need,” Omary and colleagues wrote.

 

The Study

In order to trigger PP-IX overproduction and accumulation, the investigators administered delta-aminolevulinic acid and deferoxamine to zebrafish. These freshwater tropical fish share many physiological characteristics with humans and have been used to model human disease and develop drugs. Furthermore, these fish are transparent at the larval stage, allowing quantification and visualization of porphyrin, which is fluorescent.

The researchers had screened some 2500 approved and bioactive compounds and identified chlorcyclizine as a potent PP-IX–lowering agent.

High-throughput compound screening of ALA + DFO-treated zebrafish found that the HH-1 blocker reduced zebrafish liver PP-IX levels. The effect of chlorcyclizine was validated in porphyrin-loaded primary mouse hepatocytes, transgenic mice, and mice fed the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine. 

Plasma and tissue PP-IX were measured by fluorescence; livers were analyzed by histology, immunoblotting, and quantitative polymerase chain reaction.

Chlorcyclizine-treated zebrafish larvae as well as the two types of mice all showed reduced hepatic PP-IX levels compared with controls. While the neurotransmitter played an important role in PP-IX accumulation in porphyrin-stressed hepatocytes, blockading notably decreased PP-IX levels. 

Detailed analysis showed that chlorcyclizine appeared to work through multiple mechanisms, helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of histamine-producing mast cells. The result was less liver injury, decreased porphyrin-triggered protein aggregation and oxidation, and increased clearance of s PP-I in stool.

Interestingly, in both mouse models, chlorcyclizine lowered PP-IX levels in female but not male mice in liver, erythrocytes, and bone marrow. This sex-specific effect appeared to be related to the greater speed at which male murines metabolize the drug, the authors explained in a news release. In rats, for example, the metabolism of chlorcyclizine is 8 times higher in male than in female livers. 

The investigators plan to launch a clinical trial in EPP patients to evaluate the effectiveness of chlorcyclizine for both liver and skin involvement. And a phase 2 trial is already underway testing the antacid cimetidine for treating EPP skin manifestations. It is possible that the different antihistamines may act additively or synergistically.

This work was supported by National Institutes of Health (NIH) grants and the Henry and Mala Dorfman Family Professorship of Pediatric Hematology/Oncology.

Omary is a member of the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Data and Safety Monitoring Board of the Porphyrias Consortium.

A provisional patent application has been submitted for the use of H1-receptor blockers with or without receptor blockers to treat protoporphyrias associated with PP-IX accumulation.
 

An experimental study in zebrafish has suggested the decades-old, first-generation antihistamine chlorcyclizine and/or other antihistamines may be a strategy for treating erythropoietic protoporphyria (EPP)-associated liver disease by decreasing hepatic protoporphorin IX (PP-IX) accumulation.

Currently, liver transplantation is the primary treatment for this rare, painful, and life-threatening genetic disease, which is caused by excessive PP-IX accumulation and affects about 4000 people in the United States.

The findings could eventually lead to a simpler treatment that prevent shepatic damage at a much earlier stage, according to researchers led by M. Bishr Omary, MD, PhD, a professor in the Center for Advanced Biotechnology and Medicine and Robert Wood Johnson Medical School at Rutgers University in Piscataway, New Jersey.

Reporting in Cellular and Molecular Gastroenterology and Hepatology, the investigators found that chlorcyclizine reduced PP-IX levels. EPP is caused by mutations leading to deficiency of the enzyme ferrochelatase, which inserts iron into PP-IX to generate heme. The resulting condition is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. “Despite available drugs that address photosensitivity, the treatment of EPP-related liver disease remains an unmet need,” Omary and colleagues wrote.

 

The Study

In order to trigger PP-IX overproduction and accumulation, the investigators administered delta-aminolevulinic acid and deferoxamine to zebrafish. These freshwater tropical fish share many physiological characteristics with humans and have been used to model human disease and develop drugs. Furthermore, these fish are transparent at the larval stage, allowing quantification and visualization of porphyrin, which is fluorescent.

The researchers had screened some 2500 approved and bioactive compounds and identified chlorcyclizine as a potent PP-IX–lowering agent.

High-throughput compound screening of ALA + DFO-treated zebrafish found that the HH-1 blocker reduced zebrafish liver PP-IX levels. The effect of chlorcyclizine was validated in porphyrin-loaded primary mouse hepatocytes, transgenic mice, and mice fed the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine. 

Plasma and tissue PP-IX were measured by fluorescence; livers were analyzed by histology, immunoblotting, and quantitative polymerase chain reaction.

Chlorcyclizine-treated zebrafish larvae as well as the two types of mice all showed reduced hepatic PP-IX levels compared with controls. While the neurotransmitter played an important role in PP-IX accumulation in porphyrin-stressed hepatocytes, blockading notably decreased PP-IX levels. 

Detailed analysis showed that chlorcyclizine appeared to work through multiple mechanisms, helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of histamine-producing mast cells. The result was less liver injury, decreased porphyrin-triggered protein aggregation and oxidation, and increased clearance of s PP-I in stool.

Interestingly, in both mouse models, chlorcyclizine lowered PP-IX levels in female but not male mice in liver, erythrocytes, and bone marrow. This sex-specific effect appeared to be related to the greater speed at which male murines metabolize the drug, the authors explained in a news release. In rats, for example, the metabolism of chlorcyclizine is 8 times higher in male than in female livers. 

The investigators plan to launch a clinical trial in EPP patients to evaluate the effectiveness of chlorcyclizine for both liver and skin involvement. And a phase 2 trial is already underway testing the antacid cimetidine for treating EPP skin manifestations. It is possible that the different antihistamines may act additively or synergistically.

This work was supported by National Institutes of Health (NIH) grants and the Henry and Mala Dorfman Family Professorship of Pediatric Hematology/Oncology.

Omary is a member of the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Data and Safety Monitoring Board of the Porphyrias Consortium.

A provisional patent application has been submitted for the use of H1-receptor blockers with or without receptor blockers to treat protoporphyrias associated with PP-IX accumulation.
 

An irritable bowel syndrome (IBS) elimination diet based on a novel IBS–specific, immunoglobulin G (IgG) was superior to a sham diet for abdominal pain, an 8-center, randomized double-blind controlled trial found.

While elimination diets can provide a personalized approach to dietary therapy, existing studies have had serious methodological issues, noted lead author Prashant Singh, MBBS, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Mich., and colleagues in Gastroenterology.

For example, previous studies on IgG-based diets used assays developed without determining IBS trigger foods or establishing a 95% confidence interval–based cutoff using a healthy control comparison group.

 

Study Details

From June 2018 to December 2021, 238 IBS patients testing positive for at least one food on 18-food IgG ELISA (enzyme-linked immunosorbent assay) testing and an average daily abdominal pain intensity score of 3.0 to 7.5 on an 11.0-point scale during a 2-week run-in period were randomized for 8 weeks to an experimental antibody-guided diet or to a sham diet. The primary outcome was a 30% decrease in abdominal pain intensity (API) for 2 of the last 4 weeks of treatment.

The overall study population had a mean age of about 40 years, and more than three-quarters were female. The 3 IBS types – constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed bowel habits-predominant (IBS-M) – accounted for about a third each in both arms.

The experimental diet eliminated foods based on a positive ELISA result. Its sham counterpart had the same number of foods removed as the number of positive-testing food sensitivities, but the foods eliminated in the sham diet had tested negative on the IgG assay.

Participants reported daily abdominal pain intensity, bloating, and stool consistency, and frequency. They also reported dietary compliance and daily medication use.

