Carolyn Crist

Clinicians generally shouldn’t use potassium-competitive acid blockers (P-CAB) as first-line therapy for acid-related conditions, nonerosive gastroesophageal reflux disease (GERD), or peptic ulcer disease, according to a recent clinical practice update from the American Gastroenterological Association (AGA).

However, P-CABs are recommended in place of proton pump inhibitors (PPIs) for most patients with Helicobacter pylori and other conditions where patients haven’t responded to PPIs.

“P-CABs are a newer medication class now available in the US, associated with more rapid, potent, and prolonged gastric acid inhibition than PPI formulations,” said lead author Amit Patel, MD, a gastroenterologist at the Duke University School of Medicine and Durham Veterans Affairs Medical Center, Durham, North Carolina.

 

“P-CABs have potentially significant clinical benefits in the management of Helicobacter pylori infection and GERD, particularly more severe erosive esophagitis,” he said. “Emerging data are affording additional insights into the clinical benefits of P-CABs in settings such as on-demand therapy for reflux-associated symptoms, bleeding gastroduodenal ulcers, and endoscopic eradication therapy for Barrett’s esophagus.”

The update was published in Gastroenterology .

 

P-CAB Developments

For most patients, PPIs and histamine-2 receptor antagonists remain the primary way to inhibit gastric acid secretion for common upper gastrointestinal conditions, the authors wrote. However, P-CABs such as vonoprazan and tegoprazan may provide relief when PPIs have limitations.

Unlike PPIs, P-CABs are considered acid-stable, don’t require premeal dosing, aren’t prodrugs, and don’t require conversion to an active form to provide pharmacologic effects. They tend to have longer half-lives and more rapid onset. Serum gastrin levels typically remain higher with P-CABs.

In terms of safety, randomized trial data indicate that P-CABs are generally well tolerated and have short-term and medium-term safety similar to PPIs. Due to potent acid suppression, enteric infection risks remain higher, though long-term safety data is needed, the authors wrote.

Overall, P-CABs appear to be equally as potent or more potent than PPIs, though more potent acid inhibition isn’t necessarily associated with better outcomes, the authors wrote. For most foregut acid-related disorders — such as heartburn and prevention of nonsteroidal anti-inflammatory drug–associated ulcers — P-CABs can help when patients fail PPI therapy.

In general, though, nonclinical factors related to cost, barriers to obtaining medication, and limited long-term safety data may outweigh the advantages of P-CABs, especially if clinical superiority isn’t yet known, the authors wrote. 

For GERD, clinicians generally shouldn’t use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. However, P-CABs should be used for those with documented acid-related reflux who fail therapy with twice-daily PPIs. They may also be appropriate for on-demand heartburn therapy, although more evidence is needed.

For erosive esophagitis, P-CABs generally shouldn’t be used for milder cases but can be considered for patients with more severe cases that haven’t responded to PPIs, including refractory esophagitis.

For H pylori, P-CABs should be used in place of PPIs for eradication regimens, including among patients with clarithromycin-resistant strains. In contrast with most of the other indications in the update, the short-term duration of H pylori treatment reduced the authors’ concerns about P-CAB costs and safety.

For peptic ulcer disease, P-CABs generally shouldn’t be used as first-line treatment or prophylaxis. However, the rapid onset and potent acid inhibition could be useful for patients with bleeding gastroduodenal ulcers and high-risk stigmata.

“Emerging data will allow refinements in the populations and clinical settings for which P-CABs at various doses may be considered and advised — and may reveal more clinical scenarios in which they can provide meaningful benefit,” Patel said. “Further investigations, including additional populations and novel indicators, as well as evaluating long-term safety data and cost-effectiveness, are warranted, as P-CABs are incorporated more broadly into clinical practice worldwide.”
 
The authors received no specific funding for this update. Patel reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Clinicians generally shouldn’t use potassium-competitive acid blockers (P-CAB) as first-line therapy for acid-related conditions, nonerosive gastroesophageal reflux disease (GERD), or peptic ulcer disease, according to a recent clinical practice update from the American Gastroenterological Association (AGA).

However, P-CABs are recommended in place of proton pump inhibitors (PPIs) for most patients with Helicobacter pylori and other conditions where patients haven’t responded to PPIs.

“P-CABs are a newer medication class now available in the US, associated with more rapid, potent, and prolonged gastric acid inhibition than PPI formulations,” said lead author Amit Patel, MD, a gastroenterologist at the Duke University School of Medicine and Durham Veterans Affairs Medical Center, Durham, North Carolina.

 

“P-CABs have potentially significant clinical benefits in the management of Helicobacter pylori infection and GERD, particularly more severe erosive esophagitis,” he said. “Emerging data are affording additional insights into the clinical benefits of P-CABs in settings such as on-demand therapy for reflux-associated symptoms, bleeding gastroduodenal ulcers, and endoscopic eradication therapy for Barrett’s esophagus.”

