Liver Disease

SAN DIEGO – The presence of five key proteins in the blood was strongly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) as much as 16 years before symptoms appeared, new research showed.

“This represents the first high-performance, ultra-early (16 years) predictive model for MASLD,” said first author Shiyi Yu, MD, resident physician in the department of gastroenterology, Guangdong Provincial People’s Hospital in China.

“The findings could be a game-changer for how we screen for and intervene in liver disease,” Yu said at a press briefing for Digestive Disease Week® (DDW) 2025.

“Instead of waiting for symptoms or irreversible damage, we can [identify] high-risk individuals early and take steps to prevent MASLD from developing, which is particularly important because MASLD often progresses silently until advanced stages,” she added.

MASLD is the most common liver disorder in the world and carries a high risk of morbidity and mortality, with a mortality rate that is doubled compared with those without MASLD.

To identify any long-term predictive markers that could be used in simple predictive models, Yu and colleagues evaluated data on 52,952 participants enrolled in the UK Biobank between 2006 and 2010 who did not have MASLD at baseline and were followed up for up to 16.6 years.

Overall, 782 participants were diagnosed with MASLD over the course of the study.

A total of 2,737 blood proteins were analyzed, and among them, the five that emerged as being robust predictive biomarkers for development of MASLD within 5 years included CDHR2 (area under the curve [AUC] = 0.825), FUOM (AUC = 0.815), KRT18 (AUC = 0.810), ACY1 (AUC = 0.803), and GGT1 (AUC = 0.797). 

Deviations of the proteins in plasma concentrations were observed up to 16 years prior to MASLD onset, with higher levels of the proteins at baseline associated with up to a nearly 10-times higher risk of MASLD (hazard ratios, 7.05-9.81). 

A combination of the five proteins was predictive of incident MASLD at all time frames, including at 5-years (AUC = 0.857), 10-years (AUC = 0.775), and at all time points (AUC = 0.758).

The combined proteins gained even stronger predictive performance when added to key clinical biomarkers such as BMI and daily exercise, with an accuracy of 90.4% at 5 years and 82.2% at 16 years, “surpassing all existing short-term prediction models,” Yu reported.

Similar results were observed with the predictive model in a separate, smaller cohort of 100 participants in China, “further supporting the robustness of the model and showing it can be effective across diverse populations,” she noted in the press briefing.

 

Potential for Interventions ‘Years Before’ Damage Begins

Yu underscored the potential benefits of informing patients of their risk of MASLD.

“Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms,” she said.

A protein-based risk score could “profoundly transform early intervention strategies, triggering personalized lifestyle interventions for high-risk individuals” she said. 

With obesity, type 2 diabetes, and high cholesterol levels among key risk factors for MASLD, such personalized interventions could include “counseling on diet, physical activity, and other factors years before liver damage begins, potentially averting disease progression altogether,” Yu noted.

Instead of waiting for abnormal liver function tests or imaging findings, patients could receive more frequent monitoring with annual elastography or ultrasound, for example, she explained.

In addition, “knowing one’s individualized protein-based risk may be more effective than abstract measures such as BMI or liver enzymes in motivating patients, facilitating better patient engagement and adherence,” Yu said.While noting that more work is needed to understand the biology behind the biomarkers, Yu underscored that “this is a big step toward personalized prevention.”

“By finding at-risk patients early, we hope to help stop MASLD before it starts,” she concluded.

 

Predictive Performance Impressive

Commenting on the study at the press briefing, Loren A. Laine, MD, AGAF, professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Conn., and council chair of DDW 2025, noted that — as far as AUCs go — even a ranking in the 80% range is considered good. “So, for this to have an accuracy up to the 90s indicates a really excellent [predictive] performance,” he explained.

Laine agreed that the study findings have “the potential value to identify individuals at increased risk,” allowing for early monitoring and interventions. 

The interventions “could be either general, such as things like diet and lifestyle, or more specific,” based on the function of these proteins, he added.

Rotonya Carr, MD, the division head of gastroenterology at the University of Washington, Seattle, further highlighted the pressing need for better predictive tools in MASLD.

“The predictions are that if we don’t do anything, as many as 122 million people will be impacted by MASLD” in the US by 2050, she told GI & Hepatology News. 

“So, I am very excited about this work because we really don’t have anything right now that predicts who is going to get MASLD,” she said. “We are going to need tools like this, where people have information about their future health in order to make decisions.”

