GI and Hepatology News

Happy New Year, everyone! As we enter 2025, I’ve been reflecting on just how much has changed in the field of gastroenterology since I completed my fellowship a decade ago.

After developing and disseminating highly effective treatments for hepatitis C, the field of hepatology has shifted rapidly toward identifying and managing other significant causes of liver disease, particularly alcohol-associated liver disease and metabolic dysfunction–associated steatotic liver disease (MASLD). New disease nomenclatures have been developed that have changed the way we describe common diseases – most notably, NALFD is now MASLD and FGID are now DGBI.

There have been marked advances in obesity management, including not only innovations in endobariatric therapies such as intragastric balloons and endoscopic sleeve gastroplasty, but also the introduction of glucagon-like peptide 1 (GLP-1) agonists, which offer new hope in effectively tackling the obesity epidemic. Our growing understanding of the microbiome’s role in health has opened new avenues for treating GI diseases and introduced the potential for more personalized treatment approaches based on individual microbiome profiles. New inflammatory bowel disease (IBD) pharmacotherapeutics have been developed at a dizzying pace – our IBD patients have so many more treatment options today than they did just a decade ago, making treatment decisions much more complex.

Finally, we are just beginning to unleash the potential of artificial intelligence, which is likely to transform the field of medicine and GI clinical practice over the next decade. To be sure, it is an exciting time to be a gastroenterologist, and I can’t wait to see to what the next decade of innovation and discovery will bring.

In this month’s issue of GI & Hepatology News, we highlight the first-ever “living” AGA clinical practice guideline on pharmacologic management of moderate to severe ulcerative colitis. From the recent AASLD meeting, we bring you exciting new data demonstrating the effectiveness of GLP-1 agonists (specifically, semaglutide) in treating MASH. In January’s Member Spotlight column, we introduce you to Drs. Mindy, Amy, and Kristen Engevik, who share their fascinating career journeys as GI researchers (and sisters!). In our quarterly Perspectives column, Dr. Brijesh Patel and Dr. Gomez Cifuentes share their experiences counseling patients regarding lifestyle modifications for gastroesophageal reflux disease and what strategies have proven to be the most effective adjuncts to pharmacotherapy. We hope you enjoy this and all the exciting content in our January issue.

Megan A. Adams, MD, JD, MSc

Editor in Chief

Happy New Year, everyone! As we enter 2025, I’ve been reflecting on just how much has changed in the field of gastroenterology since I completed my fellowship a decade ago.

After developing and disseminating highly effective treatments for hepatitis C, the field of hepatology has shifted rapidly toward identifying and managing other significant causes of liver disease, particularly alcohol-associated liver disease and metabolic dysfunction–associated steatotic liver disease (MASLD). New disease nomenclatures have been developed that have changed the way we describe common diseases – most notably, NALFD is now MASLD and FGID are now DGBI.

There have been marked advances in obesity management, including not only innovations in endobariatric therapies such as intragastric balloons and endoscopic sleeve gastroplasty, but also the introduction of glucagon-like peptide 1 (GLP-1) agonists, which offer new hope in effectively tackling the obesity epidemic. Our growing understanding of the microbiome’s role in health has opened new avenues for treating GI diseases and introduced the potential for more personalized treatment approaches based on individual microbiome profiles. New inflammatory bowel disease (IBD) pharmacotherapeutics have been developed at a dizzying pace – our IBD patients have so many more treatment options today than they did just a decade ago, making treatment decisions much more complex.

Finally, we are just beginning to unleash the potential of artificial intelligence, which is likely to transform the field of medicine and GI clinical practice over the next decade. To be sure, it is an exciting time to be a gastroenterologist, and I can’t wait to see to what the next decade of innovation and discovery will bring.

In this month’s issue of GI & Hepatology News, we highlight the first-ever “living” AGA clinical practice guideline on pharmacologic management of moderate to severe ulcerative colitis. From the recent AASLD meeting, we bring you exciting new data demonstrating the effectiveness of GLP-1 agonists (specifically, semaglutide) in treating MASH. In January’s Member Spotlight column, we introduce you to Drs. Mindy, Amy, and Kristen Engevik, who share their fascinating career journeys as GI researchers (and sisters!). In our quarterly Perspectives column, Dr. Brijesh Patel and Dr. Gomez Cifuentes share their experiences counseling patients regarding lifestyle modifications for gastroesophageal reflux disease and what strategies have proven to be the most effective adjuncts to pharmacotherapy. We hope you enjoy this and all the exciting content in our January issue.

Megan A. Adams, MD, JD, MSc

Editor in Chief

Happy New Year, everyone! As we enter 2025, I’ve been reflecting on just how much has changed in the field of gastroenterology since I completed my fellowship a decade ago.

After developing and disseminating highly effective treatments for hepatitis C, the field of hepatology has shifted rapidly toward identifying and managing other significant causes of liver disease, particularly alcohol-associated liver disease and metabolic dysfunction–associated steatotic liver disease (MASLD). New disease nomenclatures have been developed that have changed the way we describe common diseases – most notably, NALFD is now MASLD and FGID are now DGBI.

There have been marked advances in obesity management, including not only innovations in endobariatric therapies such as intragastric balloons and endoscopic sleeve gastroplasty, but also the introduction of glucagon-like peptide 1 (GLP-1) agonists, which offer new hope in effectively tackling the obesity epidemic. Our growing understanding of the microbiome’s role in health has opened new avenues for treating GI diseases and introduced the potential for more personalized treatment approaches based on individual microbiome profiles. New inflammatory bowel disease (IBD) pharmacotherapeutics have been developed at a dizzying pace – our IBD patients have so many more treatment options today than they did just a decade ago, making treatment decisions much more complex.

Finally, we are just beginning to unleash the potential of artificial intelligence, which is likely to transform the field of medicine and GI clinical practice over the next decade. To be sure, it is an exciting time to be a gastroenterologist, and I can’t wait to see to what the next decade of innovation and discovery will bring.

In this month’s issue of GI & Hepatology News, we highlight the first-ever “living” AGA clinical practice guideline on pharmacologic management of moderate to severe ulcerative colitis. From the recent AASLD meeting, we bring you exciting new data demonstrating the effectiveness of GLP-1 agonists (specifically, semaglutide) in treating MASH. In January’s Member Spotlight column, we introduce you to Drs. Mindy, Amy, and Kristen Engevik, who share their fascinating career journeys as GI researchers (and sisters!). In our quarterly Perspectives column, Dr. Brijesh Patel and Dr. Gomez Cifuentes share their experiences counseling patients regarding lifestyle modifications for gastroesophageal reflux disease and what strategies have proven to be the most effective adjuncts to pharmacotherapy. We hope you enjoy this and all the exciting content in our January issue.

Megan A. Adams, MD, JD, MSc

Editor in Chief

International researchers have uncovered potentially diagnostic gut microbiome signatures and metabolic pathways associated specifically with ulcerative colitis (UC) and Crohn’s disease (CD).

Targeted droplet digital polymerase chain reaction (ddPCR)‒based quantification of bacterial species led to convenient inflammatory bowel disease (IBD) diagnostic assays that “are sufficiently robust, sensitive and cost-effective for clinical application,” the investigators wrote in a recent study published in Nature Medicine.

“Although traditional modalities used for diagnosis of IBD, including colonoscopy and cross-sectional imaging, are well established, the inconvenience of bowel preparation and radiation represents relevant concerns,” senior author Siew C. Ng, MBBS, PhD, a professor in the Department of Medicine and Therapeutics at the Chinese University of Hong Kong, said in an interview. “Furthermore, existing serological and fecal markers indicate inflammation but lack specificity for IBD.”