The update was published in Gastroenterology .

 

P-CAB Developments

For most patients, PPIs and histamine-2 receptor antagonists remain the primary way to inhibit gastric acid secretion for common upper gastrointestinal conditions, the authors wrote. However, P-CABs such as vonoprazan and tegoprazan may provide relief when PPIs have limitations.

Unlike PPIs, P-CABs are considered acid-stable, don’t require premeal dosing, aren’t prodrugs, and don’t require conversion to an active form to provide pharmacologic effects. They tend to have longer half-lives and more rapid onset. Serum gastrin levels typically remain higher with P-CABs.

In terms of safety, randomized trial data indicate that P-CABs are generally well tolerated and have short-term and medium-term safety similar to PPIs. Due to potent acid suppression, enteric infection risks remain higher, though long-term safety data is needed, the authors wrote.

Overall, P-CABs appear to be equally as potent or more potent than PPIs, though more potent acid inhibition isn’t necessarily associated with better outcomes, the authors wrote. For most foregut acid-related disorders — such as heartburn and prevention of nonsteroidal anti-inflammatory drug–associated ulcers — P-CABs can help when patients fail PPI therapy.

In general, though, nonclinical factors related to cost, barriers to obtaining medication, and limited long-term safety data may outweigh the advantages of P-CABs, especially if clinical superiority isn’t yet known, the authors wrote. 

For GERD, clinicians generally shouldn’t use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. However, P-CABs should be used for those with documented acid-related reflux who fail therapy with twice-daily PPIs. They may also be appropriate for on-demand heartburn therapy, although more evidence is needed.

For erosive esophagitis, P-CABs generally shouldn’t be used for milder cases but can be considered for patients with more severe cases that haven’t responded to PPIs, including refractory esophagitis.

For H pylori, P-CABs should be used in place of PPIs for eradication regimens, including among patients with clarithromycin-resistant strains. In contrast with most of the other indications in the update, the short-term duration of H pylori treatment reduced the authors’ concerns about P-CAB costs and safety.

For peptic ulcer disease, P-CABs generally shouldn’t be used as first-line treatment or prophylaxis. However, the rapid onset and potent acid inhibition could be useful for patients with bleeding gastroduodenal ulcers and high-risk stigmata.

“Emerging data will allow refinements in the populations and clinical settings for which P-CABs at various doses may be considered and advised — and may reveal more clinical scenarios in which they can provide meaningful benefit,” Patel said. “Further investigations, including additional populations and novel indicators, as well as evaluating long-term safety data and cost-effectiveness, are warranted, as P-CABs are incorporated more broadly into clinical practice worldwide.”
 
The authors received no specific funding for this update. Patel reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Clinicians generally shouldn’t use potassium-competitive acid blockers (P-CAB) as first-line therapy for acid-related conditions, nonerosive gastroesophageal reflux disease (GERD), or peptic ulcer disease, according to a recent clinical practice update from the American Gastroenterological Association (AGA).

However, P-CABs are recommended in place of proton pump inhibitors (PPIs) for most patients with Helicobacter pylori and other conditions where patients haven’t responded to PPIs.

“P-CABs are a newer medication class now available in the US, associated with more rapid, potent, and prolonged gastric acid inhibition than PPI formulations,” said lead author Amit Patel, MD, a gastroenterologist at the Duke University School of Medicine and Durham Veterans Affairs Medical Center, Durham, North Carolina.

 

“P-CABs have potentially significant clinical benefits in the management of Helicobacter pylori infection and GERD, particularly more severe erosive esophagitis,” he said. “Emerging data are affording additional insights into the clinical benefits of P-CABs in settings such as on-demand therapy for reflux-associated symptoms, bleeding gastroduodenal ulcers, and endoscopic eradication therapy for Barrett’s esophagus.”

The update was published in Gastroenterology .

 

P-CAB Developments

For most patients, PPIs and histamine-2 receptor antagonists remain the primary way to inhibit gastric acid secretion for common upper gastrointestinal conditions, the authors wrote. However, P-CABs such as vonoprazan and tegoprazan may provide relief when PPIs have limitations.

Unlike PPIs, P-CABs are considered acid-stable, don’t require premeal dosing, aren’t prodrugs, and don’t require conversion to an active form to provide pharmacologic effects. They tend to have longer half-lives and more rapid onset. Serum gastrin levels typically remain higher with P-CABs.

In terms of safety, randomized trial data indicate that P-CABs are generally well tolerated and have short-term and medium-term safety similar to PPIs. Due to potent acid suppression, enteric infection risks remain higher, though long-term safety data is needed, the authors wrote.