MASLD is known to be a significant risk factor for cardiovascular disease (CVD), and Carr speculated that the findings could lead to the types of predictive tools already available for CVD.

“I see this as being akin to what cardiology has had for quite some time, where they have cardiovascular risk disease calculators in which patients or their physicians can enter data and then estimate their risk of developing cardiovascular disease over, for instance, 10 years,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer. Carr’s disclosures include relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO – The presence of five key proteins in the blood was strongly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) as much as 16 years before symptoms appeared, new research showed.

“This represents the first high-performance, ultra-early (16 years) predictive model for MASLD,” said first author Shiyi Yu, MD, resident physician in the department of gastroenterology, Guangdong Provincial People’s Hospital in China.

“The findings could be a game-changer for how we screen for and intervene in liver disease,” Yu said at a press briefing for Digestive Disease Week® (DDW) 2025.

“Instead of waiting for symptoms or irreversible damage, we can [identify] high-risk individuals early and take steps to prevent MASLD from developing, which is particularly important because MASLD often progresses silently until advanced stages,” she added.

MASLD is the most common liver disorder in the world and carries a high risk of morbidity and mortality, with a mortality rate that is doubled compared with those without MASLD.

To identify any long-term predictive markers that could be used in simple predictive models, Yu and colleagues evaluated data on 52,952 participants enrolled in the UK Biobank between 2006 and 2010 who did not have MASLD at baseline and were followed up for up to 16.6 years.

Overall, 782 participants were diagnosed with MASLD over the course of the study.

A total of 2,737 blood proteins were analyzed, and among them, the five that emerged as being robust predictive biomarkers for development of MASLD within 5 years included CDHR2 (area under the curve [AUC] = 0.825), FUOM (AUC = 0.815), KRT18 (AUC = 0.810), ACY1 (AUC = 0.803), and GGT1 (AUC = 0.797). 

Deviations of the proteins in plasma concentrations were observed up to 16 years prior to MASLD onset, with higher levels of the proteins at baseline associated with up to a nearly 10-times higher risk of MASLD (hazard ratios, 7.05-9.81). 

A combination of the five proteins was predictive of incident MASLD at all time frames, including at 5-years (AUC = 0.857), 10-years (AUC = 0.775), and at all time points (AUC = 0.758).

The combined proteins gained even stronger predictive performance when added to key clinical biomarkers such as BMI and daily exercise, with an accuracy of 90.4% at 5 years and 82.2% at 16 years, “surpassing all existing short-term prediction models,” Yu reported.

Similar results were observed with the predictive model in a separate, smaller cohort of 100 participants in China, “further supporting the robustness of the model and showing it can be effective across diverse populations,” she noted in the press briefing.

 

Potential for Interventions ‘Years Before’ Damage Begins

Yu underscored the potential benefits of informing patients of their risk of MASLD.

“Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms,” she said.

A protein-based risk score could “profoundly transform early intervention strategies, triggering personalized lifestyle interventions for high-risk individuals” she said. 

With obesity, type 2 diabetes, and high cholesterol levels among key risk factors for MASLD, such personalized interventions could include “counseling on diet, physical activity, and other factors years before liver damage begins, potentially averting disease progression altogether,” Yu noted.

Instead of waiting for abnormal liver function tests or imaging findings, patients could receive more frequent monitoring with annual elastography or ultrasound, for example, she explained.

In addition, “knowing one’s individualized protein-based risk may be more effective than abstract measures such as BMI or liver enzymes in motivating patients, facilitating better patient engagement and adherence,” Yu said.While noting that more work is needed to understand the biology behind the biomarkers, Yu underscored that “this is a big step toward personalized prevention.”

“By finding at-risk patients early, we hope to help stop MASLD before it starts,” she concluded.

 

Predictive Performance Impressive

Commenting on the study at the press briefing, Loren A. Laine, MD, AGAF, professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Conn., and council chair of DDW 2025, noted that — as far as AUCs go — even a ranking in the 80% range is considered good. “So, for this to have an accuracy up to the 90s indicates a really excellent [predictive] performance,” he explained.

Laine agreed that the study findings have “the potential value to identify individuals at increased risk,” allowing for early monitoring and interventions. 

The interventions “could be either general, such as things like diet and lifestyle, or more specific,” based on the function of these proteins, he added.