Identifying reproducible bacterial biomarkers specific to CD and IBD should enable precise and personalized approaches to detection and management.

As a starting point, the researchers hypothesized that changes in the gut microbiome of IBD patients may reflect underlying functional associations, if not causes, of the disease, said Ng, who is also director of Hong Kong’s Microbiota I-Center (MagIC). “Unlike inflammation, which is a manifestation of the disease, the gut microbiome may serve as a more reliable biomarker less affected by the disease’s fluctuating cycle.”

The study findings showed that bacterial markers remain consistent even during the inactive disease phase. Additionally, the results are reproducible across different populations, suggesting that these markers are true indicators of IBD, she added. “With a better performance than the commonly used noninvasive test, fecal calprotectin, we believe the test will be a valuable addition to clinician’s toolbox and a strong option for first-line diagnostics.”

 

The Study

The group used metagenomic data from 5979 fecal samples from persons with and without IBD from different regions (including the United States) and of different ethnicities. Identifying several microbiota alterations in IBD, they selected bacterial species to construct diagnostic models for UC (n = 10) and CD (n = 9). Some species were deleted and some were enriched in IBD.

Metagenomic findings confirmed, for example, enrichments of Escherichia coli and Bacteroides fragilis in the guts of CD patients, with adherent invasive E coli present in more than half of these. This pathogen has been linked to mucosal dysbiosis and functional alteration, and has been associated with disease activity and endoscopic recurrence following surgery. B fragilis may induce intestinal inflammation through toxin production.

The researchers also identified a new oral bacterium, Actinomyces species oral taxon 181, which was significantly enriched in stool samples with both CD and UC.

The diagnostic models achieved areas under the curve of >.90 for distinguishing IBD patients from controls in the discovery cohort and maintained satisfactory performance in transethnic validation cohorts from eight populations.

Ng’s group further developed a multiplex droplet digital PCR test targeting selected IBD-associated bacterial species. Models based on this test showed numerically higher performance than fecal calprotectin in discriminating UC and CD samples from controls. These universally IBD-associated bacteria suggest the potential applicability of a biomarker panel for noninvasive diagnosis.

Commenting on the paper but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston and associate professor of medicine at Harvard Medical School, called it “a very important study that highlights the potential role of a microbiome-based diagnostic for screening. It could have application in a wide variety of settings and is very promising.”

More work, however, is necessary to clarify such testing’s role. “The study’s validation in independent cohorts is an important strength, but the sizes of those cohorts are still quite small,” he said in an interview. “It’s important to understand its accuracy across a spectrum of IBD phenotypes and severity.”

Furthermore, endoscopic evaluation at diagnosis is important to establish severity and extent of disease. “It’s not clear this diagnostic biomarker can help supplant that role. But I see potential value to it for patients for whom we may not be considering endoscopy yet but who would like to risk-stratify.”

 

The Test’s Future

“We expect to see a real shift in clinical practice,” Ng said. “As a cost-effective test, it will help millions of people dealing with nonspecific gastrointestinal symptoms get the diagnoses they need.” Because the bacterial test can identify IBD at an inactive stage, it has the potential for early diagnosis. “This capability allows clinicians to initiate treatment sooner, helping to prevent progression from subclinical to clinical stages of the disease.”

The next research steps involve prospective studies with a larger and more diverse group of patients with various gastrointestinal symptoms. “This will enable a comprehensive evaluation of bacterial biomarkers in real-world populations,” she said. In vivo and in vitro experiments are expected to provide mechanistic insights into the causal role of these bacteria and metabolic dysregulations in the pathogenesis of IBD, as well as their future clinical utility in disease monitoring and predicting treatment response.

Her group plans to work with the biotech industry and regulatory agencies to transform these biomarkers into an approved test kit. “The rollout is likely to be gradual, but we’re optimistic that supportive international and national guidelines will be developed and will pave the way for widespread implementation.”

This study was supported by various academic, charitable, and governmental research-funding bodies, including the governments of Hong Kong and the People’s Republic of China. Ng has served as an advisory board member or speaker for Pfizer, Ferring, Janssen, AbbVie, Tillotts, Menarini, and Takeda. She has received research grants through her institutions from Olympus, Ferring, and AbbVie and is a founding member and shareholder of GenieBiome. She receives patent royalties through her institutions, including MagIC, which holds patents on the therapeutic and diagnostic use of the microbiome in IBD. Several co-authors reported various relationships, including patent holding, with private-sector companies. Ananthakrishnan had no relevant competing interests.

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

International researchers have uncovered potentially diagnostic gut microbiome signatures and metabolic pathways associated specifically with ulcerative colitis (UC) and Crohn’s disease (CD).

Targeted droplet digital polymerase chain reaction (ddPCR)‒based quantification of bacterial species led to convenient inflammatory bowel disease (IBD) diagnostic assays that “are sufficiently robust, sensitive and cost-effective for clinical application,” the investigators wrote in a recent study published in Nature Medicine.

“Although traditional modalities used for diagnosis of IBD, including colonoscopy and cross-sectional imaging, are well established, the inconvenience of bowel preparation and radiation represents relevant concerns,” senior author Siew C. Ng, MBBS, PhD, a professor in the Department of Medicine and Therapeutics at the Chinese University of Hong Kong, said in an interview. “Furthermore, existing serological and fecal markers indicate inflammation but lack specificity for IBD.”

Identifying reproducible bacterial biomarkers specific to CD and IBD should enable precise and personalized approaches to detection and management.

As a starting point, the researchers hypothesized that changes in the gut microbiome of IBD patients may reflect underlying functional associations, if not causes, of the disease, said Ng, who is also director of Hong Kong’s Microbiota I-Center (MagIC). “Unlike inflammation, which is a manifestation of the disease, the gut microbiome may serve as a more reliable biomarker less affected by the disease’s fluctuating cycle.”

The study findings showed that bacterial markers remain consistent even during the inactive disease phase. Additionally, the results are reproducible across different populations, suggesting that these markers are true indicators of IBD, she added. “With a better performance than the commonly used noninvasive test, fecal calprotectin, we believe the test will be a valuable addition to clinician’s toolbox and a strong option for first-line diagnostics.”

 

The Study

The group used metagenomic data from 5979 fecal samples from persons with and without IBD from different regions (including the United States) and of different ethnicities. Identifying several microbiota alterations in IBD, they selected bacterial species to construct diagnostic models for UC (n = 10) and CD (n = 9). Some species were deleted and some were enriched in IBD.

Metagenomic findings confirmed, for example, enrichments of Escherichia coli and Bacteroides fragilis in the guts of CD patients, with adherent invasive E coli present in more than half of these. This pathogen has been linked to mucosal dysbiosis and functional alteration, and has been associated with disease activity and endoscopic recurrence following surgery. B fragilis may induce intestinal inflammation through toxin production.

The researchers also identified a new oral bacterium, Actinomyces species oral taxon 181, which was significantly enriched in stool samples with both CD and UC.

The diagnostic models achieved areas under the curve of >.90 for distinguishing IBD patients from controls in the discovery cohort and maintained satisfactory performance in transethnic validation cohorts from eight populations.

Ng’s group further developed a multiplex droplet digital PCR test targeting selected IBD-associated bacterial species. Models based on this test showed numerically higher performance than fecal calprotectin in discriminating UC and CD samples from controls. These universally IBD-associated bacteria suggest the potential applicability of a biomarker panel for noninvasive diagnosis.

Commenting on the paper but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston and associate professor of medicine at Harvard Medical School, called it “a very important study that highlights the potential role of a microbiome-based diagnostic for screening. It could have application in a wide variety of settings and is very promising.”