Of the 238 randomized adults, 223 were included in the modified intention-to-treat analysis. A significantly greater proportion of subjects in the experimental group met the primary outcome than those in the sham group: 59.6% vs 42.1%, P = .02). “This highlights the potential effectiveness of a personalized elimination diet based on a novel IBS-specific IgG assay,” the authors wrote.

Symptom improvement between arms began to separate out at around 2 weeks, suggesting the effect of the experimental diet was relatively rapid in onset, and continued for at least 8 weeks. The durability of response, however, needs to be assessed in future studies “and it is unclear if there is a role for repeat IgG testing to monitor treatment response,” the authors wrote.

Subgroup analysis revealed that a higher proportion of those with IBS-C and IBS-M in the experimental diet group met the primary endpoint vs the sham group: 67.1% vs 35.8% and 66% vs 29.5%, respectively.

Interestingly, more patients in the experimental arm were noncompliant with their diet. “It is possible that subjects found the experimental diet more difficult to comply with compared with the sham diet or that because the experimental diet was more likely to improve symptoms, dietary indiscretion may have been more common in this group (a phenomenon seen with other elimination diets such as gluten-free diet in celiac disease),” the authors wrote.

Adverse events, deemed unrelated to either regimen, were 3 in the experimental arm vs 8 in the sham arm, which had 2 urinary tract infections.

The authors called for a larger, adequately powered study to assess the efficacy of an elimination diet based on this novel immunoglobulin G assay in patients with IBS-C and IBS-M. Future studies should perform detailed adherence assessments using food diaries.

“Mechanisms of how immunoglobulin G-antibody response to food antigen generates symptoms in irritable bowel syndrome are not well understood. Delineating this might provide new insights into food-related irritable bowel syndrome pathophysiology,” they concluded.

This study was funded by Biomerica Inc.

An irritable bowel syndrome (IBS) elimination diet based on a novel IBS–specific, immunoglobulin G (IgG) was superior to a sham diet for abdominal pain, an 8-center, randomized double-blind controlled trial found.

While elimination diets can provide a personalized approach to dietary therapy, existing studies have had serious methodological issues, noted lead author Prashant Singh, MBBS, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Mich., and colleagues in Gastroenterology.

For example, previous studies on IgG-based diets used assays developed without determining IBS trigger foods or establishing a 95% confidence interval–based cutoff using a healthy control comparison group.

 

Study Details

From June 2018 to December 2021, 238 IBS patients testing positive for at least one food on 18-food IgG ELISA (enzyme-linked immunosorbent assay) testing and an average daily abdominal pain intensity score of 3.0 to 7.5 on an 11.0-point scale during a 2-week run-in period were randomized for 8 weeks to an experimental antibody-guided diet or to a sham diet. The primary outcome was a 30% decrease in abdominal pain intensity (API) for 2 of the last 4 weeks of treatment.

The overall study population had a mean age of about 40 years, and more than three-quarters were female. The 3 IBS types – constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed bowel habits-predominant (IBS-M) – accounted for about a third each in both arms.

The experimental diet eliminated foods based on a positive ELISA result. Its sham counterpart had the same number of foods removed as the number of positive-testing food sensitivities, but the foods eliminated in the sham diet had tested negative on the IgG assay.

Participants reported daily abdominal pain intensity, bloating, and stool consistency, and frequency. They also reported dietary compliance and daily medication use.

Of the 238 randomized adults, 223 were included in the modified intention-to-treat analysis. A significantly greater proportion of subjects in the experimental group met the primary outcome than those in the sham group: 59.6% vs 42.1%, P = .02). “This highlights the potential effectiveness of a personalized elimination diet based on a novel IBS-specific IgG assay,” the authors wrote.

Symptom improvement between arms began to separate out at around 2 weeks, suggesting the effect of the experimental diet was relatively rapid in onset, and continued for at least 8 weeks. The durability of response, however, needs to be assessed in future studies “and it is unclear if there is a role for repeat IgG testing to monitor treatment response,” the authors wrote.

Subgroup analysis revealed that a higher proportion of those with IBS-C and IBS-M in the experimental diet group met the primary endpoint vs the sham group: 67.1% vs 35.8% and 66% vs 29.5%, respectively.

Interestingly, more patients in the experimental arm were noncompliant with their diet. “It is possible that subjects found the experimental diet more difficult to comply with compared with the sham diet or that because the experimental diet was more likely to improve symptoms, dietary indiscretion may have been more common in this group (a phenomenon seen with other elimination diets such as gluten-free diet in celiac disease),” the authors wrote.

Adverse events, deemed unrelated to either regimen, were 3 in the experimental arm vs 8 in the sham arm, which had 2 urinary tract infections.

The authors called for a larger, adequately powered study to assess the efficacy of an elimination diet based on this novel immunoglobulin G assay in patients with IBS-C and IBS-M. Future studies should perform detailed adherence assessments using food diaries.

“Mechanisms of how immunoglobulin G-antibody response to food antigen generates symptoms in irritable bowel syndrome are not well understood. Delineating this might provide new insights into food-related irritable bowel syndrome pathophysiology,” they concluded.

This study was funded by Biomerica Inc.

An irritable bowel syndrome (IBS) elimination diet based on a novel IBS–specific, immunoglobulin G (IgG) was superior to a sham diet for abdominal pain, an 8-center, randomized double-blind controlled trial found.

While elimination diets can provide a personalized approach to dietary therapy, existing studies have had serious methodological issues, noted lead author Prashant Singh, MBBS, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Mich., and colleagues in Gastroenterology.

For example, previous studies on IgG-based diets used assays developed without determining IBS trigger foods or establishing a 95% confidence interval–based cutoff using a healthy control comparison group.

 

Study Details

From June 2018 to December 2021, 238 IBS patients testing positive for at least one food on 18-food IgG ELISA (enzyme-linked immunosorbent assay) testing and an average daily abdominal pain intensity score of 3.0 to 7.5 on an 11.0-point scale during a 2-week run-in period were randomized for 8 weeks to an experimental antibody-guided diet or to a sham diet. The primary outcome was a 30% decrease in abdominal pain intensity (API) for 2 of the last 4 weeks of treatment.

The overall study population had a mean age of about 40 years, and more than three-quarters were female. The 3 IBS types – constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed bowel habits-predominant (IBS-M) – accounted for about a third each in both arms.

The experimental diet eliminated foods based on a positive ELISA result. Its sham counterpart had the same number of foods removed as the number of positive-testing food sensitivities, but the foods eliminated in the sham diet had tested negative on the IgG assay.

Participants reported daily abdominal pain intensity, bloating, and stool consistency, and frequency. They also reported dietary compliance and daily medication use.

Of the 238 randomized adults, 223 were included in the modified intention-to-treat analysis. A significantly greater proportion of subjects in the experimental group met the primary outcome than those in the sham group: 59.6% vs 42.1%, P = .02). “This highlights the potential effectiveness of a personalized elimination diet based on a novel IBS-specific IgG assay,” the authors wrote.

Symptom improvement between arms began to separate out at around 2 weeks, suggesting the effect of the experimental diet was relatively rapid in onset, and continued for at least 8 weeks. The durability of response, however, needs to be assessed in future studies “and it is unclear if there is a role for repeat IgG testing to monitor treatment response,” the authors wrote.

Subgroup analysis revealed that a higher proportion of those with IBS-C and IBS-M in the experimental diet group met the primary endpoint vs the sham group: 67.1% vs 35.8% and 66% vs 29.5%, respectively.

Interestingly, more patients in the experimental arm were noncompliant with their diet. “It is possible that subjects found the experimental diet more difficult to comply with compared with the sham diet or that because the experimental diet was more likely to improve symptoms, dietary indiscretion may have been more common in this group (a phenomenon seen with other elimination diets such as gluten-free diet in celiac disease),” the authors wrote.