Rotonya Carr, MD, the division head of gastroenterology at the University of Washington, Seattle, further highlighted the pressing need for better predictive tools in MASLD.

“The predictions are that if we don’t do anything, as many as 122 million people will be impacted by MASLD” in the US by 2050, she told GI & Hepatology News. 

“So, I am very excited about this work because we really don’t have anything right now that predicts who is going to get MASLD,” she said. “We are going to need tools like this, where people have information about their future health in order to make decisions.”

MASLD is known to be a significant risk factor for cardiovascular disease (CVD), and Carr speculated that the findings could lead to the types of predictive tools already available for CVD.

“I see this as being akin to what cardiology has had for quite some time, where they have cardiovascular risk disease calculators in which patients or their physicians can enter data and then estimate their risk of developing cardiovascular disease over, for instance, 10 years,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer. Carr’s disclosures include relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

SAN DIEGO – The presence of five key proteins in the blood was strongly associated with the development of metabolic dysfunction-associated steatotic liver disease (MASLD) as much as 16 years before symptoms appeared, new research showed.

“This represents the first high-performance, ultra-early (16 years) predictive model for MASLD,” said first author Shiyi Yu, MD, resident physician in the department of gastroenterology, Guangdong Provincial People’s Hospital in China.

“The findings could be a game-changer for how we screen for and intervene in liver disease,” Yu said at a press briefing for Digestive Disease Week® (DDW) 2025.

“Instead of waiting for symptoms or irreversible damage, we can [identify] high-risk individuals early and take steps to prevent MASLD from developing, which is particularly important because MASLD often progresses silently until advanced stages,” she added.

MASLD is the most common liver disorder in the world and carries a high risk of morbidity and mortality, with a mortality rate that is doubled compared with those without MASLD.

To identify any long-term predictive markers that could be used in simple predictive models, Yu and colleagues evaluated data on 52,952 participants enrolled in the UK Biobank between 2006 and 2010 who did not have MASLD at baseline and were followed up for up to 16.6 years.

Overall, 782 participants were diagnosed with MASLD over the course of the study.

A total of 2,737 blood proteins were analyzed, and among them, the five that emerged as being robust predictive biomarkers for development of MASLD within 5 years included CDHR2 (area under the curve [AUC] = 0.825), FUOM (AUC = 0.815), KRT18 (AUC = 0.810), ACY1 (AUC = 0.803), and GGT1 (AUC = 0.797). 

Deviations of the proteins in plasma concentrations were observed up to 16 years prior to MASLD onset, with higher levels of the proteins at baseline associated with up to a nearly 10-times higher risk of MASLD (hazard ratios, 7.05-9.81). 

A combination of the five proteins was predictive of incident MASLD at all time frames, including at 5-years (AUC = 0.857), 10-years (AUC = 0.775), and at all time points (AUC = 0.758).

The combined proteins gained even stronger predictive performance when added to key clinical biomarkers such as BMI and daily exercise, with an accuracy of 90.4% at 5 years and 82.2% at 16 years, “surpassing all existing short-term prediction models,” Yu reported.

Similar results were observed with the predictive model in a separate, smaller cohort of 100 participants in China, “further supporting the robustness of the model and showing it can be effective across diverse populations,” she noted in the press briefing.

 

Potential for Interventions ‘Years Before’ Damage Begins

Yu underscored the potential benefits of informing patients of their risk of MASLD.

“Too often, people do not find out they are at risk for liver disease before they are diagnosed and coping with symptoms,” she said.

A protein-based risk score could “profoundly transform early intervention strategies, triggering personalized lifestyle interventions for high-risk individuals” she said. 

With obesity, type 2 diabetes, and high cholesterol levels among key risk factors for MASLD, such personalized interventions could include “counseling on diet, physical activity, and other factors years before liver damage begins, potentially averting disease progression altogether,” Yu noted.

Instead of waiting for abnormal liver function tests or imaging findings, patients could receive more frequent monitoring with annual elastography or ultrasound, for example, she explained.

In addition, “knowing one’s individualized protein-based risk may be more effective than abstract measures such as BMI or liver enzymes in motivating patients, facilitating better patient engagement and adherence,” Yu said.While noting that more work is needed to understand the biology behind the biomarkers, Yu underscored that “this is a big step toward personalized prevention.”

“By finding at-risk patients early, we hope to help stop MASLD before it starts,” she concluded.