More work, however, is necessary to clarify such testing’s role. “The study’s validation in independent cohorts is an important strength, but the sizes of those cohorts are still quite small,” he said in an interview. “It’s important to understand its accuracy across a spectrum of IBD phenotypes and severity.”

Furthermore, endoscopic evaluation at diagnosis is important to establish severity and extent of disease. “It’s not clear this diagnostic biomarker can help supplant that role. But I see potential value to it for patients for whom we may not be considering endoscopy yet but who would like to risk-stratify.”

 

The Test’s Future

“We expect to see a real shift in clinical practice,” Ng said. “As a cost-effective test, it will help millions of people dealing with nonspecific gastrointestinal symptoms get the diagnoses they need.” Because the bacterial test can identify IBD at an inactive stage, it has the potential for early diagnosis. “This capability allows clinicians to initiate treatment sooner, helping to prevent progression from subclinical to clinical stages of the disease.”

The next research steps involve prospective studies with a larger and more diverse group of patients with various gastrointestinal symptoms. “This will enable a comprehensive evaluation of bacterial biomarkers in real-world populations,” she said. In vivo and in vitro experiments are expected to provide mechanistic insights into the causal role of these bacteria and metabolic dysregulations in the pathogenesis of IBD, as well as their future clinical utility in disease monitoring and predicting treatment response.

Her group plans to work with the biotech industry and regulatory agencies to transform these biomarkers into an approved test kit. “The rollout is likely to be gradual, but we’re optimistic that supportive international and national guidelines will be developed and will pave the way for widespread implementation.”

This study was supported by various academic, charitable, and governmental research-funding bodies, including the governments of Hong Kong and the People’s Republic of China. Ng has served as an advisory board member or speaker for Pfizer, Ferring, Janssen, AbbVie, Tillotts, Menarini, and Takeda. She has received research grants through her institutions from Olympus, Ferring, and AbbVie and is a founding member and shareholder of GenieBiome. She receives patent royalties through her institutions, including MagIC, which holds patents on the therapeutic and diagnostic use of the microbiome in IBD. Several co-authors reported various relationships, including patent holding, with private-sector companies. Ananthakrishnan had no relevant competing interests.

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

International researchers have uncovered potentially diagnostic gut microbiome signatures and metabolic pathways associated specifically with ulcerative colitis (UC) and Crohn’s disease (CD).

Targeted droplet digital polymerase chain reaction (ddPCR)‒based quantification of bacterial species led to convenient inflammatory bowel disease (IBD) diagnostic assays that “are sufficiently robust, sensitive and cost-effective for clinical application,” the investigators wrote in a recent study published in Nature Medicine.

“Although traditional modalities used for diagnosis of IBD, including colonoscopy and cross-sectional imaging, are well established, the inconvenience of bowel preparation and radiation represents relevant concerns,” senior author Siew C. Ng, MBBS, PhD, a professor in the Department of Medicine and Therapeutics at the Chinese University of Hong Kong, said in an interview. “Furthermore, existing serological and fecal markers indicate inflammation but lack specificity for IBD.”

Identifying reproducible bacterial biomarkers specific to CD and IBD should enable precise and personalized approaches to detection and management.

As a starting point, the researchers hypothesized that changes in the gut microbiome of IBD patients may reflect underlying functional associations, if not causes, of the disease, said Ng, who is also director of Hong Kong’s Microbiota I-Center (MagIC). “Unlike inflammation, which is a manifestation of the disease, the gut microbiome may serve as a more reliable biomarker less affected by the disease’s fluctuating cycle.”

The study findings showed that bacterial markers remain consistent even during the inactive disease phase. Additionally, the results are reproducible across different populations, suggesting that these markers are true indicators of IBD, she added. “With a better performance than the commonly used noninvasive test, fecal calprotectin, we believe the test will be a valuable addition to clinician’s toolbox and a strong option for first-line diagnostics.”

 

The Study

The group used metagenomic data from 5979 fecal samples from persons with and without IBD from different regions (including the United States) and of different ethnicities. Identifying several microbiota alterations in IBD, they selected bacterial species to construct diagnostic models for UC (n = 10) and CD (n = 9). Some species were deleted and some were enriched in IBD.

Metagenomic findings confirmed, for example, enrichments of Escherichia coli and Bacteroides fragilis in the guts of CD patients, with adherent invasive E coli present in more than half of these. This pathogen has been linked to mucosal dysbiosis and functional alteration, and has been associated with disease activity and endoscopic recurrence following surgery. B fragilis may induce intestinal inflammation through toxin production.

The researchers also identified a new oral bacterium, Actinomyces species oral taxon 181, which was significantly enriched in stool samples with both CD and UC.

The diagnostic models achieved areas under the curve of >.90 for distinguishing IBD patients from controls in the discovery cohort and maintained satisfactory performance in transethnic validation cohorts from eight populations.

Ng’s group further developed a multiplex droplet digital PCR test targeting selected IBD-associated bacterial species. Models based on this test showed numerically higher performance than fecal calprotectin in discriminating UC and CD samples from controls. These universally IBD-associated bacteria suggest the potential applicability of a biomarker panel for noninvasive diagnosis.

Commenting on the paper but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital in Boston and associate professor of medicine at Harvard Medical School, called it “a very important study that highlights the potential role of a microbiome-based diagnostic for screening. It could have application in a wide variety of settings and is very promising.”

More work, however, is necessary to clarify such testing’s role. “The study’s validation in independent cohorts is an important strength, but the sizes of those cohorts are still quite small,” he said in an interview. “It’s important to understand its accuracy across a spectrum of IBD phenotypes and severity.”

Furthermore, endoscopic evaluation at diagnosis is important to establish severity and extent of disease. “It’s not clear this diagnostic biomarker can help supplant that role. But I see potential value to it for patients for whom we may not be considering endoscopy yet but who would like to risk-stratify.”

 

The Test’s Future

“We expect to see a real shift in clinical practice,” Ng said. “As a cost-effective test, it will help millions of people dealing with nonspecific gastrointestinal symptoms get the diagnoses they need.” Because the bacterial test can identify IBD at an inactive stage, it has the potential for early diagnosis. “This capability allows clinicians to initiate treatment sooner, helping to prevent progression from subclinical to clinical stages of the disease.”

The next research steps involve prospective studies with a larger and more diverse group of patients with various gastrointestinal symptoms. “This will enable a comprehensive evaluation of bacterial biomarkers in real-world populations,” she said. In vivo and in vitro experiments are expected to provide mechanistic insights into the causal role of these bacteria and metabolic dysregulations in the pathogenesis of IBD, as well as their future clinical utility in disease monitoring and predicting treatment response.

Her group plans to work with the biotech industry and regulatory agencies to transform these biomarkers into an approved test kit. “The rollout is likely to be gradual, but we’re optimistic that supportive international and national guidelines will be developed and will pave the way for widespread implementation.”

This study was supported by various academic, charitable, and governmental research-funding bodies, including the governments of Hong Kong and the People’s Republic of China. Ng has served as an advisory board member or speaker for Pfizer, Ferring, Janssen, AbbVie, Tillotts, Menarini, and Takeda. She has received research grants through her institutions from Olympus, Ferring, and AbbVie and is a founding member and shareholder of GenieBiome. She receives patent royalties through her institutions, including MagIC, which holds patents on the therapeutic and diagnostic use of the microbiome in IBD. Several co-authors reported various relationships, including patent holding, with private-sector companies. Ananthakrishnan had no relevant competing interests.