Overall, P-CABs appear to be equally as potent or more potent than PPIs, though more potent acid inhibition isn’t necessarily associated with better outcomes, the authors wrote. For most foregut acid-related disorders — such as heartburn and prevention of nonsteroidal anti-inflammatory drug–associated ulcers — P-CABs can help when patients fail PPI therapy.

In general, though, nonclinical factors related to cost, barriers to obtaining medication, and limited long-term safety data may outweigh the advantages of P-CABs, especially if clinical superiority isn’t yet known, the authors wrote. 

For GERD, clinicians generally shouldn’t use P-CABs as first-line therapy for patients with uninvestigated heartburn symptoms or nonerosive reflux disease. However, P-CABs should be used for those with documented acid-related reflux who fail therapy with twice-daily PPIs. They may also be appropriate for on-demand heartburn therapy, although more evidence is needed.

For erosive esophagitis, P-CABs generally shouldn’t be used for milder cases but can be considered for patients with more severe cases that haven’t responded to PPIs, including refractory esophagitis.

For H pylori, P-CABs should be used in place of PPIs for eradication regimens, including among patients with clarithromycin-resistant strains. In contrast with most of the other indications in the update, the short-term duration of H pylori treatment reduced the authors’ concerns about P-CAB costs and safety.

For peptic ulcer disease, P-CABs generally shouldn’t be used as first-line treatment or prophylaxis. However, the rapid onset and potent acid inhibition could be useful for patients with bleeding gastroduodenal ulcers and high-risk stigmata.

“Emerging data will allow refinements in the populations and clinical settings for which P-CABs at various doses may be considered and advised — and may reveal more clinical scenarios in which they can provide meaningful benefit,” Patel said. “Further investigations, including additional populations and novel indicators, as well as evaluating long-term safety data and cost-effectiveness, are warranted, as P-CABs are incorporated more broadly into clinical practice worldwide.”
 
The authors received no specific funding for this update. Patel 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.

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.

SAN DIEGO — An artificial intelligence (AI)–driven algorithm may be able to accurately detect early-stage metabolic dysfunction–associated steatotic liver disease (MASLD) based on imaging findings and other criteria in patient electronic medical records, according to new research.

Among the patients identified by the algorithm as meeting the criteria for MASLD, only a small percentage had an MASLD-associated diagnostic code.

“A significant portion of patients who meet criteria for MASLD go undiagnosed, which can lead to delays in care and progression to advanced liver disease,” said lead author Ariana Stuart, MD, an internal medicine resident at the University of Washington, Seattle, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“However, people shouldn’t interpret our findings as a lack of primary care training or management,” she said. “Instead, this study indicates that AI can complement physician workflow and address the limitations of traditional clinical practice.”

 

Developing an MASLD Algorithm

Typically, the identification of MASLD has relied on clinician recognition and descriptions in chart notes, Stuart said. Early-stage disease often goes unnoticed, particularly if patients remain asymptomatic, until cirrhosis develops.

To address this, Stuart and colleagues created a machine learning, natural language processing AI algorithm on the basis of MASLD criteria from AASLD: Hepatic steatosis on imaging and at least one metabolic factor (elevated body mass index, hypertension, prediabetes or diabetes, or dyslipidemia). The model was validated by two physicians, who manually reviewed monthly cohorts generated by the algorithm.

Between December 2023 and May 2024, the researchers used the algorithm to analyze an MASLD cohort from medical centers in the Seattle area. The mean age was 51 years, 44% were women, and 68% were White. Those with alcohol-associated liver disease, metastatic malignancy, and autoimmune, genetic, and infectious causes of liver disease were excluded.

The algorithm identified 957 patients with imaging that matched MASLD criteria.

Among those, 137 patients (17%) identified by the algorithm had an MASLD-associated diagnostic code. For these patients, the mean time from initial imaging with steatosis to diagnosis was 33 days, according to patient records.

An additional 26 patients received an MASLD diagnosis during the study period, with a mean time to diagnosis of 56.2 days.

In terms of patient management, 245 patients (26%) had contact with a gastroenterologist or hepatologist based on documentation of a letter, phone call, or office visit. In addition, 546 patients (57%) were screened for hepatitis C.

After adjusting for an over-inclusion error rate of 12.8% and an overdiagnosis rate of 0.02%, the research team found 697 patients (83%) lacked a relevant diagnosis. After multiple iterations, the algorithm achieved an accuracy of about 88%, Stuart said.

 

Considering Future AI Use

Stuart and colleagues are now testing the algorithm in larger groups and across longer periods.

After that, they intend to implement a quality improvement program to increase awareness for clinicians and primary care providers, as well as train users on how to interpret and move forward with findings of hepatic steatosis in patient records.

For instance, future AI models could flag patients for additional testing, improve chart review, and aid in research efforts around cardiometabolic comorbidities associated with MASLD, she said.