 

Predictive Performance Impressive

Commenting on the study at the press briefing, Loren A. Laine, MD, AGAF, professor of medicine and chief of the Section of Digestive Diseases at the Yale School of Medicine, New Haven, Conn., and council chair of DDW 2025, noted that — as far as AUCs go — even a ranking in the 80% range is considered good. “So, for this to have an accuracy up to the 90s indicates a really excellent [predictive] performance,” he explained.

Laine agreed that the study findings have “the potential value to identify individuals at increased risk,” allowing for early monitoring and interventions. 

The interventions “could be either general, such as things like diet and lifestyle, or more specific,” based on the function of these proteins, he added.

Rotonya Carr, MD, the division head of gastroenterology at the University of Washington, Seattle, further highlighted the pressing need for better predictive tools in MASLD.

“The predictions are that if we don’t do anything, as many as 122 million people will be impacted by MASLD” in the US by 2050, she told GI & Hepatology News. 

“So, I am very excited about this work because we really don’t have anything right now that predicts who is going to get MASLD,” she said. “We are going to need tools like this, where people have information about their future health in order to make decisions.”

MASLD is known to be a significant risk factor for cardiovascular disease (CVD), and Carr speculated that the findings could lead to the types of predictive tools already available for CVD.

“I see this as being akin to what cardiology has had for quite some time, where they have cardiovascular risk disease calculators in which patients or their physicians can enter data and then estimate their risk of developing cardiovascular disease over, for instance, 10 years,” she said.

Laine’s disclosures include consulting and/or relationships with Medtronic, Phathom Pharmaceuticals, Biohaven, Celgene, Intercept, Merck, and Pfizer. Carr’s disclosures include relationships with Intercept and Novo Nordisk and research funding from Merck.

A version of this article appeared on Medscape.com.

WASHINGTON — When a published case of auto-brewery syndrome (ABS) in China — caused by Klebsiella pneumoniae — received widespread publicity in 2019, patients reacted, sending emails to lead author Jing Yuan, in Beijing, China. Many of these inquiries were from patients in the United States who believed they might have ABS.

“Can you check to see if I have ABS?” patients asked Yuan.

For help, Yuan contacted Bernd Schnabl, MD, AGAF, at the University of California, San Diego, whose research was addressing alcohol-associated liver disease and who was also interested in the gut-liver axis and the role of gut microbiome–derived ethanol in metabolic dysfunction–associated steatotic liver disease (MASLD).

“She asked me, ‘Are you interested in looking into ABS?” Schnabl recalled at the Gut Microbiota for Health (GMFH) World Summit 2025. He dug in and formed what may be the largest research cohort thus far of patients with ABS — a group of 22 patients with their diagnosis confirmed through observed glucose challenge.

His soon-to-be-published research on this cohort has confirmed excess ethanol production — and elevations of both proteobacteria and fermentation pathways — in patients whose ABS symptoms had flared.

ABS is considered a rare condition, but “I’d argue that it’s rarely diagnosed because many physicians don’t know of the diagnosis, and many are actually very skeptical about the disease,” Schnabl said at the meeting, convened by AGA and the European Society of Neurogastroenterology and Motility.

Patients experience symptoms of intoxication when ethanol produced by dysregulated gut microbiota exceeds the capacity of the liver to metabolize it and accumulates in the blood, he explained.

“Patients constantly talk about brain fog; they can’t concentrate, and it can be very severe,” he said. “They don’t get a firm diagnosis and go from one medical center to another, and they also suffer from complications of alcohol use disorder including serious family, social, and legal problems.”

 

Advancing Knowledge, Findings From the Cohort

The phenomenon of ethanol production by gut microbiota has been known for over a century, Schnabl wrote with two co-authors in a 2024 review in Nature Reviews Gastroenterology & Hepatology of “endogenous ethanol production in health and disease.”

And in recent decades, he said at the meeting, research has linked endogenous ethanol production to MASLD, positioning it as a potential contributor to disease pathogenesis. In one of the most recently published studies, patients with MASLD had higher concentrations of ethanol in their systemic circulation after a mixed meal test than did healthy controls — and even higher ethanol concentrations in their portal vein blood, “suggesting that this ethanol is coming from the gut microbiome,” Schnabl said.