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

Among patients with eosinophilic esophagitis (EoE), both those who are responsive to proton pump inhibitors (PPIs) and those who are unresponsive to PPI treatment share similar esophageal protein profiles, which are distinct from those without EoE, according to comparative proteomic analyses.

Notably, after PPI therapy, the protein profiles of responsive patients reverted and appeared similar to non-EoE patients, whereas the profiles of nonresponsive patients remained largely unchanged.

“Identifying protein biomarkers associated with PPI response may help distinguish EoE phenotypes and guide therapy selections,” said senior author Walter Chan, MD, AGAF, associate professor of medicine in the Division of Gastroenterology, Hepatology, and Endoscopy at Harvard Medical School and director of the center for gastrointestinal motility at Brigham and Women’s Hospital, Boston.

“These findings may provide the framework for developing protein biomarkers to assess response to therapy and monitor disease activity,” he added.

The study was published online in Gastroenterology.

 

Comparative Proteomic Analyses

Chan and colleagues conducted a prospective exploratory pilot study to identify the differences in esophageal protein profiles among PPI-responsive-EoE (PPI-R-EoE), PPI-nonresponsive-EoE (PPI-NR-EoE), and non-EoE controls using SOMAscan, a proteomics platform that allows simultaneous detection of 1305 human proteins.

The research team prospectively enrolled patients undergoing endoscopy for esophageal symptoms or for EoE follow-up, obtaining clinically indicated biopsies as well as extra samples from the midesophagus.

Patients who were diagnosed with EoE (at 15 or greater eosinophils per high-power field, or eos/hpf) were treated with 20 mg of omeprazole twice daily for 8 weeks, followed by repeat biopsies to assess treatment response.

Patients with histologic remission (fewer than 15 eos/hpf) were classified as PPI-R-EoE, whereas those with persistently active disease were classified as PPI-NR-EoE. Patients without EoE served as controls and were categorized as having erosive esophagitis (EE) or no esophagitis.

Overall, the study enrolled 32 patients, including 15 with PPI-R-EoE, eight with PPI-NR-EoE, three with EE, and six with no esophagitis. The demographics, symptoms, and endoscopic findings were similar between the PPI-R-EoE and PPI-NR-EoE patients.

At the index endoscopy, the PPI-R-EoE and PPI-NR-EoE patients had similar esophageal protein profiles, with only 20 proteins differentially expressed at a relaxed cutoff of P < .1. An analysis of the 20 proteins predicted lower expression of six proteins that may be associated with gastrointestinal inflammation in nonresponsive patients, including STAT1, STAT3, CFB, interleukin (IL)-17RA, TNFRSF1A, and SERPINA3.

In addition, 136 proteins — including 15 with corrected P < .05 — clearly discriminated PPI-R-EoE patients from non-EoE controls, and 255 proteins — including 249 with P < .05 — discriminated PPI-NR-EoE patients from controls. Both types of EoE patients had proteins associated with enhanced inflammation and vasculogenesis, as well as down-regulation of CRISP3 and DSG1 and upregulation of TNFAIP6.

The comparative analyses also showed that the follow-up biopsies of PPI-R-EoE patients had protein profiles that resembled non-EoE controls after PPI therapy.

“This further supports the hypothesis that despite the PPI response, PPI-R-EoE represents a subtype of EoE rather than gastroesophageal reflux disease (GERD),” Chan said.

 

Future EoE Considerations

Although most expressed proteins appeared similar between PPI-responsive and nonresponsive patients before treatment, a few proteins differed related to gastrointestinal inflammation, the study authors wrote, including some previously implicated in IL4 and IL13 inflammatory pathways.

“Further study of these proteins may provide insights into the EoE pathogenic pathway, explore their potential to predict PPI response at diagnosis, and identify possible therapeutic targets,” they wrote.

The authors pointed to the small study size as the primary limitation, noting that the pilot study was intended to explore the feasibility of using SomaScan to assess esophageal protein profiles in different EoE phenotypes. In the future, larger studies with more expansive candidate proteins could help characterize the differences and better identify specific proteins and pathways in EoE, they wrote.

“The takeaway is that PPI responsiveness does not distinguish EoE from GERD but rather PPI is a primary therapy for EoE independent of GERD,” said Marc Rothenberg, MD, director of allergy and immunology and director of the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio.

Rothenberg, who wasn’t involved with this study, has conducted transcriptome analyses of PPI-R-EoE, which showed PPI-reversible allergic inflammation.

“PPI-R-EoE and PPI-NR-EoE look the same at the molecular level,” he said. “After therapy, PPI-R-EoE normalizes, as per its definition.”

This study was supported by the Campaign Urging Research for Eosinophilic Disease Foundation Grant, the Kenneth and Louise Goldberg Junior Faculty Award, and a National Institutes of Health award. Chan declared advisory board positions with several pharmaceutical companies and Rothenberg reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Among patients with eosinophilic esophagitis (EoE), both those who are responsive to proton pump inhibitors (PPIs) and those who are unresponsive to PPI treatment share similar esophageal protein profiles, which are distinct from those without EoE, according to comparative proteomic analyses.

Notably, after PPI therapy, the protein profiles of responsive patients reverted and appeared similar to non-EoE patients, whereas the profiles of nonresponsive patients remained largely unchanged.

“Identifying protein biomarkers associated with PPI response may help distinguish EoE phenotypes and guide therapy selections,” said senior author Walter Chan, MD, AGAF, associate professor of medicine in the Division of Gastroenterology, Hepatology, and Endoscopy at Harvard Medical School and director of the center for gastrointestinal motility at Brigham and Women’s Hospital, Boston.

“These findings may provide the framework for developing protein biomarkers to assess response to therapy and monitor disease activity,” he added.

The study was published online in Gastroenterology.

 

Comparative Proteomic Analyses

Chan and colleagues conducted a prospective exploratory pilot study to identify the differences in esophageal protein profiles among PPI-responsive-EoE (PPI-R-EoE), PPI-nonresponsive-EoE (PPI-NR-EoE), and non-EoE controls using SOMAscan, a proteomics platform that allows simultaneous detection of 1305 human proteins.

The research team prospectively enrolled patients undergoing endoscopy for esophageal symptoms or for EoE follow-up, obtaining clinically indicated biopsies as well as extra samples from the midesophagus.

Patients who were diagnosed with EoE (at 15 or greater eosinophils per high-power field, or eos/hpf) were treated with 20 mg of omeprazole twice daily for 8 weeks, followed by repeat biopsies to assess treatment response.

Patients with histologic remission (fewer than 15 eos/hpf) were classified as PPI-R-EoE, whereas those with persistently active disease were classified as PPI-NR-EoE. Patients without EoE served as controls and were categorized as having erosive esophagitis (EE) or no esophagitis.

Overall, the study enrolled 32 patients, including 15 with PPI-R-EoE, eight with PPI-NR-EoE, three with EE, and six with no esophagitis. The demographics, symptoms, and endoscopic findings were similar between the PPI-R-EoE and PPI-NR-EoE patients.

At the index endoscopy, the PPI-R-EoE and PPI-NR-EoE patients had similar esophageal protein profiles, with only 20 proteins differentially expressed at a relaxed cutoff of P < .1. An analysis of the 20 proteins predicted lower expression of six proteins that may be associated with gastrointestinal inflammation in nonresponsive patients, including STAT1, STAT3, CFB, interleukin (IL)-17RA, TNFRSF1A, and SERPINA3.