Adverse events, deemed unrelated to either regimen, were 3 in the experimental arm vs 8 in the sham arm, which had 2 urinary tract infections.

The authors called for a larger, adequately powered study to assess the efficacy of an elimination diet based on this novel immunoglobulin G assay in patients with IBS-C and IBS-M. Future studies should perform detailed adherence assessments using food diaries.

“Mechanisms of how immunoglobulin G-antibody response to food antigen generates symptoms in irritable bowel syndrome are not well understood. Delineating this might provide new insights into food-related irritable bowel syndrome pathophysiology,” they concluded.

This study was funded by Biomerica Inc.

Clinicians can help reduce gastric cancer incidence and mortality in high-risk groups through endoscopic screening and surveillance of precancerous conditions, such as gastric intestinal metaplasia (GIM), according to a new clinical practice update from AGA.

The update supports additional gastric guidance published so far in 2025, including a clinical guideline on the diagnosis and management of gastric premalignant conditions (GPMC) from the American College of Gastroenterology (ACG) and upper GI endoscopy quality indicators from ACG and the American Society for Gastrointestinal Endoscopy (ASGE).

“The synergy of these three publications coming out at the same time helps us to finally establish surveillance of high-risk gastric conditions in practice, as we do in the colon and esophagus,” said Douglas R. Morgan, MD, professor of medicine in gastroenterology and hepatology and director of Global Health programs in gastroenterology at the University of Alabama at Birmingham.

Morgan, who wasn’t involved with the AGA update, served as lead author for the ACG guideline and co-author of the ACG-ASGE quality indicators. He also co-authored the 2024 ACG clinical guideline on treating Helicobacter pylori infection, which has implications for gastric cancer.

“The AGA and ACG updates provide detail, while the QI document is an enforcer with medical, legal, and reimbursement implications,” he said. “We have an alignment of the stars with this overdue move toward concrete surveillance for high-risk lesions in the stomach.”

The clinical practice update was published in Gastroenterology.

 

Gastric Cancer Screening

Gastric cancer remains a leading cause of preventable cancer and mortality in certain US populations, the authors wrote. The top ways to reduce mortality include primary prevention, particularly by eradicating H pylori, and secondary prevention through screening and surveillance.

High-risk groups in the United States should be considered for gastric cancer screening, including first-generation immigrants from high-incidence regions and potentially other non-White racial and ethnic groups, those with a family history of gastric cancer in a first-degree relative, and those with certain hereditary GI polyposis or hereditary cancer syndromes.

Endoscopy remains the best test for screening or surveillance of high-risk groups, the authors wrote, since it allows for direct visualization to endoscopically stage the mucosa, identify any concerning areas of neoplasia, and enable biopsies. Both endoscopic and histologic staging are key for risk stratification and surveillance decisions.

In particular, clinicians should use a high-definition white light endoscopy system with image enhancement, gastric mucosal cleansing, and insufflation to see the mucosa. As part of this, clinicians should allow for adequate visual inspection time, photodocumentation, and systematic biopsy protocol for mucosal staging, where appropriate.

As part of this, clinicians should consider H pylori eradication as an essential adjunct to endoscopic screening, the authors wrote. Opportunistic screening for H pylori should be considered in high-risk groups, and familial-based testing should be considered among adult household members of patients who test positive for H pylori.

 

Endoscopic Biopsy and Diagnosis

In patients with suspected gastric atrophy — with or without GIM — gastric biopsies should be obtained with a systematic approach, the authors wrote. Clinicians should take a minimum of five biopsies, sampling from the antrum/incisura and corpus.

Endoscopists should work with their pathologists on consistent documentation of histologic risk-stratification parameters when atrophic gastritis is diagnosed, the authors wrote. To inform clinical decision-making, this should include documentation of the presence or absence of H pylori infection, severity of atrophy or metaplasia, and histologic subtyping of GIM.

Although GIM and dysplasia are endoscopically detectable, these findings often go undiagnosed when endoscopists aren’t familiar with the characteristic visual features, the authors wrote. More training is needed, especially in the US, and although artificial intelligence tools appear promising for detecting early gastric neoplasia, data remain too preliminary to recommend routine use, the authors added.

Since indefinite and low-grade dysplasia can be difficult to identify by endoscopy and accurately diagnosis on histopathology, all dysplasia should be confirmed by an experienced gastrointestinal pathologist, the authors wrote. Clinicians should refer patients with visible or nonvisible dysplasia to an endoscopist or center with expertise in gastric neoplasia.

 

Endoscopic Management and Surveillance

If an index screening endoscopy doesn’t identify atrophy, GIM, or neoplasia, ongoing screening should be based on a patient’s risk factors and preferences. If the patient has a family history or multiple risk factors, ongoing screening should be considered. However, the optimal screening intervals in these scenarios aren’t well-defined.

Patients with confirmed gastric atrophy should undergo risk stratification, the authors wrote. Those with severe atrophic gastritis or multifocal/incomplete GIM would likely benefit from endoscopic surveillance, particularly if they have other risk factors such as family history. Surveillance should be considered every 3 years, though shorter intervals may be advisable for those with multiple risk factors such as severe GIM.

Patients with high-grade dysplasia or early gastric cancer should undergo endoscopic submucosal dissection (ESD), with the goal of en bloc, R0 resection to enable accurate pathologic staging and the intent to cure. Eradicating active H pylori infection is essential — but shouldn’t delay endoscopic intervention, the authors wrote.

In addition, patients with a history of successfully resected gastric dysplasia or cancer should undergo endoscopic surveillance. Although post-ESD surveillance intervals have been suggested in other recent AGA clinical practice updates, additional data are needed, particularly for US recommendations, the authors wrote.

Although type 1 gastric carcinoids in patients with atrophic gastritis are typically indolent, especially if less than 1 cm, endoscopists may consider resecting them and should resect lesions between 1and 2 cm. Patients with lesions over 2 cm should undergo cross-sectional imaging and be referred for surgical resection, given the risk for metastasis.

 

Patient-Centered Approach

The guideline authors suggested thinking about screening and surveillance on a patient-level basis. For instance, only those who are fit for endoscopic or potentially surgical treatment should be screened for gastric cancer and continued surveillance of GPMC, they wrote. If a person is no longer fit for endoscopic or surgical treatment, whether due to life expectancy or other comorbidities, then screening should be stopped.

In addition, to achieve health equity, clinicians should take a personalized approach to assess a patient’s risk for gastric cancer and determine whether to pursue screening and surveillance, the authors wrote. Modifiable risk factors — such as tobacco use, high-salt and processed food diets, and lack of health care — should also be addressed, since most of these risk factors disproportionately affect high-risk patients and represent healthcare disparities, they added.

“This update provides clinicians with a framework for understanding the natural history and epidemiology of gastric polyps, as well as guidance on best practices for the endoscopic detection and classification of gastric polyps, best practices for the endoscopic resection of gastric polyps, and best practices for endoscopic surveillance following resection,” said Hashem El-Serag, MD, professor and chair of medicine at the Baylor College of Medicine and director of the Texas Medical Center Digestive Diseases Center in Houston.

El-Serag, who wasn’t involved with the clinical practice update, has researched and published on consensus around the diagnosis and management of GIM.

“Stomach polyps are commonly found during routine endoscopic procedures. They are mostly asymptomatic and incidental, and therefore, clinicians may not be prepared ahead of time on how to deal with them,” he said. “The appropriate management requires proper identification and sampling of the polyp features and the uninvolved gastric mucosa, as well as a clear understanding of the risk factors and prognosis. Recent changes in the epidemiology and endoscopic management of gastric polyps makes this update timely and important.”