The paper from China that led Schnabl to establish his cohort was spurred on by a patient with both ABS and MASLD cirrhosis. The patient was found to have strains of high alcohol–producing K pneumoniae in the gut microbiome. When the researchers transplanted these strains into mice via fecal microbiota transplantation (FMT), the mice developed MASLD.

Schnabl’s study focused just on ABS, which is alternatively sometimes called gut fermentation syndrome. The 22 patients in his ABS cohort — each of whom provided stool samples corresponding to remission or flare of ABS symptoms — had a median age of 45 years and were predominantly men, slightly overweight and not obese, and without liver disease. (About 48 patients with suspected ABS were screened, and 20 were excluded after an observed glucose challenge failed to establish a diagnosis; 6 withdrew from the study.)

During remission (no symptoms), patients’ mean blood alcohol content (BAC) level was zero, but during a flare, the mean BAC level was 136 mg/dL. “To put it into perspective, the legal limit for driving in the US is 80 mg/dL,” Schnabl said. Within a mean of 4 hours after the oral glucose load used for diagnosis, patients’ mean BAC level was 73 mg/dL, he noted.

To assess ethanol production by the patients’ microbiota, Schnabl and his team cultured the stool samples — anaerobically adding glucose and measuring ethanol production — and compared the results with findings from stool samples collected from household partners who generally were of the opposite sex. Among their findings: cultures of stool from patients experiencing a flare produced significantly more ethanol than stool from household partners and samples from patients in remission.

To assess whether ethanol was produced by bacteria or fungi, the researchers measured ethanol production in cultures treated with either the antifungal amphotericin B or the antibiotic chloramphenicol. “Chloramphenicol clearly decreased the ethanol production,” Schnabl said. “So at least in this culture test, bacteria produced most of the alcohol in our patients.”

Taxonomic profiling, moreover, revealed “significantly elevated levels” of proteobacteria — with relative abundance of Escherichia coli and K pneumoniae — in patients who were flaring, he said. And functional profiling of the fecal microbiota showed much higher activity of fermentation pathways during patients’ flares than in household partners or healthy controls. (Healthy controls were incorporated into the taxonomic and functional profiling parts of the research.)

 

A Clinical Approach to ABS

Schnabl said at the meeting that stool cultures of both household partners and patients in long-term remission “all produced some low amount of ethanol, which was initially puzzling to us” but became less surprising as he and his colleagues reviewed more of the literature.

Asked during a discussion period whether ABS could explain chronic fatigue, a commonly reported chronic symptom in populations, Schnabl said it’s possible. And in an interview after the meeting, he elaborated. “The literature clearly says ABS is a rare disease, but I argue that more patients may have ABS; they just don’t know it. And I suspect some may have mild symptoms, like brain fog, feeling tired,” he said. “But at this point, this is complete speculation.”

Physicians should “be aware that if a patient has unexplained symptoms that could be aligned with ABS, checking the blood alcohol level” may be warranted, he said in the interview. A PEth (phosphatidylethanol) test — a biomarker test used to check for longer-term alcohol consumption — is an option, but it is important to appreciate it will not discriminate between exogenous alcohol drinking and endogenous ethanol production.

There are no standardized diagnostic tests for ABS, but at the meeting, Schnabl outlined a clinical approach, starting with a standardized oral glucose tolerance challenge test to detect elevated ethanol concentrations.

A fecal yeast test is warranted for diagnosed patients on the basis of some case reports in which ABS symptoms have improved with antifungal treatments. When the fecal yeast test is negative, “ideally you want to identify the ethanol-producing intestinal bacteria in the patient,” he said, using cultures and fecal metagenomics sequencing.

Treatment could then be tailored to the identified microbial strain, with options being selective antibiotics, probiotics and/or prebiotics, and — likely in the future — phages or FMT, he said. (These options, all aimed at restoring gut homeostasis, are also discussed in his 2024 review.)

Schnabl and his team recently performed FMT in a patient with ABS in whom E coli was determined to be producing excessive ethanol. The FMT, performed after antibiotic pretreatment, resulted in decreases in the relative abundance of proteobacteria and E coli levels, lower blood alcohol levels and fermentation enrichment pathways, and normalized liver enzymes.

After 6 months, however, the patient relapsed, and the measurements reversed. “We decided to do FMT every month, and we treated the patient for 6 months,” Schnabl said, noting that ABS had rendered the patient dysfunctional and unable to work. “He has been out of treatment for over a year now and is not flaring any longer.”