In addition, 136 proteins — including 15 with corrected P < .05 — clearly discriminated PPI-R-EoE patients from non-EoE controls, and 255 proteins — including 249 with P < .05 — discriminated PPI-NR-EoE patients from controls. Both types of EoE patients had proteins associated with enhanced inflammation and vasculogenesis, as well as down-regulation of CRISP3 and DSG1 and upregulation of TNFAIP6.

The comparative analyses also showed that the follow-up biopsies of PPI-R-EoE patients had protein profiles that resembled non-EoE controls after PPI therapy.

“This further supports the hypothesis that despite the PPI response, PPI-R-EoE represents a subtype of EoE rather than gastroesophageal reflux disease (GERD),” Chan said.

 

Future EoE Considerations

Although most expressed proteins appeared similar between PPI-responsive and nonresponsive patients before treatment, a few proteins differed related to gastrointestinal inflammation, the study authors wrote, including some previously implicated in IL4 and IL13 inflammatory pathways.

“Further study of these proteins may provide insights into the EoE pathogenic pathway, explore their potential to predict PPI response at diagnosis, and identify possible therapeutic targets,” they wrote.

The authors pointed to the small study size as the primary limitation, noting that the pilot study was intended to explore the feasibility of using SomaScan to assess esophageal protein profiles in different EoE phenotypes. In the future, larger studies with more expansive candidate proteins could help characterize the differences and better identify specific proteins and pathways in EoE, they wrote.

“The takeaway is that PPI responsiveness does not distinguish EoE from GERD but rather PPI is a primary therapy for EoE independent of GERD,” said Marc Rothenberg, MD, director of allergy and immunology and director of the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio.

Rothenberg, who wasn’t involved with this study, has conducted transcriptome analyses of PPI-R-EoE, which showed PPI-reversible allergic inflammation.

“PPI-R-EoE and PPI-NR-EoE look the same at the molecular level,” he said. “After therapy, PPI-R-EoE normalizes, as per its definition.”

This study was supported by the Campaign Urging Research for Eosinophilic Disease Foundation Grant, the Kenneth and Louise Goldberg Junior Faculty Award, and a National Institutes of Health award. Chan declared advisory board positions with several pharmaceutical companies and Rothenberg reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Among patients with eosinophilic esophagitis (EoE), both those who are responsive to proton pump inhibitors (PPIs) and those who are unresponsive to PPI treatment share similar esophageal protein profiles, which are distinct from those without EoE, according to comparative proteomic analyses.

Notably, after PPI therapy, the protein profiles of responsive patients reverted and appeared similar to non-EoE patients, whereas the profiles of nonresponsive patients remained largely unchanged.

“Identifying protein biomarkers associated with PPI response may help distinguish EoE phenotypes and guide therapy selections,” said senior author Walter Chan, MD, AGAF, associate professor of medicine in the Division of Gastroenterology, Hepatology, and Endoscopy at Harvard Medical School and director of the center for gastrointestinal motility at Brigham and Women’s Hospital, Boston.

“These findings may provide the framework for developing protein biomarkers to assess response to therapy and monitor disease activity,” he added.

The study was published online in Gastroenterology.

 

Comparative Proteomic Analyses

Chan and colleagues conducted a prospective exploratory pilot study to identify the differences in esophageal protein profiles among PPI-responsive-EoE (PPI-R-EoE), PPI-nonresponsive-EoE (PPI-NR-EoE), and non-EoE controls using SOMAscan, a proteomics platform that allows simultaneous detection of 1305 human proteins.

The research team prospectively enrolled patients undergoing endoscopy for esophageal symptoms or for EoE follow-up, obtaining clinically indicated biopsies as well as extra samples from the midesophagus.

Patients who were diagnosed with EoE (at 15 or greater eosinophils per high-power field, or eos/hpf) were treated with 20 mg of omeprazole twice daily for 8 weeks, followed by repeat biopsies to assess treatment response.

Patients with histologic remission (fewer than 15 eos/hpf) were classified as PPI-R-EoE, whereas those with persistently active disease were classified as PPI-NR-EoE. Patients without EoE served as controls and were categorized as having erosive esophagitis (EE) or no esophagitis.

Overall, the study enrolled 32 patients, including 15 with PPI-R-EoE, eight with PPI-NR-EoE, three with EE, and six with no esophagitis. The demographics, symptoms, and endoscopic findings were similar between the PPI-R-EoE and PPI-NR-EoE patients.

At the index endoscopy, the PPI-R-EoE and PPI-NR-EoE patients had similar esophageal protein profiles, with only 20 proteins differentially expressed at a relaxed cutoff of P < .1. An analysis of the 20 proteins predicted lower expression of six proteins that may be associated with gastrointestinal inflammation in nonresponsive patients, including STAT1, STAT3, CFB, interleukin (IL)-17RA, TNFRSF1A, and SERPINA3.

In addition, 136 proteins — including 15 with corrected P < .05 — clearly discriminated PPI-R-EoE patients from non-EoE controls, and 255 proteins — including 249 with P < .05 — discriminated PPI-NR-EoE patients from controls. Both types of EoE patients had proteins associated with enhanced inflammation and vasculogenesis, as well as down-regulation of CRISP3 and DSG1 and upregulation of TNFAIP6.

The comparative analyses also showed that the follow-up biopsies of PPI-R-EoE patients had protein profiles that resembled non-EoE controls after PPI therapy.

“This further supports the hypothesis that despite the PPI response, PPI-R-EoE represents a subtype of EoE rather than gastroesophageal reflux disease (GERD),” Chan said.

 

Future EoE Considerations

Although most expressed proteins appeared similar between PPI-responsive and nonresponsive patients before treatment, a few proteins differed related to gastrointestinal inflammation, the study authors wrote, including some previously implicated in IL4 and IL13 inflammatory pathways.

“Further study of these proteins may provide insights into the EoE pathogenic pathway, explore their potential to predict PPI response at diagnosis, and identify possible therapeutic targets,” they wrote.

The authors pointed to the small study size as the primary limitation, noting that the pilot study was intended to explore the feasibility of using SomaScan to assess esophageal protein profiles in different EoE phenotypes. In the future, larger studies with more expansive candidate proteins could help characterize the differences and better identify specific proteins and pathways in EoE, they wrote.

“The takeaway is that PPI responsiveness does not distinguish EoE from GERD but rather PPI is a primary therapy for EoE independent of GERD,” said Marc Rothenberg, MD, director of allergy and immunology and director of the Cincinnati Center for Eosinophilic Disorders at Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio.

Rothenberg, who wasn’t involved with this study, has conducted transcriptome analyses of PPI-R-EoE, which showed PPI-reversible allergic inflammation.

“PPI-R-EoE and PPI-NR-EoE look the same at the molecular level,” he said. “After therapy, PPI-R-EoE normalizes, as per its definition.”

This study was supported by the Campaign Urging Research for Eosinophilic Disease Foundation Grant, the Kenneth and Louise Goldberg Junior Faculty Award, and a National Institutes of Health award. Chan declared advisory board positions with several pharmaceutical companies and Rothenberg reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — In patients with severe alcohol-associated hepatitis (SAH), tapering corticosteroids appears to be safer and as effective as a conventional fixed dose, according to new research.

“Although several drugs have been evaluated for severe alcohol-associated hepatitis, none have succeeded in practice. Corticosteroids remain the mainstay of treatment; however, infections remain a major concern in 25%-40% of cases,” said Anand Kulkarni, MD, senior consultant and director of critical care hepatology at the Asian Institute of Gastroenterology in Hyderabad, India.