The update received no particular funding. The authors disclosed receiving grant support, having consultant relationships with, and serving in advisory roles for numerous pharmaceutical, biomedical, and biotechnology firms. Morgan and El-Serag reported having no relevant disclosures.

A version of this article appeared on Medscape.com.

Clinicians can help reduce gastric cancer incidence and mortality in high-risk groups through endoscopic screening and surveillance of precancerous conditions, such as gastric intestinal metaplasia (GIM), according to a new clinical practice update from AGA.

The update supports additional gastric guidance published so far in 2025, including a clinical guideline on the diagnosis and management of gastric premalignant conditions (GPMC) from the American College of Gastroenterology (ACG) and upper GI endoscopy quality indicators from ACG and the American Society for Gastrointestinal Endoscopy (ASGE).

“The synergy of these three publications coming out at the same time helps us to finally establish surveillance of high-risk gastric conditions in practice, as we do in the colon and esophagus,” said Douglas R. Morgan, MD, professor of medicine in gastroenterology and hepatology and director of Global Health programs in gastroenterology at the University of Alabama at Birmingham.

Morgan, who wasn’t involved with the AGA update, served as lead author for the ACG guideline and co-author of the ACG-ASGE quality indicators. He also co-authored the 2024 ACG clinical guideline on treating Helicobacter pylori infection, which has implications for gastric cancer.

“The AGA and ACG updates provide detail, while the QI document is an enforcer with medical, legal, and reimbursement implications,” he said. “We have an alignment of the stars with this overdue move toward concrete surveillance for high-risk lesions in the stomach.”

The clinical practice update was published in Gastroenterology.

 

Gastric Cancer Screening

Gastric cancer remains a leading cause of preventable cancer and mortality in certain US populations, the authors wrote. The top ways to reduce mortality include primary prevention, particularly by eradicating H pylori, and secondary prevention through screening and surveillance.

High-risk groups in the United States should be considered for gastric cancer screening, including first-generation immigrants from high-incidence regions and potentially other non-White racial and ethnic groups, those with a family history of gastric cancer in a first-degree relative, and those with certain hereditary GI polyposis or hereditary cancer syndromes.

Endoscopy remains the best test for screening or surveillance of high-risk groups, the authors wrote, since it allows for direct visualization to endoscopically stage the mucosa, identify any concerning areas of neoplasia, and enable biopsies. Both endoscopic and histologic staging are key for risk stratification and surveillance decisions.

In particular, clinicians should use a high-definition white light endoscopy system with image enhancement, gastric mucosal cleansing, and insufflation to see the mucosa. As part of this, clinicians should allow for adequate visual inspection time, photodocumentation, and systematic biopsy protocol for mucosal staging, where appropriate.

As part of this, clinicians should consider H pylori eradication as an essential adjunct to endoscopic screening, the authors wrote. Opportunistic screening for H pylori should be considered in high-risk groups, and familial-based testing should be considered among adult household members of patients who test positive for H pylori.

 

Endoscopic Biopsy and Diagnosis

In patients with suspected gastric atrophy — with or without GIM — gastric biopsies should be obtained with a systematic approach, the authors wrote. Clinicians should take a minimum of five biopsies, sampling from the antrum/incisura and corpus.

Endoscopists should work with their pathologists on consistent documentation of histologic risk-stratification parameters when atrophic gastritis is diagnosed, the authors wrote. To inform clinical decision-making, this should include documentation of the presence or absence of H pylori infection, severity of atrophy or metaplasia, and histologic subtyping of GIM.

Although GIM and dysplasia are endoscopically detectable, these findings often go undiagnosed when endoscopists aren’t familiar with the characteristic visual features, the authors wrote. More training is needed, especially in the US, and although artificial intelligence tools appear promising for detecting early gastric neoplasia, data remain too preliminary to recommend routine use, the authors added.

Since indefinite and low-grade dysplasia can be difficult to identify by endoscopy and accurately diagnosis on histopathology, all dysplasia should be confirmed by an experienced gastrointestinal pathologist, the authors wrote. Clinicians should refer patients with visible or nonvisible dysplasia to an endoscopist or center with expertise in gastric neoplasia.

 

Endoscopic Management and Surveillance

If an index screening endoscopy doesn’t identify atrophy, GIM, or neoplasia, ongoing screening should be based on a patient’s risk factors and preferences. If the patient has a family history or multiple risk factors, ongoing screening should be considered. However, the optimal screening intervals in these scenarios aren’t well-defined.

Patients with confirmed gastric atrophy should undergo risk stratification, the authors wrote. Those with severe atrophic gastritis or multifocal/incomplete GIM would likely benefit from endoscopic surveillance, particularly if they have other risk factors such as family history. Surveillance should be considered every 3 years, though shorter intervals may be advisable for those with multiple risk factors such as severe GIM.

Patients with high-grade dysplasia or early gastric cancer should undergo endoscopic submucosal dissection (ESD), with the goal of en bloc, R0 resection to enable accurate pathologic staging and the intent to cure. Eradicating active H pylori infection is essential — but shouldn’t delay endoscopic intervention, the authors wrote.

In addition, patients with a history of successfully resected gastric dysplasia or cancer should undergo endoscopic surveillance. Although post-ESD surveillance intervals have been suggested in other recent AGA clinical practice updates, additional data are needed, particularly for US recommendations, the authors wrote.

Although type 1 gastric carcinoids in patients with atrophic gastritis are typically indolent, especially if less than 1 cm, endoscopists may consider resecting them and should resect lesions between 1and 2 cm. Patients with lesions over 2 cm should undergo cross-sectional imaging and be referred for surgical resection, given the risk for metastasis.

 

Patient-Centered Approach

The guideline authors suggested thinking about screening and surveillance on a patient-level basis. For instance, only those who are fit for endoscopic or potentially surgical treatment should be screened for gastric cancer and continued surveillance of GPMC, they wrote. If a person is no longer fit for endoscopic or surgical treatment, whether due to life expectancy or other comorbidities, then screening should be stopped.

In addition, to achieve health equity, clinicians should take a personalized approach to assess a patient’s risk for gastric cancer and determine whether to pursue screening and surveillance, the authors wrote. Modifiable risk factors — such as tobacco use, high-salt and processed food diets, and lack of health care — should also be addressed, since most of these risk factors disproportionately affect high-risk patients and represent healthcare disparities, they added.

“This update provides clinicians with a framework for understanding the natural history and epidemiology of gastric polyps, as well as guidance on best practices for the endoscopic detection and classification of gastric polyps, best practices for the endoscopic resection of gastric polyps, and best practices for endoscopic surveillance following resection,” said Hashem El-Serag, MD, professor and chair of medicine at the Baylor College of Medicine and director of the Texas Medical Center Digestive Diseases Center in Houston.

El-Serag, who wasn’t involved with the clinical practice update, has researched and published on consensus around the diagnosis and management of GIM.

“Stomach polyps are commonly found during routine endoscopic procedures. They are mostly asymptomatic and incidental, and therefore, clinicians may not be prepared ahead of time on how to deal with them,” he said. “The appropriate management requires proper identification and sampling of the polyp features and the uninvolved gastric mucosa, as well as a clear understanding of the risk factors and prognosis. Recent changes in the epidemiology and endoscopic management of gastric polyps makes this update timely and important.”

The update received no particular funding. The authors disclosed receiving grant support, having consultant relationships with, and serving in advisory roles for numerous pharmaceutical, biomedical, and biotechnology firms. Morgan and El-Serag reported having no relevant disclosures.

A version of this article appeared on Medscape.com.

Clinicians can help reduce gastric cancer incidence and mortality in high-risk groups through endoscopic screening and surveillance of precancerous conditions, such as gastric intestinal metaplasia (GIM), according to a new clinical practice update from AGA.