Looking ahead, AI tools such as these represent what’s possible for advancements in research, patient care, and clinical workflows, said Ashley Spann, MD, assistant professor and transplant hepatologist at Vanderbilt University, Nashville, Tennessee, and director of clinical research informatics for Vanderbilt’s Gastroenterology Division.

“AI, in my view, is actually augmented intelligence,” she added. “We need to think about the people and processes involved.”

Spann, who spoke about the use of AI tools in medicine in general, stressed the need for transparency in AI use, careful validation of input-output data, frameworks for machine learning models in medicine, and standardization across institutions.

“What we ultimately need is an infrastructure that supports the simultaneous deployment and evaluation of these models,” she said. “We all need to be on the same page and make sure our models work in multiple settings and make adjustments based on algorithmovigilance afterward.”

Stuart reported no relevant disclosures. Spann serves on Epic’s hepatology steering board, which has focused on how to use AI tools in electronic medical records.

A version of this article appeared on Medscape.com.

SAN DIEGO — An artificial intelligence (AI)–driven algorithm may be able to accurately detect early-stage metabolic dysfunction–associated steatotic liver disease (MASLD) based on imaging findings and other criteria in patient electronic medical records, according to new research.

Among the patients identified by the algorithm as meeting the criteria for MASLD, only a small percentage had an MASLD-associated diagnostic code.

“A significant portion of patients who meet criteria for MASLD go undiagnosed, which can lead to delays in care and progression to advanced liver disease,” said lead author Ariana Stuart, MD, an internal medicine resident at the University of Washington, Seattle, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“However, people shouldn’t interpret our findings as a lack of primary care training or management,” she said. “Instead, this study indicates that AI can complement physician workflow and address the limitations of traditional clinical practice.”

 

Developing an MASLD Algorithm

Typically, the identification of MASLD has relied on clinician recognition and descriptions in chart notes, Stuart said. Early-stage disease often goes unnoticed, particularly if patients remain asymptomatic, until cirrhosis develops.

To address this, Stuart and colleagues created a machine learning, natural language processing AI algorithm on the basis of MASLD criteria from AASLD: Hepatic steatosis on imaging and at least one metabolic factor (elevated body mass index, hypertension, prediabetes or diabetes, or dyslipidemia). The model was validated by two physicians, who manually reviewed monthly cohorts generated by the algorithm.

Between December 2023 and May 2024, the researchers used the algorithm to analyze an MASLD cohort from medical centers in the Seattle area. The mean age was 51 years, 44% were women, and 68% were White. Those with alcohol-associated liver disease, metastatic malignancy, and autoimmune, genetic, and infectious causes of liver disease were excluded.

The algorithm identified 957 patients with imaging that matched MASLD criteria.

Among those, 137 patients (17%) identified by the algorithm had an MASLD-associated diagnostic code. For these patients, the mean time from initial imaging with steatosis to diagnosis was 33 days, according to patient records.

An additional 26 patients received an MASLD diagnosis during the study period, with a mean time to diagnosis of 56.2 days.

In terms of patient management, 245 patients (26%) had contact with a gastroenterologist or hepatologist based on documentation of a letter, phone call, or office visit. In addition, 546 patients (57%) were screened for hepatitis C.

After adjusting for an over-inclusion error rate of 12.8% and an overdiagnosis rate of 0.02%, the research team found 697 patients (83%) lacked a relevant diagnosis. After multiple iterations, the algorithm achieved an accuracy of about 88%, Stuart said.

 

Considering Future AI Use

Stuart and colleagues are now testing the algorithm in larger groups and across longer periods.

After that, they intend to implement a quality improvement program to increase awareness for clinicians and primary care providers, as well as train users on how to interpret and move forward with findings of hepatic steatosis in patient records.

For instance, future AI models could flag patients for additional testing, improve chart review, and aid in research efforts around cardiometabolic comorbidities associated with MASLD, she said.

Looking ahead, AI tools such as these represent what’s possible for advancements in research, patient care, and clinical workflows, said Ashley Spann, MD, assistant professor and transplant hepatologist at Vanderbilt University, Nashville, Tennessee, and director of clinical research informatics for Vanderbilt’s Gastroenterology Division.

“AI, in my view, is actually augmented intelligence,” she added. “We need to think about the people and processes involved.”

Spann, who spoke about the use of AI tools in medicine in general, stressed the need for transparency in AI use, careful validation of input-output data, frameworks for machine learning models in medicine, and standardization across institutions.

“What we ultimately need is an infrastructure that supports the simultaneous deployment and evaluation of these models,” she said. “We all need to be on the same page and make sure our models work in multiple settings and make adjustments based on algorithmovigilance afterward.”