Schnabl and Elizabeth Hohmann, MD, at Massachusetts General Hospital, Boston, are currently recruiting patients with confirmed ABS for a National Institutes of Health–funded phase 1 safety and tolerability study of FMT for ABS.

Schnabl disclosed serving as an external scientific advisor/consultant to Ambys Medicines, Boehringer Ingelheim, Gelesis, Mabwell Therapeutics, Surrozen, and Takeda; and as the founder/BOD/BEO of Nterica Bio.

A version of this article appeared on Medscape.com.

WASHINGTON — When a published case of auto-brewery syndrome (ABS) in China — caused by Klebsiella pneumoniae — received widespread publicity in 2019, patients reacted, sending emails to lead author Jing Yuan, in Beijing, China. Many of these inquiries were from patients in the United States who believed they might have ABS.

“Can you check to see if I have ABS?” patients asked Yuan.

For help, Yuan contacted Bernd Schnabl, MD, AGAF, at the University of California, San Diego, whose research was addressing alcohol-associated liver disease and who was also interested in the gut-liver axis and the role of gut microbiome–derived ethanol in metabolic dysfunction–associated steatotic liver disease (MASLD).

“She asked me, ‘Are you interested in looking into ABS?” Schnabl recalled at the Gut Microbiota for Health (GMFH) World Summit 2025. He dug in and formed what may be the largest research cohort thus far of patients with ABS — a group of 22 patients with their diagnosis confirmed through observed glucose challenge.

His soon-to-be-published research on this cohort has confirmed excess ethanol production — and elevations of both proteobacteria and fermentation pathways — in patients whose ABS symptoms had flared.

ABS is considered a rare condition, but “I’d argue that it’s rarely diagnosed because many physicians don’t know of the diagnosis, and many are actually very skeptical about the disease,” Schnabl said at the meeting, convened by AGA and the European Society of Neurogastroenterology and Motility.

Patients experience symptoms of intoxication when ethanol produced by dysregulated gut microbiota exceeds the capacity of the liver to metabolize it and accumulates in the blood, he explained.

“Patients constantly talk about brain fog; they can’t concentrate, and it can be very severe,” he said. “They don’t get a firm diagnosis and go from one medical center to another, and they also suffer from complications of alcohol use disorder including serious family, social, and legal problems.”

 

Advancing Knowledge, Findings From the Cohort

The phenomenon of ethanol production by gut microbiota has been known for over a century, Schnabl wrote with two co-authors in a 2024 review in Nature Reviews Gastroenterology & Hepatology of “endogenous ethanol production in health and disease.”

And in recent decades, he said at the meeting, research has linked endogenous ethanol production to MASLD, positioning it as a potential contributor to disease pathogenesis. In one of the most recently published studies, patients with MASLD had higher concentrations of ethanol in their systemic circulation after a mixed meal test than did healthy controls — and even higher ethanol concentrations in their portal vein blood, “suggesting that this ethanol is coming from the gut microbiome,” Schnabl said.

The paper from China that led Schnabl to establish his cohort was spurred on by a patient with both ABS and MASLD cirrhosis. The patient was found to have strains of high alcohol–producing K pneumoniae in the gut microbiome. When the researchers transplanted these strains into mice via fecal microbiota transplantation (FMT), the mice developed MASLD.

Schnabl’s study focused just on ABS, which is alternatively sometimes called gut fermentation syndrome. The 22 patients in his ABS cohort — each of whom provided stool samples corresponding to remission or flare of ABS symptoms — had a median age of 45 years and were predominantly men, slightly overweight and not obese, and without liver disease. (About 48 patients with suspected ABS were screened, and 20 were excluded after an observed glucose challenge failed to establish a diagnosis; 6 withdrew from the study.)

During remission (no symptoms), patients’ mean blood alcohol content (BAC) level was zero, but during a flare, the mean BAC level was 136 mg/dL. “To put it into perspective, the legal limit for driving in the US is 80 mg/dL,” Schnabl said. Within a mean of 4 hours after the oral glucose load used for diagnosis, patients’ mean BAC level was 73 mg/dL, he noted.

To assess ethanol production by the patients’ microbiota, Schnabl and his team cultured the stool samples — anaerobically adding glucose and measuring ethanol production — and compared the results with findings from stool samples collected from household partners who generally were of the opposite sex. Among their findings: cultures of stool from patients experiencing a flare produced significantly more ethanol than stool from household partners and samples from patients in remission.