“There are no standard society guidelines for steroid dosing, and our current practices stem from studies in the 1970s, so there’s a major knowledge gap around optimal dosing and if stepwise tapering helps,” said Kulkarni, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

 

Assessing Tapered Doses

In a multicenter, open-label randomized controlled trial, 254 patients with SAH from four Indian centers and one Canadian center were randomized to receive either a fixed or tapering dose of 40 mg prednisolone daily for 4 weeks. The patients in the tapering group received a starting dose of 40 mg, which was reduced by 10 mg weekly over 4 weeks.

While taking corticosteroids, 66% of those in the fixed dose group and 55% of those in the tapering group also received prophylactic antibiotics.

The mean age of participants was 41.1 years, the median Model For End-Stage Liver Disease score was 25.6, and 98.4% were men.

The primary objective was to compare the incidence of drug-related adverse events, infections, hospitalization, and mortality through day 90.

The duration of corticosteroid therapy was 22 days in the fixed dose group and 23 days in the tapering dose group.

Overall, the proportion of steroid responders was similar in both groups, at 80.3% in the fixed dose group and 82.5% in the tapering dose group.

However, the incidence of drug-related adverse events was significantly higher in the fixed dose group (52%) than in the tapering dose group (36.2%). The most common adverse events in both groups were infection, hyperglycemia, and hematochezia.

At 90 days, the incidence of infection was significantly lower in the tapering group (19.7%) than in the fixed dose group (33.1%). In both groups, the most common infection sites were the lungs (28.3%) and urinary tract (22.4%).

In terms of liver-related outcomes, some patients developed hepatic encephalopathy (11.8% in fixed dose vs 6.3% in tapering dose) and acute variceal bleed (3.1% in each group), as well as acute kidney injury (26.8% in fixed dose vs 18.9% in tapering dose).

Hospitalization within 90 days was required in 44.1% of the fixed dose group and 33.1% of the tapering dose group.

Survival at day 90 was 83.5% in the fixed dose group and 86.6% in the tapering dose group. Four patients in the fixed dose group and three patients in the tapering dose group underwent living donor liver transplantation by day 90.

Relapse of alcohol use by day 90 occurred in 13.4% of the fixed dose group and 12.6% of the tapering dose group.

“Rapid tapering in severe alcohol-associated hepatitis reduces infections and hospitalizations but doesn’t have a significant impact on survival,” Kulkarni concluded.

 

Considering Alternative Therapies

Given the high risk for infection in patients with SAH and limited certainty around benefits, the data may also call into question whether to give steroids to these patients at all, said session co-moderator Aleksander Krag, MD, professor of clinical medicine at the University of Southern Denmark, Odense, Denmark, and secretary general of the European Association for the Study of Liver 2023-2025.

“Since there are no other treatments available as of now, we’ll still continue to give steroids,” Kulkarni noted. But “tapering the dose should be beneficial.”

Although steroid therapy has been considered the “mainstay treatment” for SAH for 50 years, it doesn’t always lead to long-term improvement in liver values or survival, said Prasun Jalal, MD, the Stan and Sue Partee Endowed Chair in Hepatology at Baylor College of Medicine, Houston, who wasn’t involved with the study.

Researchers are looking to other connections, such as the gut microbiome, to find treatments for advanced alcoholic liver disease, Jalal said in an interview. In a small pilot study, he and colleagues found that intestinal microbiota transplantation (IMT) appears to be safe and effective for these patients.

“Early analyses suggest that IMT has a favorable outcome on the prognosis of patients with severe alcohol-associated hepatitis and is safe,” Jalal said. “A longer follow-up study with a larger sample size is in progress.”

Kulkarni and Krag reported no relevant disclosures. Jalal has speaking and teaching relationships with AbbVie and Madrigal.

A version of this article appeared on Medscape.com.

SAN DIEGO — In patients with severe alcohol-associated hepatitis (SAH), tapering corticosteroids appears to be safer and as effective as a conventional fixed dose, according to new research.

“Although several drugs have been evaluated for severe alcohol-associated hepatitis, none have succeeded in practice. Corticosteroids remain the mainstay of treatment; however, infections remain a major concern in 25%-40% of cases,” said Anand Kulkarni, MD, senior consultant and director of critical care hepatology at the Asian Institute of Gastroenterology in Hyderabad, India.

“There are no standard society guidelines for steroid dosing, and our current practices stem from studies in the 1970s, so there’s a major knowledge gap around optimal dosing and if stepwise tapering helps,” said Kulkarni, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

 

Assessing Tapered Doses

In a multicenter, open-label randomized controlled trial, 254 patients with SAH from four Indian centers and one Canadian center were randomized to receive either a fixed or tapering dose of 40 mg prednisolone daily for 4 weeks. The patients in the tapering group received a starting dose of 40 mg, which was reduced by 10 mg weekly over 4 weeks.

While taking corticosteroids, 66% of those in the fixed dose group and 55% of those in the tapering group also received prophylactic antibiotics.

The mean age of participants was 41.1 years, the median Model For End-Stage Liver Disease score was 25.6, and 98.4% were men.

The primary objective was to compare the incidence of drug-related adverse events, infections, hospitalization, and mortality through day 90.

The duration of corticosteroid therapy was 22 days in the fixed dose group and 23 days in the tapering dose group.

Overall, the proportion of steroid responders was similar in both groups, at 80.3% in the fixed dose group and 82.5% in the tapering dose group.

However, the incidence of drug-related adverse events was significantly higher in the fixed dose group (52%) than in the tapering dose group (36.2%). The most common adverse events in both groups were infection, hyperglycemia, and hematochezia.

At 90 days, the incidence of infection was significantly lower in the tapering group (19.7%) than in the fixed dose group (33.1%). In both groups, the most common infection sites were the lungs (28.3%) and urinary tract (22.4%).

In terms of liver-related outcomes, some patients developed hepatic encephalopathy (11.8% in fixed dose vs 6.3% in tapering dose) and acute variceal bleed (3.1% in each group), as well as acute kidney injury (26.8% in fixed dose vs 18.9% in tapering dose).

Hospitalization within 90 days was required in 44.1% of the fixed dose group and 33.1% of the tapering dose group.

Survival at day 90 was 83.5% in the fixed dose group and 86.6% in the tapering dose group. Four patients in the fixed dose group and three patients in the tapering dose group underwent living donor liver transplantation by day 90.

Relapse of alcohol use by day 90 occurred in 13.4% of the fixed dose group and 12.6% of the tapering dose group.

“Rapid tapering in severe alcohol-associated hepatitis reduces infections and hospitalizations but doesn’t have a significant impact on survival,” Kulkarni concluded.

 

Considering Alternative Therapies

Given the high risk for infection in patients with SAH and limited certainty around benefits, the data may also call into question whether to give steroids to these patients at all, said session co-moderator Aleksander Krag, MD, professor of clinical medicine at the University of Southern Denmark, Odense, Denmark, and secretary general of the European Association for the Study of Liver 2023-2025.

“Since there are no other treatments available as of now, we’ll still continue to give steroids,” Kulkarni noted. But “tapering the dose should be beneficial.”

Although steroid therapy has been considered the “mainstay treatment” for SAH for 50 years, it doesn’t always lead to long-term improvement in liver values or survival, said Prasun Jalal, MD, the Stan and Sue Partee Endowed Chair in Hepatology at Baylor College of Medicine, Houston, who wasn’t involved with the study.

Researchers are looking to other connections, such as the gut microbiome, to find treatments for advanced alcoholic liver disease, Jalal said in an interview. In a small pilot study, he and colleagues found that intestinal microbiota transplantation (IMT) appears to be safe and effective for these patients.

“Early analyses suggest that IMT has a favorable outcome on the prognosis of patients with severe alcohol-associated hepatitis and is safe,” Jalal said. “A longer follow-up study with a larger sample size is in progress.”