Stuart reported no relevant disclosures. Spann serves on Epic’s hepatology steering board, which has focused on how to use AI tools in electronic medical records.

A version of this article appeared on Medscape.com.

SAN DIEGO — An artificial intelligence (AI)–driven algorithm may be able to accurately detect early-stage metabolic dysfunction–associated steatotic liver disease (MASLD) based on imaging findings and other criteria in patient electronic medical records, according to new research.

Among the patients identified by the algorithm as meeting the criteria for MASLD, only a small percentage had an MASLD-associated diagnostic code.

“A significant portion of patients who meet criteria for MASLD go undiagnosed, which can lead to delays in care and progression to advanced liver disease,” said lead author Ariana Stuart, MD, an internal medicine resident at the University of Washington, Seattle, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

“However, people shouldn’t interpret our findings as a lack of primary care training or management,” she said. “Instead, this study indicates that AI can complement physician workflow and address the limitations of traditional clinical practice.”

 

Developing an MASLD Algorithm

Typically, the identification of MASLD has relied on clinician recognition and descriptions in chart notes, Stuart said. Early-stage disease often goes unnoticed, particularly if patients remain asymptomatic, until cirrhosis develops.

To address this, Stuart and colleagues created a machine learning, natural language processing AI algorithm on the basis of MASLD criteria from AASLD: Hepatic steatosis on imaging and at least one metabolic factor (elevated body mass index, hypertension, prediabetes or diabetes, or dyslipidemia). The model was validated by two physicians, who manually reviewed monthly cohorts generated by the algorithm.

Between December 2023 and May 2024, the researchers used the algorithm to analyze an MASLD cohort from medical centers in the Seattle area. The mean age was 51 years, 44% were women, and 68% were White. Those with alcohol-associated liver disease, metastatic malignancy, and autoimmune, genetic, and infectious causes of liver disease were excluded.

The algorithm identified 957 patients with imaging that matched MASLD criteria.

Among those, 137 patients (17%) identified by the algorithm had an MASLD-associated diagnostic code. For these patients, the mean time from initial imaging with steatosis to diagnosis was 33 days, according to patient records.

An additional 26 patients received an MASLD diagnosis during the study period, with a mean time to diagnosis of 56.2 days.

In terms of patient management, 245 patients (26%) had contact with a gastroenterologist or hepatologist based on documentation of a letter, phone call, or office visit. In addition, 546 patients (57%) were screened for hepatitis C.

After adjusting for an over-inclusion error rate of 12.8% and an overdiagnosis rate of 0.02%, the research team found 697 patients (83%) lacked a relevant diagnosis. After multiple iterations, the algorithm achieved an accuracy of about 88%, Stuart said.

 

Considering Future AI Use

Stuart and colleagues are now testing the algorithm in larger groups and across longer periods.

After that, they intend to implement a quality improvement program to increase awareness for clinicians and primary care providers, as well as train users on how to interpret and move forward with findings of hepatic steatosis in patient records.

For instance, future AI models could flag patients for additional testing, improve chart review, and aid in research efforts around cardiometabolic comorbidities associated with MASLD, she said.

Looking ahead, AI tools such as these represent what’s possible for advancements in research, patient care, and clinical workflows, said Ashley Spann, MD, assistant professor and transplant hepatologist at Vanderbilt University, Nashville, Tennessee, and director of clinical research informatics for Vanderbilt’s Gastroenterology Division.

“AI, in my view, is actually augmented intelligence,” she added. “We need to think about the people and processes involved.”

Spann, who spoke about the use of AI tools in medicine in general, stressed the need for transparency in AI use, careful validation of input-output data, frameworks for machine learning models in medicine, and standardization across institutions.

“What we ultimately need is an infrastructure that supports the simultaneous deployment and evaluation of these models,” she said. “We all need to be on the same page and make sure our models work in multiple settings and make adjustments based on algorithmovigilance afterward.”

Stuart reported no relevant disclosures. Spann serves on Epic’s hepatology steering board, which has focused on how to use AI tools in electronic medical records.

A version of this article appeared on Medscape.com.

SAN DIEGO — Semaglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, appears to safely and effectively treat metabolic dysfunction–associated steatohepatitis (MASH) among patients with moderate to advanced liver fibrosis, according to interim results from a phase 3 trial.

At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.

“It’s been a long journey. I’ve been working with GLP-1s for 16 years, and it’s great to be able to report the first GLP-1 receptor agonist to demonstrate efficacy in a phase 3 trial for MASH,” said lead author Philip Newsome, MD, PhD, director of the Roger Williams Institute of Liver Studies at King’s College London in England.

“There were also improvements in a slew of other noninvasive markers,” said Newsome, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

Although already seen in a broader context, “it’s nice to see a demonstration of the cardiometabolic benefits in the context of MASH and a reassuring safety profile,” he added.