The update supports additional gastric guidance published so far in 2025, including a clinical guideline on the diagnosis and management of gastric premalignant conditions (GPMC) from the American College of Gastroenterology (ACG) and upper GI endoscopy quality indicators from ACG and the American Society for Gastrointestinal Endoscopy (ASGE).

“The synergy of these three publications coming out at the same time helps us to finally establish surveillance of high-risk gastric conditions in practice, as we do in the colon and esophagus,” said Douglas R. Morgan, MD, professor of medicine in gastroenterology and hepatology and director of Global Health programs in gastroenterology at the University of Alabama at Birmingham.

Morgan, who wasn’t involved with the AGA update, served as lead author for the ACG guideline and co-author of the ACG-ASGE quality indicators. He also co-authored the 2024 ACG clinical guideline on treating Helicobacter pylori infection, which has implications for gastric cancer.

“The AGA and ACG updates provide detail, while the QI document is an enforcer with medical, legal, and reimbursement implications,” he said. “We have an alignment of the stars with this overdue move toward concrete surveillance for high-risk lesions in the stomach.”

The clinical practice update was published in Gastroenterology.

 

Gastric Cancer Screening

Gastric cancer remains a leading cause of preventable cancer and mortality in certain US populations, the authors wrote. The top ways to reduce mortality include primary prevention, particularly by eradicating H pylori, and secondary prevention through screening and surveillance.

High-risk groups in the United States should be considered for gastric cancer screening, including first-generation immigrants from high-incidence regions and potentially other non-White racial and ethnic groups, those with a family history of gastric cancer in a first-degree relative, and those with certain hereditary GI polyposis or hereditary cancer syndromes.

Endoscopy remains the best test for screening or surveillance of high-risk groups, the authors wrote, since it allows for direct visualization to endoscopically stage the mucosa, identify any concerning areas of neoplasia, and enable biopsies. Both endoscopic and histologic staging are key for risk stratification and surveillance decisions.

In particular, clinicians should use a high-definition white light endoscopy system with image enhancement, gastric mucosal cleansing, and insufflation to see the mucosa. As part of this, clinicians should allow for adequate visual inspection time, photodocumentation, and systematic biopsy protocol for mucosal staging, where appropriate.

As part of this, clinicians should consider H pylori eradication as an essential adjunct to endoscopic screening, the authors wrote. Opportunistic screening for H pylori should be considered in high-risk groups, and familial-based testing should be considered among adult household members of patients who test positive for H pylori.

 

Endoscopic Biopsy and Diagnosis

In patients with suspected gastric atrophy — with or without GIM — gastric biopsies should be obtained with a systematic approach, the authors wrote. Clinicians should take a minimum of five biopsies, sampling from the antrum/incisura and corpus.

Endoscopists should work with their pathologists on consistent documentation of histologic risk-stratification parameters when atrophic gastritis is diagnosed, the authors wrote. To inform clinical decision-making, this should include documentation of the presence or absence of H pylori infection, severity of atrophy or metaplasia, and histologic subtyping of GIM.

Although GIM and dysplasia are endoscopically detectable, these findings often go undiagnosed when endoscopists aren’t familiar with the characteristic visual features, the authors wrote. More training is needed, especially in the US, and although artificial intelligence tools appear promising for detecting early gastric neoplasia, data remain too preliminary to recommend routine use, the authors added.

Since indefinite and low-grade dysplasia can be difficult to identify by endoscopy and accurately diagnosis on histopathology, all dysplasia should be confirmed by an experienced gastrointestinal pathologist, the authors wrote. Clinicians should refer patients with visible or nonvisible dysplasia to an endoscopist or center with expertise in gastric neoplasia.

 

Endoscopic Management and Surveillance

If an index screening endoscopy doesn’t identify atrophy, GIM, or neoplasia, ongoing screening should be based on a patient’s risk factors and preferences. If the patient has a family history or multiple risk factors, ongoing screening should be considered. However, the optimal screening intervals in these scenarios aren’t well-defined.

Patients with confirmed gastric atrophy should undergo risk stratification, the authors wrote. Those with severe atrophic gastritis or multifocal/incomplete GIM would likely benefit from endoscopic surveillance, particularly if they have other risk factors such as family history. Surveillance should be considered every 3 years, though shorter intervals may be advisable for those with multiple risk factors such as severe GIM.

Patients with high-grade dysplasia or early gastric cancer should undergo endoscopic submucosal dissection (ESD), with the goal of en bloc, R0 resection to enable accurate pathologic staging and the intent to cure. Eradicating active H pylori infection is essential — but shouldn’t delay endoscopic intervention, the authors wrote.

In addition, patients with a history of successfully resected gastric dysplasia or cancer should undergo endoscopic surveillance. Although post-ESD surveillance intervals have been suggested in other recent AGA clinical practice updates, additional data are needed, particularly for US recommendations, the authors wrote.

Although type 1 gastric carcinoids in patients with atrophic gastritis are typically indolent, especially if less than 1 cm, endoscopists may consider resecting them and should resect lesions between 1and 2 cm. Patients with lesions over 2 cm should undergo cross-sectional imaging and be referred for surgical resection, given the risk for metastasis.

 

Patient-Centered Approach

The guideline authors suggested thinking about screening and surveillance on a patient-level basis. For instance, only those who are fit for endoscopic or potentially surgical treatment should be screened for gastric cancer and continued surveillance of GPMC, they wrote. If a person is no longer fit for endoscopic or surgical treatment, whether due to life expectancy or other comorbidities, then screening should be stopped.

In addition, to achieve health equity, clinicians should take a personalized approach to assess a patient’s risk for gastric cancer and determine whether to pursue screening and surveillance, the authors wrote. Modifiable risk factors — such as tobacco use, high-salt and processed food diets, and lack of health care — should also be addressed, since most of these risk factors disproportionately affect high-risk patients and represent healthcare disparities, they added.

“This update provides clinicians with a framework for understanding the natural history and epidemiology of gastric polyps, as well as guidance on best practices for the endoscopic detection and classification of gastric polyps, best practices for the endoscopic resection of gastric polyps, and best practices for endoscopic surveillance following resection,” said Hashem El-Serag, MD, professor and chair of medicine at the Baylor College of Medicine and director of the Texas Medical Center Digestive Diseases Center in Houston.

El-Serag, who wasn’t involved with the clinical practice update, has researched and published on consensus around the diagnosis and management of GIM.

“Stomach polyps are commonly found during routine endoscopic procedures. They are mostly asymptomatic and incidental, and therefore, clinicians may not be prepared ahead of time on how to deal with them,” he said. “The appropriate management requires proper identification and sampling of the polyp features and the uninvolved gastric mucosa, as well as a clear understanding of the risk factors and prognosis. Recent changes in the epidemiology and endoscopic management of gastric polyps makes this update timely and important.”

The update received no particular funding. The authors disclosed receiving grant support, having consultant relationships with, and serving in advisory roles for numerous pharmaceutical, biomedical, and biotechnology firms. Morgan and El-Serag reported having no relevant disclosures.

A version of this article appeared on Medscape.com.

In addition to healthy weight reduction through lifestyle changes, experts recommend anti-obesity medications and bariatric surgery to help manage metabolic dysfunction–associated steatotic liver disease (MASLD) in children with obesity, according to a new joint perspective paper.

Pediatric MASLD is the number-one cause of chronic liver disease in children and the number-one reason for liver transplant listing in young adults aged 18-40 years, said corresponding author Jennifer A. Panganiban, MD, Children’s Hospital of Philadelphia, Philadelphia.

The paper, published in Obesity Pillars, represents “a call to action that has been long overdue,” Panganiban told GI & Hepatology News.