Kulkarni and Krag reported no relevant disclosures. Jalal has speaking and teaching relationships with AbbVie and Madrigal.

A version of this article appeared on Medscape.com.

SAN DIEGO — In patients with severe alcohol-associated hepatitis (SAH), tapering corticosteroids appears to be safer and as effective as a conventional fixed dose, according to new research.

“Although several drugs have been evaluated for severe alcohol-associated hepatitis, none have succeeded in practice. Corticosteroids remain the mainstay of treatment; however, infections remain a major concern in 25%-40% of cases,” said Anand Kulkarni, MD, senior consultant and director of critical care hepatology at the Asian Institute of Gastroenterology in Hyderabad, India.

“There are no standard society guidelines for steroid dosing, and our current practices stem from studies in the 1970s, so there’s a major knowledge gap around optimal dosing and if stepwise tapering helps,” said Kulkarni, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

 

Assessing Tapered Doses

In a multicenter, open-label randomized controlled trial, 254 patients with SAH from four Indian centers and one Canadian center were randomized to receive either a fixed or tapering dose of 40 mg prednisolone daily for 4 weeks. The patients in the tapering group received a starting dose of 40 mg, which was reduced by 10 mg weekly over 4 weeks.

While taking corticosteroids, 66% of those in the fixed dose group and 55% of those in the tapering group also received prophylactic antibiotics.

The mean age of participants was 41.1 years, the median Model For End-Stage Liver Disease score was 25.6, and 98.4% were men.

The primary objective was to compare the incidence of drug-related adverse events, infections, hospitalization, and mortality through day 90.

The duration of corticosteroid therapy was 22 days in the fixed dose group and 23 days in the tapering dose group.

Overall, the proportion of steroid responders was similar in both groups, at 80.3% in the fixed dose group and 82.5% in the tapering dose group.

However, the incidence of drug-related adverse events was significantly higher in the fixed dose group (52%) than in the tapering dose group (36.2%). The most common adverse events in both groups were infection, hyperglycemia, and hematochezia.

At 90 days, the incidence of infection was significantly lower in the tapering group (19.7%) than in the fixed dose group (33.1%). In both groups, the most common infection sites were the lungs (28.3%) and urinary tract (22.4%).

In terms of liver-related outcomes, some patients developed hepatic encephalopathy (11.8% in fixed dose vs 6.3% in tapering dose) and acute variceal bleed (3.1% in each group), as well as acute kidney injury (26.8% in fixed dose vs 18.9% in tapering dose).

Hospitalization within 90 days was required in 44.1% of the fixed dose group and 33.1% of the tapering dose group.

Survival at day 90 was 83.5% in the fixed dose group and 86.6% in the tapering dose group. Four patients in the fixed dose group and three patients in the tapering dose group underwent living donor liver transplantation by day 90.

Relapse of alcohol use by day 90 occurred in 13.4% of the fixed dose group and 12.6% of the tapering dose group.

“Rapid tapering in severe alcohol-associated hepatitis reduces infections and hospitalizations but doesn’t have a significant impact on survival,” Kulkarni concluded.

 

Considering Alternative Therapies

Given the high risk for infection in patients with SAH and limited certainty around benefits, the data may also call into question whether to give steroids to these patients at all, said session co-moderator Aleksander Krag, MD, professor of clinical medicine at the University of Southern Denmark, Odense, Denmark, and secretary general of the European Association for the Study of Liver 2023-2025.

“Since there are no other treatments available as of now, we’ll still continue to give steroids,” Kulkarni noted. But “tapering the dose should be beneficial.”

Although steroid therapy has been considered the “mainstay treatment” for SAH for 50 years, it doesn’t always lead to long-term improvement in liver values or survival, said Prasun Jalal, MD, the Stan and Sue Partee Endowed Chair in Hepatology at Baylor College of Medicine, Houston, who wasn’t involved with the study.

Researchers are looking to other connections, such as the gut microbiome, to find treatments for advanced alcoholic liver disease, Jalal said in an interview. In a small pilot study, he and colleagues found that intestinal microbiota transplantation (IMT) appears to be safe and effective for these patients.

“Early analyses suggest that IMT has a favorable outcome on the prognosis of patients with severe alcohol-associated hepatitis and is safe,” Jalal said. “A longer follow-up study with a larger sample size is in progress.”

Kulkarni and Krag reported no relevant disclosures. Jalal has speaking and teaching relationships with AbbVie and Madrigal.

A version of this article appeared on Medscape.com.

In children with asymptomatic potential celiac disease (PCD), a panel of seven serum proteomic biomarkers can predict which individuals will go on to develop villous atrophy (VA), according to investigators.

Given that PCD patients present with positive serology and intact duodenal architecture, these findings may provide a much-needed tool for identifying patients who are more likely to benefit from early dietary interventions, lead author Renata Auricchio, MD, PhD, of the University of Naples Federico II, Italy, and colleagues reported.

“PCD offers the unique opportunity to observe the progression of gluten-induced tissue damage in celiac disease,” the investigators wrote in Gastroenterology. “These patients recognize gluten and produce specific autoantibodies, but have not developed intestinal damage.”

The study included 31 children with asymptomatic PCD who were eating a gluten-containing diet. Serum samples from each child were analyzed for the relative abundance of 92 inflammation-linked proteins using a proximity extension immunoassay. Statistical analyses, including partial least squares discriminant and linear discriminant analyses, were then applied to identify which proteins were associated with the development of VA.

After a mean follow-up period of 5.85 years, 14 participants developed VA (ie, celiac disease), while the remaining 17 remained asymptomatic.

Panel analysis revealed that specific inflammatory proteins, including interleukin (IL)–20, IL-2, sirtuin 2 (SIRT2), leukemia inhibitory factor (LIF), IL-22 receptor subunit a1, cystatin D (CST5), IL-17 receptor A, IL-15 receptor subunit a (RA), CUB domain–containing protein 1 (CDCP1), and IL-14, were 1.23- to 1.76-fold higher in children who developed VA. Among these, seven proteins — CDCP1, IL-2, LIF, IL10RA, SIRT2, CST5, and IL-4 — were able to significantly distinguish between symptomatic and asymptomatic cases in a linear discriminant model. This panel of seven proteins achieved a predictive accuracy of 96.8% in identifying children at risk of VA.

Additionally, bioinformatics pathway analysis confirmed that the broader set of proteins is involved in the positive regulation of JAK-STAT signaling (involving IL-22 receptor subunit a1, IL-4, IL-20, IL10RA, LIF, and IL-2), inflammatory responses (IL-4, IL-20, LIF, and IL-2), and processes such as tyrosine phosphorylation, leukocyte differentiation, IgG isotype switching, and protein phosphorylation regulation. These findings suggest that gluten-induced inflammation may already be active in early stages of the disease, including the initial phases of leukocyte differentiation, according to the investigators.

“Over a long follow-up on a gluten-containing diet, only 40% of these patients progressed to VA,” Dr. Auricchio and colleagues wrote. “Notably, 25%-30% of children with PCD even stop producing anti–tissue transglutaminase antibodies, and the others keep on producing autoantibodies but preserve a normal intestinal mucosa. Considering these data, the decision to address a patient with PCD on a gluten-free diet at time of diagnosis is quite critical.”

The researchers noted that this new model, with accuracy exceeding 95%, is well suited for routine use because of its practicality and reliability.

“Our previous model, based mainly on small intestinal mucosa features, moved a step toward the prediction of outcome but still required a mucosal biopsy, and the accuracy of prediction was not greater than 80%, which is somewhat uncertain for a lifelong clinical decision,” they wrote. In contrast, the present model “appears to be sufficient to immediately suggest a gluten-free diet in children with PCD, who are almost certainly committed to developing VA.”