 

Interim ESSENCE Trial Analysis

ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.

The trial includes 1200 participants with biopsy-defined MASH and fibrosis, stages F2 and F3, who were randomized 2:1 to a once-weekly subcutaneous injection of 2.4 mg of semaglutide or placebo for 240 weeks. After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.

In a planned interim analysis, the trial investigators evaluated the primary endpoints at week 72 for the first 800 participants, with biopsies taken at weeks 1 and 72.

A total of 534 people were randomized to the semaglutide group, including 169 with F2 fibrosis and 365 with F3 fibrosis. Among the 266 participants randomized to placebo, 81 had F2 fibrosis and 185 had F3 fibrosis.

At baseline, the patient characteristics were similar between the groups (mean age, 56 years; body mass index, 34.6). A majority of participants also were White (67.5%), women (57.1%), had type 2 diabetes (55.9%), F3 fibrosis (68.8%), and enhanced liver fibrosis (ELF) scores around 10 (55.5%).

For the first primary endpoint, 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. This represented an estimated difference in responder proportions (EDP) of 28.9%.

In addition, 37% of those in the semaglutide group and 22.5% of those in the placebo group met the second primary endpoint of improvement in liver fibrosis with no worsening of steatohepatitis (EDP, 14.4%).

Among the secondary endpoints, combined resolution of steatohepatitis with a one-stage improvement in liver fibrosis occurred in 32.8% of the semaglutide group and 16.2% of the placebo group (EDP, 16.6%).

In additional analyses, Newsome and colleagues found 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.

Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group.

Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.

Although not considered statistically significant, patients in the semaglutide group also reported greater reductions in body pain.

In a safety analysis of 1195 participants at 96 weeks, adverse events, severe adverse events, and discontinuations were similar in both groups. Not surprisingly, gastrointestinal side effects were more commonly reported in the semaglutide group, Newsome said.

 

Highly Anticipated Results

After Newsome’s presentation, attendees applauded.

Rohit Loomba, MD, a gastroenterologist at the University of California, San Diego, who was not involved with the study, called the results the “highlight of the meeting.”

This sentiment was echoed by Naga Chalasani, MD, AGAF, a gastroenterologist at Indiana University Medical Center, Indianapolis, who called the results a “watershed moment in the MASH field” with “terrific data.”

 

Based on questions after the presentation, Newsome indicated that future ESSENCE reports would look at certain aspects of the results, such as the 10% weight loss among those in the semaglutide group, as well as the mechanisms of histological and fibrosis improvement.

“We know from other GLP-1 trials that more weight loss occurs in those who don’t have type 2 diabetes, and we’re still running those analyses,” he said. “Weight loss is clearly a major contributor to MASH improvement, but there seem to be some weight-independent effects here, which are likely linked to insulin sensitivity or inflammation. We look forward to presenting those analyses in due course.”

 

In a comment, Kimberly Ann Brown, MD, AGAF, chief of gastroenterology and hepatology at Henry Ford Health System in Detroit, Michigan, AASLD Foundation chair, and comoderator of the late-breaking abstract session, spoke about the highly anticipated presentation.

“This study was really the pinnacle of this meeting. We’ve all been waiting for this data, in large part because many of our patients are already using these medications,” Brown said. “Seeing the benefit for the liver, as well as lipids and other cardiovascular measures, is so important. Having this confirmatory study will hopefully lead to the availability of the medication for this indication among our patients.”

Newsome reported numerous disclosures, including consultant relationships with pharmaceutical companies, such as Novo Nordisk, Boehringer Ingelheim, and Madrigal Pharmaceuticals. Loomba has research grant relationships with numerous companies, including Hanmi, Gilead, Galmed Pharmaceuticals, Galectin Therapeutics, Eli Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. Chalasani has consultant relationships with Ipsen, Pfizer, Merck, Altimmune, GSK, Madrigal Pharmaceuticals, and Zydus. Brown reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Semaglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, appears to safely and effectively treat metabolic dysfunction–associated steatohepatitis (MASH) among patients with moderate to advanced liver fibrosis, according to interim results from a phase 3 trial.

At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.

“It’s been a long journey. I’ve been working with GLP-1s for 16 years, and it’s great to be able to report the first GLP-1 receptor agonist to demonstrate efficacy in a phase 3 trial for MASH,” said lead author Philip Newsome, MD, PhD, director of the Roger Williams Institute of Liver Studies at King’s College London in England.

“There were also improvements in a slew of other noninvasive markers,” said Newsome, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

Although already seen in a broader context, “it’s nice to see a demonstration of the cardiometabolic benefits in the context of MASH and a reassuring safety profile,” he added.

 

Interim ESSENCE Trial Analysis

ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.