The goal of the authors was to bring global awareness to the recent changes in the pediatric MASLD landscape — especially in medication use — and to empower clinicians treating the disease, she explained.

The recommendations are based on a combination of the latest published evidence and clinical expertise from eight hepatologists/gastroenterologists and two physicians from the Obesity Medicine Association, Centennial, Colorado.

One of the major barriers to MASLD management in children is suboptimal screening resulting in underdiagnosis, said Panganiban. “Unfortunately, only up to 30% of children are being screened in their pediatrician’s office.”

The new guideline outlines the patient care process from screening, referral to a subspecialist, and workup; however, the primary focus is on treatment with medication options that were previously not available or underutilized, she said.

 

Successful and Sustainable Weight Loss

Adiposity and weight gain make MASLD worse, but weight reduction has been shown to improve the condition, the authors noted. Previous strategies for curbing MASLD in children with obesity have focused mainly on lifestyle changes, but with limited success.

Nevertheless, the authors recommend continuing physical activity and nutrition as treatments for MASLD in children, with a plan tailored specifically to the patient.

In addition, however, they suggest that anti-obesity medications started early in the disease may help reduce costs and improve future outcomes.

Although glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have not yet been studied specifically for pediatric MASLD, data from studies of pediatric obesity, diabetes, and other retrospective studies are encouraging, the authors wrote.

The GLP-1 RAs liraglutide and semaglutide are both approved by the US Food and Drug Administration (FDA) for managing obesity in children and adolescents aged 12 years or older, they noted. And a recent phase 3a randomized trial showed that liraglutide, not yet approved for children younger than 12 years, led to a mean change in body mass index of 5.8% from baseline to 56 weeks in children aged 6-11 years with obesity.

GLP-1 RAs not only are effective for weight management but also improve other metabolic dysfunction indicators including cholesterol and blood pressure, which makes these medications an even more beneficial option for individuals with obesity and MASLD, Panganiban and colleagues wrote.

For example, a recent single-center study of 111 children with MASLD (mean age, 15 years) showed a significant improvement in alanine aminotransferase levels with the use of GLP-1 RAs, although body mass index and weight were unchanged.

Regaining weight after discontinuing GLP-1 RAs is the main barrier to their use for MASLD, the authors noted. In addition, GLP-1 RAs are contraindicated in some situations, such as in those with a history of serious hypersensitivity, and in patients with a personal or family history of either medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 based on animal studies showing an association with the medications and thyroid C–cell tumors.

Other FDA-approved medication options for obesity in children include metformin, topiramate, and phentermine, as well as bupropion, lisdexamfetamine, and setmelanotide, the authors said.

Resmetirom, a thyroid hormone receptor-beta agonist, which is another significant breakthrough in MASLD for adults, has not yet been tested or approved for pediatric use.

In addition to medications, metabolic bariatric surgery has shown effectiveness in children with obesity and/or MASLD by reducing liver fat and reversing fibrosis, as shown in the Teen-LABS study, the authors wrote. However, long-term data on fibrosis reversal are limited, and cost and access remain barriers.

 

More Research Needed

The joint expert review is intended as an educational tool that may require updates and should not be interpreted as rules for individual patient care, the authors cautioned. And physical activity and nutrition remain the primary treatment of MASLD and should be continued in conjunction with other treatment modalities, they emphasized.

Looking ahead, research is needed to develop accurate and reliable noninvasive biomarkers to diagnose and assess obesity treatment efficacy, Panganiban told GI & Hepatology News.

Also needed are multicenter randomized control trials in children with obesity involving different medications that have been successful in the treatment of metabolic dysfunction–associated steatohepatitis/fibrosis in adults, such as GLP-1 RAs or resmetirom, she added.

 

Educating Clinicians on Early Identification

When obesity occurs in childhood, it starts a process of additional complications that arise in earlier ages in adults, said Saul J. Karpen, MD, chief scientific officer at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia, in an interview.“Given the epidemic of obesity, altered diets, and reduced physical activities during younger ages, it is not easy to identify which children are at greater risk of MASLD,” said Karpen.

“It requires insight from the care providers and often imaging, a blood test, or a referral to a pediatric hepatologist, and not every region has easy access to such expertise,” Karpen said.

The new review is important because it highlights the fact that obesity and its consequences are not limited to adulthood, and that educated clinicians are in a position to get an early start on treatment in children, Karpen noted.

The guideline received no outside funding. Panganiban and Karpen had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

In addition to healthy weight reduction through lifestyle changes, experts recommend anti-obesity medications and bariatric surgery to help manage metabolic dysfunction–associated steatotic liver disease (MASLD) in children with obesity, according to a new joint perspective paper.

Pediatric MASLD is the number-one cause of chronic liver disease in children and the number-one reason for liver transplant listing in young adults aged 18-40 years, said corresponding author Jennifer A. Panganiban, MD, Children’s Hospital of Philadelphia, Philadelphia.

The paper, published in Obesity Pillars, represents “a call to action that has been long overdue,” Panganiban told GI & Hepatology News.

The goal of the authors was to bring global awareness to the recent changes in the pediatric MASLD landscape — especially in medication use — and to empower clinicians treating the disease, she explained.

The recommendations are based on a combination of the latest published evidence and clinical expertise from eight hepatologists/gastroenterologists and two physicians from the Obesity Medicine Association, Centennial, Colorado.

One of the major barriers to MASLD management in children is suboptimal screening resulting in underdiagnosis, said Panganiban. “Unfortunately, only up to 30% of children are being screened in their pediatrician’s office.”

The new guideline outlines the patient care process from screening, referral to a subspecialist, and workup; however, the primary focus is on treatment with medication options that were previously not available or underutilized, she said.

 

Successful and Sustainable Weight Loss

Adiposity and weight gain make MASLD worse, but weight reduction has been shown to improve the condition, the authors noted. Previous strategies for curbing MASLD in children with obesity have focused mainly on lifestyle changes, but with limited success.

Nevertheless, the authors recommend continuing physical activity and nutrition as treatments for MASLD in children, with a plan tailored specifically to the patient.

In addition, however, they suggest that anti-obesity medications started early in the disease may help reduce costs and improve future outcomes.

Although glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have not yet been studied specifically for pediatric MASLD, data from studies of pediatric obesity, diabetes, and other retrospective studies are encouraging, the authors wrote.

The GLP-1 RAs liraglutide and semaglutide are both approved by the US Food and Drug Administration (FDA) for managing obesity in children and adolescents aged 12 years or older, they noted. And a recent phase 3a randomized trial showed that liraglutide, not yet approved for children younger than 12 years, led to a mean change in body mass index of 5.8% from baseline to 56 weeks in children aged 6-11 years with obesity.

GLP-1 RAs not only are effective for weight management but also improve other metabolic dysfunction indicators including cholesterol and blood pressure, which makes these medications an even more beneficial option for individuals with obesity and MASLD, Panganiban and colleagues wrote.

For example, a recent single-center study of 111 children with MASLD (mean age, 15 years) showed a significant improvement in alanine aminotransferase levels with the use of GLP-1 RAs, although body mass index and weight were unchanged.

Regaining weight after discontinuing GLP-1 RAs is the main barrier to their use for MASLD, the authors noted. In addition, GLP-1 RAs are contraindicated in some situations, such as in those with a history of serious hypersensitivity, and in patients with a personal or family history of either medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 based on animal studies showing an association with the medications and thyroid C–cell tumors.

Other FDA-approved medication options for obesity in children include metformin, topiramate, and phentermine, as well as bupropion, lisdexamfetamine, and setmelanotide, the authors said.

Resmetirom, a thyroid hormone receptor-beta agonist, which is another significant breakthrough in MASLD for adults, has not yet been tested or approved for pediatric use.