The investigators called for long-term studies to validate their findings in other cohorts, including adult populations.This study was supported by the TIMID project and Inflammation in Human Early Life: Targeting Impacts on Life Course Health (INITIALISE) by the Horizon Europe Program of the European Union. The investigators disclosed no conflicts of interest.

In children with asymptomatic potential celiac disease (PCD), a panel of seven serum proteomic biomarkers can predict which individuals will go on to develop villous atrophy (VA), according to investigators.

Given that PCD patients present with positive serology and intact duodenal architecture, these findings may provide a much-needed tool for identifying patients who are more likely to benefit from early dietary interventions, lead author Renata Auricchio, MD, PhD, of the University of Naples Federico II, Italy, and colleagues reported.

“PCD offers the unique opportunity to observe the progression of gluten-induced tissue damage in celiac disease,” the investigators wrote in Gastroenterology. “These patients recognize gluten and produce specific autoantibodies, but have not developed intestinal damage.”

The study included 31 children with asymptomatic PCD who were eating a gluten-containing diet. Serum samples from each child were analyzed for the relative abundance of 92 inflammation-linked proteins using a proximity extension immunoassay. Statistical analyses, including partial least squares discriminant and linear discriminant analyses, were then applied to identify which proteins were associated with the development of VA.

After a mean follow-up period of 5.85 years, 14 participants developed VA (ie, celiac disease), while the remaining 17 remained asymptomatic.

Panel analysis revealed that specific inflammatory proteins, including interleukin (IL)–20, IL-2, sirtuin 2 (SIRT2), leukemia inhibitory factor (LIF), IL-22 receptor subunit a1, cystatin D (CST5), IL-17 receptor A, IL-15 receptor subunit a (RA), CUB domain–containing protein 1 (CDCP1), and IL-14, were 1.23- to 1.76-fold higher in children who developed VA. Among these, seven proteins — CDCP1, IL-2, LIF, IL10RA, SIRT2, CST5, and IL-4 — were able to significantly distinguish between symptomatic and asymptomatic cases in a linear discriminant model. This panel of seven proteins achieved a predictive accuracy of 96.8% in identifying children at risk of VA.

Additionally, bioinformatics pathway analysis confirmed that the broader set of proteins is involved in the positive regulation of JAK-STAT signaling (involving IL-22 receptor subunit a1, IL-4, IL-20, IL10RA, LIF, and IL-2), inflammatory responses (IL-4, IL-20, LIF, and IL-2), and processes such as tyrosine phosphorylation, leukocyte differentiation, IgG isotype switching, and protein phosphorylation regulation. These findings suggest that gluten-induced inflammation may already be active in early stages of the disease, including the initial phases of leukocyte differentiation, according to the investigators.

“Over a long follow-up on a gluten-containing diet, only 40% of these patients progressed to VA,” Dr. Auricchio and colleagues wrote. “Notably, 25%-30% of children with PCD even stop producing anti–tissue transglutaminase antibodies, and the others keep on producing autoantibodies but preserve a normal intestinal mucosa. Considering these data, the decision to address a patient with PCD on a gluten-free diet at time of diagnosis is quite critical.”

The researchers noted that this new model, with accuracy exceeding 95%, is well suited for routine use because of its practicality and reliability.

“Our previous model, based mainly on small intestinal mucosa features, moved a step toward the prediction of outcome but still required a mucosal biopsy, and the accuracy of prediction was not greater than 80%, which is somewhat uncertain for a lifelong clinical decision,” they wrote. In contrast, the present model “appears to be sufficient to immediately suggest a gluten-free diet in children with PCD, who are almost certainly committed to developing VA.”

The investigators called for long-term studies to validate their findings in other cohorts, including adult populations.This study was supported by the TIMID project and Inflammation in Human Early Life: Targeting Impacts on Life Course Health (INITIALISE) by the Horizon Europe Program of the European Union. The investigators disclosed no conflicts of interest.

In children with asymptomatic potential celiac disease (PCD), a panel of seven serum proteomic biomarkers can predict which individuals will go on to develop villous atrophy (VA), according to investigators.

Given that PCD patients present with positive serology and intact duodenal architecture, these findings may provide a much-needed tool for identifying patients who are more likely to benefit from early dietary interventions, lead author Renata Auricchio, MD, PhD, of the University of Naples Federico II, Italy, and colleagues reported.

“PCD offers the unique opportunity to observe the progression of gluten-induced tissue damage in celiac disease,” the investigators wrote in Gastroenterology. “These patients recognize gluten and produce specific autoantibodies, but have not developed intestinal damage.”

The study included 31 children with asymptomatic PCD who were eating a gluten-containing diet. Serum samples from each child were analyzed for the relative abundance of 92 inflammation-linked proteins using a proximity extension immunoassay. Statistical analyses, including partial least squares discriminant and linear discriminant analyses, were then applied to identify which proteins were associated with the development of VA.

After a mean follow-up period of 5.85 years, 14 participants developed VA (ie, celiac disease), while the remaining 17 remained asymptomatic.

Panel analysis revealed that specific inflammatory proteins, including interleukin (IL)–20, IL-2, sirtuin 2 (SIRT2), leukemia inhibitory factor (LIF), IL-22 receptor subunit a1, cystatin D (CST5), IL-17 receptor A, IL-15 receptor subunit a (RA), CUB domain–containing protein 1 (CDCP1), and IL-14, were 1.23- to 1.76-fold higher in children who developed VA. Among these, seven proteins — CDCP1, IL-2, LIF, IL10RA, SIRT2, CST5, and IL-4 — were able to significantly distinguish between symptomatic and asymptomatic cases in a linear discriminant model. This panel of seven proteins achieved a predictive accuracy of 96.8% in identifying children at risk of VA.

Additionally, bioinformatics pathway analysis confirmed that the broader set of proteins is involved in the positive regulation of JAK-STAT signaling (involving IL-22 receptor subunit a1, IL-4, IL-20, IL10RA, LIF, and IL-2), inflammatory responses (IL-4, IL-20, LIF, and IL-2), and processes such as tyrosine phosphorylation, leukocyte differentiation, IgG isotype switching, and protein phosphorylation regulation. These findings suggest that gluten-induced inflammation may already be active in early stages of the disease, including the initial phases of leukocyte differentiation, according to the investigators.

“Over a long follow-up on a gluten-containing diet, only 40% of these patients progressed to VA,” Dr. Auricchio and colleagues wrote. “Notably, 25%-30% of children with PCD even stop producing anti–tissue transglutaminase antibodies, and the others keep on producing autoantibodies but preserve a normal intestinal mucosa. Considering these data, the decision to address a patient with PCD on a gluten-free diet at time of diagnosis is quite critical.”

The researchers noted that this new model, with accuracy exceeding 95%, is well suited for routine use because of its practicality and reliability.

“Our previous model, based mainly on small intestinal mucosa features, moved a step toward the prediction of outcome but still required a mucosal biopsy, and the accuracy of prediction was not greater than 80%, which is somewhat uncertain for a lifelong clinical decision,” they wrote. In contrast, the present model “appears to be sufficient to immediately suggest a gluten-free diet in children with PCD, who are almost certainly committed to developing VA.”

The investigators called for long-term studies to validate their findings in other cohorts, including adult populations.This study was supported by the TIMID project and Inflammation in Human Early Life: Targeting Impacts on Life Course Health (INITIALISE) by the Horizon Europe Program of the European Union. The investigators disclosed no conflicts of interest.