The trial includes 1200 participants with biopsy-defined MASH and fibrosis, stages F2 and F3, who were randomized 2:1 to a once-weekly subcutaneous injection of 2.4 mg of semaglutide or placebo for 240 weeks. After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.

In a planned interim analysis, the trial investigators evaluated the primary endpoints at week 72 for the first 800 participants, with biopsies taken at weeks 1 and 72.

A total of 534 people were randomized to the semaglutide group, including 169 with F2 fibrosis and 365 with F3 fibrosis. Among the 266 participants randomized to placebo, 81 had F2 fibrosis and 185 had F3 fibrosis.

At baseline, the patient characteristics were similar between the groups (mean age, 56 years; body mass index, 34.6). A majority of participants also were White (67.5%), women (57.1%), had type 2 diabetes (55.9%), F3 fibrosis (68.8%), and enhanced liver fibrosis (ELF) scores around 10 (55.5%).

For the first primary endpoint, 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. This represented an estimated difference in responder proportions (EDP) of 28.9%.

In addition, 37% of those in the semaglutide group and 22.5% of those in the placebo group met the second primary endpoint of improvement in liver fibrosis with no worsening of steatohepatitis (EDP, 14.4%).

Among the secondary endpoints, combined resolution of steatohepatitis with a one-stage improvement in liver fibrosis occurred in 32.8% of the semaglutide group and 16.2% of the placebo group (EDP, 16.6%).

In additional analyses, Newsome and colleagues found 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.

Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group.

Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.

Although not considered statistically significant, patients in the semaglutide group also reported greater reductions in body pain.

In a safety analysis of 1195 participants at 96 weeks, adverse events, severe adverse events, and discontinuations were similar in both groups. Not surprisingly, gastrointestinal side effects were more commonly reported in the semaglutide group, Newsome said.

 

Highly Anticipated Results

After Newsome’s presentation, attendees applauded.

Rohit Loomba, MD, a gastroenterologist at the University of California, San Diego, who was not involved with the study, called the results the “highlight of the meeting.”

This sentiment was echoed by Naga Chalasani, MD, AGAF, a gastroenterologist at Indiana University Medical Center, Indianapolis, who called the results a “watershed moment in the MASH field” with “terrific data.”

 

Based on questions after the presentation, Newsome indicated that future ESSENCE reports would look at certain aspects of the results, such as the 10% weight loss among those in the semaglutide group, as well as the mechanisms of histological and fibrosis improvement.

“We know from other GLP-1 trials that more weight loss occurs in those who don’t have type 2 diabetes, and we’re still running those analyses,” he said. “Weight loss is clearly a major contributor to MASH improvement, but there seem to be some weight-independent effects here, which are likely linked to insulin sensitivity or inflammation. We look forward to presenting those analyses in due course.”

 

In a comment, Kimberly Ann Brown, MD, AGAF, chief of gastroenterology and hepatology at Henry Ford Health System in Detroit, Michigan, AASLD Foundation chair, and comoderator of the late-breaking abstract session, spoke about the highly anticipated presentation.

“This study was really the pinnacle of this meeting. We’ve all been waiting for this data, in large part because many of our patients are already using these medications,” Brown said. “Seeing the benefit for the liver, as well as lipids and other cardiovascular measures, is so important. Having this confirmatory study will hopefully lead to the availability of the medication for this indication among our patients.”

Newsome reported numerous disclosures, including consultant relationships with pharmaceutical companies, such as Novo Nordisk, Boehringer Ingelheim, and Madrigal Pharmaceuticals. Loomba has research grant relationships with numerous companies, including Hanmi, Gilead, Galmed Pharmaceuticals, Galectin Therapeutics, Eli Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. Chalasani has consultant relationships with Ipsen, Pfizer, Merck, Altimmune, GSK, Madrigal Pharmaceuticals, and Zydus. Brown reported no relevant disclosures.

A version of this article appeared on Medscape.com.

SAN DIEGO — Semaglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, appears to safely and effectively treat metabolic dysfunction–associated steatohepatitis (MASH) among patients with moderate to advanced liver fibrosis, according to interim results from a phase 3 trial.

At 72 weeks, a 2.4-mg once-weekly subcutaneous dose of semaglutide demonstrated superiority, compared with placebo, for the two primary endpoints: Resolution of steatohepatitis with no worsening of fibrosis and improvement in liver fibrosis with no worsening of steatohepatitis.

“It’s been a long journey. I’ve been working with GLP-1s for 16 years, and it’s great to be able to report the first GLP-1 receptor agonist to demonstrate efficacy in a phase 3 trial for MASH,” said lead author Philip Newsome, MD, PhD, director of the Roger Williams Institute of Liver Studies at King’s College London in England.

“There were also improvements in a slew of other noninvasive markers,” said Newsome, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

Although already seen in a broader context, “it’s nice to see a demonstration of the cardiometabolic benefits in the context of MASH and a reassuring safety profile,” he added.