In addition to medications, metabolic bariatric surgery has shown effectiveness in children with obesity and/or MASLD by reducing liver fat and reversing fibrosis, as shown in the Teen-LABS study, the authors wrote. However, long-term data on fibrosis reversal are limited, and cost and access remain barriers.

 

More Research Needed

The joint expert review is intended as an educational tool that may require updates and should not be interpreted as rules for individual patient care, the authors cautioned. And physical activity and nutrition remain the primary treatment of MASLD and should be continued in conjunction with other treatment modalities, they emphasized.

Looking ahead, research is needed to develop accurate and reliable noninvasive biomarkers to diagnose and assess obesity treatment efficacy, Panganiban told GI & Hepatology News.

Also needed are multicenter randomized control trials in children with obesity involving different medications that have been successful in the treatment of metabolic dysfunction–associated steatohepatitis/fibrosis in adults, such as GLP-1 RAs or resmetirom, she added.

 

Educating Clinicians on Early Identification

When obesity occurs in childhood, it starts a process of additional complications that arise in earlier ages in adults, said Saul J. Karpen, MD, chief scientific officer at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia, in an interview.“Given the epidemic of obesity, altered diets, and reduced physical activities during younger ages, it is not easy to identify which children are at greater risk of MASLD,” said Karpen.

“It requires insight from the care providers and often imaging, a blood test, or a referral to a pediatric hepatologist, and not every region has easy access to such expertise,” Karpen said.

The new review is important because it highlights the fact that obesity and its consequences are not limited to adulthood, and that educated clinicians are in a position to get an early start on treatment in children, Karpen noted.

The guideline received no outside funding. Panganiban and Karpen had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

In addition to healthy weight reduction through lifestyle changes, experts recommend anti-obesity medications and bariatric surgery to help manage metabolic dysfunction–associated steatotic liver disease (MASLD) in children with obesity, according to a new joint perspective paper.

Pediatric MASLD is the number-one cause of chronic liver disease in children and the number-one reason for liver transplant listing in young adults aged 18-40 years, said corresponding author Jennifer A. Panganiban, MD, Children’s Hospital of Philadelphia, Philadelphia.

The paper, published in Obesity Pillars, represents “a call to action that has been long overdue,” Panganiban told GI & Hepatology News.

The goal of the authors was to bring global awareness to the recent changes in the pediatric MASLD landscape — especially in medication use — and to empower clinicians treating the disease, she explained.

The recommendations are based on a combination of the latest published evidence and clinical expertise from eight hepatologists/gastroenterologists and two physicians from the Obesity Medicine Association, Centennial, Colorado.

One of the major barriers to MASLD management in children is suboptimal screening resulting in underdiagnosis, said Panganiban. “Unfortunately, only up to 30% of children are being screened in their pediatrician’s office.”

The new guideline outlines the patient care process from screening, referral to a subspecialist, and workup; however, the primary focus is on treatment with medication options that were previously not available or underutilized, she said.

 

Successful and Sustainable Weight Loss

Adiposity and weight gain make MASLD worse, but weight reduction has been shown to improve the condition, the authors noted. Previous strategies for curbing MASLD in children with obesity have focused mainly on lifestyle changes, but with limited success.

Nevertheless, the authors recommend continuing physical activity and nutrition as treatments for MASLD in children, with a plan tailored specifically to the patient.

In addition, however, they suggest that anti-obesity medications started early in the disease may help reduce costs and improve future outcomes.

Although glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have not yet been studied specifically for pediatric MASLD, data from studies of pediatric obesity, diabetes, and other retrospective studies are encouraging, the authors wrote.

The GLP-1 RAs liraglutide and semaglutide are both approved by the US Food and Drug Administration (FDA) for managing obesity in children and adolescents aged 12 years or older, they noted. And a recent phase 3a randomized trial showed that liraglutide, not yet approved for children younger than 12 years, led to a mean change in body mass index of 5.8% from baseline to 56 weeks in children aged 6-11 years with obesity.

GLP-1 RAs not only are effective for weight management but also improve other metabolic dysfunction indicators including cholesterol and blood pressure, which makes these medications an even more beneficial option for individuals with obesity and MASLD, Panganiban and colleagues wrote.

For example, a recent single-center study of 111 children with MASLD (mean age, 15 years) showed a significant improvement in alanine aminotransferase levels with the use of GLP-1 RAs, although body mass index and weight were unchanged.

Regaining weight after discontinuing GLP-1 RAs is the main barrier to their use for MASLD, the authors noted. In addition, GLP-1 RAs are contraindicated in some situations, such as in those with a history of serious hypersensitivity, and in patients with a personal or family history of either medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 based on animal studies showing an association with the medications and thyroid C–cell tumors.

Other FDA-approved medication options for obesity in children include metformin, topiramate, and phentermine, as well as bupropion, lisdexamfetamine, and setmelanotide, the authors said.

Resmetirom, a thyroid hormone receptor-beta agonist, which is another significant breakthrough in MASLD for adults, has not yet been tested or approved for pediatric use.

In addition to medications, metabolic bariatric surgery has shown effectiveness in children with obesity and/or MASLD by reducing liver fat and reversing fibrosis, as shown in the Teen-LABS study, the authors wrote. However, long-term data on fibrosis reversal are limited, and cost and access remain barriers.

 

More Research Needed

The joint expert review is intended as an educational tool that may require updates and should not be interpreted as rules for individual patient care, the authors cautioned. And physical activity and nutrition remain the primary treatment of MASLD and should be continued in conjunction with other treatment modalities, they emphasized.

Looking ahead, research is needed to develop accurate and reliable noninvasive biomarkers to diagnose and assess obesity treatment efficacy, Panganiban told GI & Hepatology News.

Also needed are multicenter randomized control trials in children with obesity involving different medications that have been successful in the treatment of metabolic dysfunction–associated steatohepatitis/fibrosis in adults, such as GLP-1 RAs or resmetirom, she added.

 

Educating Clinicians on Early Identification

When obesity occurs in childhood, it starts a process of additional complications that arise in earlier ages in adults, said Saul J. Karpen, MD, chief scientific officer at the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University, Richmond, Virginia, in an interview.“Given the epidemic of obesity, altered diets, and reduced physical activities during younger ages, it is not easy to identify which children are at greater risk of MASLD,” said Karpen.

“It requires insight from the care providers and often imaging, a blood test, or a referral to a pediatric hepatologist, and not every region has easy access to such expertise,” Karpen said.

The new review is important because it highlights the fact that obesity and its consequences are not limited to adulthood, and that educated clinicians are in a position to get an early start on treatment in children, Karpen noted.

The guideline received no outside funding. Panganiban and Karpen had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Both endoscopic ultrasound–guided rendezvous (EUS-RV) and precut sphincterotomy are equally effective salvage techniques for patients with benign biliary obstruction and difficult bile duct cannulation, new data suggest.

Selective deep cannulation of the common bile duct remains the key rate-limiting step in successful endoscopic retrograde cholangiopancreatography (ERCP), especially in benign biliary disease.

In cases of difficult cannulation, the traditional fallback has been precut sphincterotomy. Recently, EUS-RV has emerged as an alternative. However, head-to-head comparisons of these salvage techniques in homogeneous patient populations have been lacking, until now. 

A team led by Arup Choudhury, MD, DM, with Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, compared the two salvage techniques in a single-center, randomized controlled trial of 100 patients with benign biliary disease and difficult bile duct cannulation.

There were 50 patients in each group. When one technique failed, patients were crossed over to the other technique.

The technical success rate for achieving deep biliary, the primary outcome measure, was similar with EUS-RV and precut sphincterotomy (92% and 90%, respectively; P = 1.00; relative risk [RR], 1.02), the authors reported in Annals of Internal Medicine.

Median procedure time was also comparable (10.1 minutes with EUS-RV and 9.75 minutes with precut sphincterotomy). As expected, radiation exposure was notably higher in the EUS-RV group (median, 200.2 vs 67.8 mGy).

There was no difference in overall complication rates (12% and 10%, respectively; RR, 1.20).

Five patients in each group (10%) developed post-ERCP pancreatitis (PEP); one patient in the EUS-RV had moderately severe pancreatitis, whereas the rest had mild pancreatitis.

In an exploratory analysis of the subcohort of 72 patients who did not have 1 or more inadvertent pancreatic duct cannulation, two (5.6%) patients in the precut sphincterotomy group had PEP, whereas none of the patients in the EUS-RV had PEP (RR, 0.21). The investigators caution that a larger, multicenter, randomized controlled trial would be required to evaluate the “probable benefit” of lower PEP in the EUS-RV approach.

None of the patients had bleeding or perforation, but two (4%) patients in the EUS-RV group had an infection after the intervention. One required repeated ERCP due to post procedure cholangitis, whereas the other developed lower respiratory tract infection with transient acute lung injury and sputum showing gram-negative organism. None of the patients required surgical intervention.

“Interestingly,” said the investigators, on crossover from one salvage technique to the other, all of the cases could be successfully cannulated, suggesting the two salvage techniques are “complementary to each other and can help achieve successful cannulation in all cases when used in any sequence.”

Summing up, they said it appears from this head-to-head comparison that both EUS-RV and precut sphincterotomy can be considered effective salvage techniques in expert centers with similar safety and success profiles.

Limitations included the single-center design with both procedures performed by expert operators. EUS-RV entailed additional cost of needle and use of a separate scope, and a cost-efficacy analysis was not done.

This study had no specific funding. Disclosures for the authors are available with the original article.

A version of this article appeared on Medscape.com.

Both endoscopic ultrasound–guided rendezvous (EUS-RV) and precut sphincterotomy are equally effective salvage techniques for patients with benign biliary obstruction and difficult bile duct cannulation, new data suggest.

Selective deep cannulation of the common bile duct remains the key rate-limiting step in successful endoscopic retrograde cholangiopancreatography (ERCP), especially in benign biliary disease.

In cases of difficult cannulation, the traditional fallback has been precut sphincterotomy. Recently, EUS-RV has emerged as an alternative. However, head-to-head comparisons of these salvage techniques in homogeneous patient populations have been lacking, until now. 

A team led by Arup Choudhury, MD, DM, with Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, compared the two salvage techniques in a single-center, randomized controlled trial of 100 patients with benign biliary disease and difficult bile duct cannulation.

There were 50 patients in each group. When one technique failed, patients were crossed over to the other technique.

The technical success rate for achieving deep biliary, the primary outcome measure, was similar with EUS-RV and precut sphincterotomy (92% and 90%, respectively; P = 1.00; relative risk [RR], 1.02), the authors reported in Annals of Internal Medicine.

Median procedure time was also comparable (10.1 minutes with EUS-RV and 9.75 minutes with precut sphincterotomy). As expected, radiation exposure was notably higher in the EUS-RV group (median, 200.2 vs 67.8 mGy).

There was no difference in overall complication rates (12% and 10%, respectively; RR, 1.20).

Five patients in each group (10%) developed post-ERCP pancreatitis (PEP); one patient in the EUS-RV had moderately severe pancreatitis, whereas the rest had mild pancreatitis.

In an exploratory analysis of the subcohort of 72 patients who did not have 1 or more inadvertent pancreatic duct cannulation, two (5.6%) patients in the precut sphincterotomy group had PEP, whereas none of the patients in the EUS-RV had PEP (RR, 0.21). The investigators caution that a larger, multicenter, randomized controlled trial would be required to evaluate the “probable benefit” of lower PEP in the EUS-RV approach.

None of the patients had bleeding or perforation, but two (4%) patients in the EUS-RV group had an infection after the intervention. One required repeated ERCP due to post procedure cholangitis, whereas the other developed lower respiratory tract infection with transient acute lung injury and sputum showing gram-negative organism. None of the patients required surgical intervention.

“Interestingly,” said the investigators, on crossover from one salvage technique to the other, all of the cases could be successfully cannulated, suggesting the two salvage techniques are “complementary to each other and can help achieve successful cannulation in all cases when used in any sequence.”

Summing up, they said it appears from this head-to-head comparison that both EUS-RV and precut sphincterotomy can be considered effective salvage techniques in expert centers with similar safety and success profiles.

Limitations included the single-center design with both procedures performed by expert operators. EUS-RV entailed additional cost of needle and use of a separate scope, and a cost-efficacy analysis was not done.

This study had no specific funding. Disclosures for the authors are available with the original article.

A version of this article appeared on Medscape.com.

Both endoscopic ultrasound–guided rendezvous (EUS-RV) and precut sphincterotomy are equally effective salvage techniques for patients with benign biliary obstruction and difficult bile duct cannulation, new data suggest.

Selective deep cannulation of the common bile duct remains the key rate-limiting step in successful endoscopic retrograde cholangiopancreatography (ERCP), especially in benign biliary disease.

In cases of difficult cannulation, the traditional fallback has been precut sphincterotomy. Recently, EUS-RV has emerged as an alternative. However, head-to-head comparisons of these salvage techniques in homogeneous patient populations have been lacking, until now. 

A team led by Arup Choudhury, MD, DM, with Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, compared the two salvage techniques in a single-center, randomized controlled trial of 100 patients with benign biliary disease and difficult bile duct cannulation.

There were 50 patients in each group. When one technique failed, patients were crossed over to the other technique.

The technical success rate for achieving deep biliary, the primary outcome measure, was similar with EUS-RV and precut sphincterotomy (92% and 90%, respectively; P = 1.00; relative risk [RR], 1.02), the authors reported in Annals of Internal Medicine.

Median procedure time was also comparable (10.1 minutes with EUS-RV and 9.75 minutes with precut sphincterotomy). As expected, radiation exposure was notably higher in the EUS-RV group (median, 200.2 vs 67.8 mGy).

There was no difference in overall complication rates (12% and 10%, respectively; RR, 1.20).

Five patients in each group (10%) developed post-ERCP pancreatitis (PEP); one patient in the EUS-RV had moderately severe pancreatitis, whereas the rest had mild pancreatitis.

In an exploratory analysis of the subcohort of 72 patients who did not have 1 or more inadvertent pancreatic duct cannulation, two (5.6%) patients in the precut sphincterotomy group had PEP, whereas none of the patients in the EUS-RV had PEP (RR, 0.21). The investigators caution that a larger, multicenter, randomized controlled trial would be required to evaluate the “probable benefit” of lower PEP in the EUS-RV approach.

None of the patients had bleeding or perforation, but two (4%) patients in the EUS-RV group had an infection after the intervention. One required repeated ERCP due to post procedure cholangitis, whereas the other developed lower respiratory tract infection with transient acute lung injury and sputum showing gram-negative organism. None of the patients required surgical intervention.

“Interestingly,” said the investigators, on crossover from one salvage technique to the other, all of the cases could be successfully cannulated, suggesting the two salvage techniques are “complementary to each other and can help achieve successful cannulation in all cases when used in any sequence.”

Summing up, they said it appears from this head-to-head comparison that both EUS-RV and precut sphincterotomy can be considered effective salvage techniques in expert centers with similar safety and success profiles.

Limitations included the single-center design with both procedures performed by expert operators. EUS-RV entailed additional cost of needle and use of a separate scope, and a cost-efficacy analysis was not done.

This study had no specific funding. Disclosures for the authors are available with the original article.

A version of this article appeared on Medscape.com.