 

Interim ESSENCE Trial Analysis

ESSENCE (NCT04822181) is an ongoing multicenter, phase 3 randomized, double-blind, placebo-controlled outcome trial studying semaglutide for the potential treatment of MASH.

The trial includes 1200 participants with biopsy-defined MASH and fibrosis, stages F2 and F3, who were randomized 2:1 to a once-weekly subcutaneous injection of 2.4 mg of semaglutide or placebo for 240 weeks. After initiation, the semaglutide dosage was increased every 4 weeks up to 16 weeks when the full dose (2.4 mg) was reached.

In a planned interim analysis, the trial investigators evaluated the primary endpoints at week 72 for the first 800 participants, with biopsies taken at weeks 1 and 72.

A total of 534 people were randomized to the semaglutide group, including 169 with F2 fibrosis and 365 with F3 fibrosis. Among the 266 participants randomized to placebo, 81 had F2 fibrosis and 185 had F3 fibrosis.

At baseline, the patient characteristics were similar between the groups (mean age, 56 years; body mass index, 34.6). A majority of participants also were White (67.5%), women (57.1%), had type 2 diabetes (55.9%), F3 fibrosis (68.8%), and enhanced liver fibrosis (ELF) scores around 10 (55.5%).

For the first primary endpoint, 62.9% of those in the semaglutide group and 34.1% of those in the placebo group reached resolution of steatohepatitis with no worsening of fibrosis. This represented an estimated difference in responder proportions (EDP) of 28.9%.

In addition, 37% of those in the semaglutide group and 22.5% of those in the placebo group met the second primary endpoint of improvement in liver fibrosis with no worsening of steatohepatitis (EDP, 14.4%).

Among the secondary endpoints, combined resolution of steatohepatitis with a one-stage improvement in liver fibrosis occurred in 32.8% of the semaglutide group and 16.2% of the placebo group (EDP, 16.6%).

In additional analyses, Newsome and colleagues found 20%-40% improvements in liver enzymes and noninvasive fibrosis markers, such as ELF and vibration-controlled transient elastography liver stiffness.

Weight loss was also significant, with a 10.5% reduction in the semaglutide group compared with a 2% reduction in the placebo group.

Cardiometabolic risk factors improved as well, with changes in blood pressure measurements, hemoglobin A1c scores, and cholesterol values.

Although not considered statistically significant, patients in the semaglutide group also reported greater reductions in body pain.

In a safety analysis of 1195 participants at 96 weeks, adverse events, severe adverse events, and discontinuations were similar in both groups. Not surprisingly, gastrointestinal side effects were more commonly reported in the semaglutide group, Newsome said.

 

Highly Anticipated Results

After Newsome’s presentation, attendees applauded.

Rohit Loomba, MD, a gastroenterologist at the University of California, San Diego, who was not involved with the study, called the results the “highlight of the meeting.”

This sentiment was echoed by Naga Chalasani, MD, AGAF, a gastroenterologist at Indiana University Medical Center, Indianapolis, who called the results a “watershed moment in the MASH field” with “terrific data.”

 

Based on questions after the presentation, Newsome indicated that future ESSENCE reports would look at certain aspects of the results, such as the 10% weight loss among those in the semaglutide group, as well as the mechanisms of histological and fibrosis improvement.

“We know from other GLP-1 trials that more weight loss occurs in those who don’t have type 2 diabetes, and we’re still running those analyses,” he said. “Weight loss is clearly a major contributor to MASH improvement, but there seem to be some weight-independent effects here, which are likely linked to insulin sensitivity or inflammation. We look forward to presenting those analyses in due course.”

 

In a comment, Kimberly Ann Brown, MD, AGAF, chief of gastroenterology and hepatology at Henry Ford Health System in Detroit, Michigan, AASLD Foundation chair, and comoderator of the late-breaking abstract session, spoke about the highly anticipated presentation.

“This study was really the pinnacle of this meeting. We’ve all been waiting for this data, in large part because many of our patients are already using these medications,” Brown said. “Seeing the benefit for the liver, as well as lipids and other cardiovascular measures, is so important. Having this confirmatory study will hopefully lead to the availability of the medication for this indication among our patients.”

Newsome reported numerous disclosures, including consultant relationships with pharmaceutical companies, such as Novo Nordisk, Boehringer Ingelheim, and Madrigal Pharmaceuticals. Loomba has research grant relationships with numerous companies, including Hanmi, Gilead, Galmed Pharmaceuticals, Galectin Therapeutics, Eli Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. Chalasani has consultant relationships with Ipsen, Pfizer, Merck, Altimmune, GSK, Madrigal Pharmaceuticals, and Zydus. Brown reported no relevant disclosures.

A version of this article appeared on Medscape.com.