To assess whether ethanol was produced by bacteria or fungi, the researchers measured ethanol production in cultures treated with either the antifungal amphotericin B or the antibiotic chloramphenicol. “Chloramphenicol clearly decreased the ethanol production,” Schnabl said. “So at least in this culture test, bacteria produced most of the alcohol in our patients.”

Taxonomic profiling, moreover, revealed “significantly elevated levels” of proteobacteria — with relative abundance of Escherichia coli and K pneumoniae — in patients who were flaring, he said. And functional profiling of the fecal microbiota showed much higher activity of fermentation pathways during patients’ flares than in household partners or healthy controls. (Healthy controls were incorporated into the taxonomic and functional profiling parts of the research.)

 

A Clinical Approach to ABS

Schnabl said at the meeting that stool cultures of both household partners and patients in long-term remission “all produced some low amount of ethanol, which was initially puzzling to us” but became less surprising as he and his colleagues reviewed more of the literature.

Asked during a discussion period whether ABS could explain chronic fatigue, a commonly reported chronic symptom in populations, Schnabl said it’s possible. And in an interview after the meeting, he elaborated. “The literature clearly says ABS is a rare disease, but I argue that more patients may have ABS; they just don’t know it. And I suspect some may have mild symptoms, like brain fog, feeling tired,” he said. “But at this point, this is complete speculation.”

Physicians should “be aware that if a patient has unexplained symptoms that could be aligned with ABS, checking the blood alcohol level” may be warranted, he said in the interview. A PEth (phosphatidylethanol) test — a biomarker test used to check for longer-term alcohol consumption — is an option, but it is important to appreciate it will not discriminate between exogenous alcohol drinking and endogenous ethanol production.

There are no standardized diagnostic tests for ABS, but at the meeting, Schnabl outlined a clinical approach, starting with a standardized oral glucose tolerance challenge test to detect elevated ethanol concentrations.

A fecal yeast test is warranted for diagnosed patients on the basis of some case reports in which ABS symptoms have improved with antifungal treatments. When the fecal yeast test is negative, “ideally you want to identify the ethanol-producing intestinal bacteria in the patient,” he said, using cultures and fecal metagenomics sequencing.

Treatment could then be tailored to the identified microbial strain, with options being selective antibiotics, probiotics and/or prebiotics, and — likely in the future — phages or FMT, he said. (These options, all aimed at restoring gut homeostasis, are also discussed in his 2024 review.)

Schnabl and his team recently performed FMT in a patient with ABS in whom E coli was determined to be producing excessive ethanol. The FMT, performed after antibiotic pretreatment, resulted in decreases in the relative abundance of proteobacteria and E coli levels, lower blood alcohol levels and fermentation enrichment pathways, and normalized liver enzymes.

After 6 months, however, the patient relapsed, and the measurements reversed. “We decided to do FMT every month, and we treated the patient for 6 months,” Schnabl said, noting that ABS had rendered the patient dysfunctional and unable to work. “He has been out of treatment for over a year now and is not flaring any longer.”

Schnabl and Elizabeth Hohmann, MD, at Massachusetts General Hospital, Boston, are currently recruiting patients with confirmed ABS for a National Institutes of Health–funded phase 1 safety and tolerability study of FMT for ABS.

Schnabl disclosed serving as an external scientific advisor/consultant to Ambys Medicines, Boehringer Ingelheim, Gelesis, Mabwell Therapeutics, Surrozen, and Takeda; and as the founder/BOD/BEO of Nterica Bio.

A version of this article appeared on Medscape.com.

WASHINGTON — When a published case of auto-brewery syndrome (ABS) in China — caused by Klebsiella pneumoniae — received widespread publicity in 2019, patients reacted, sending emails to lead author Jing Yuan, in Beijing, China. Many of these inquiries were from patients in the United States who believed they might have ABS.

“Can you check to see if I have ABS?” patients asked Yuan.

For help, Yuan contacted Bernd Schnabl, MD, AGAF, at the University of California, San Diego, whose research was addressing alcohol-associated liver disease and who was also interested in the gut-liver axis and the role of gut microbiome–derived ethanol in metabolic dysfunction–associated steatotic liver disease (MASLD).

“She asked me, ‘Are you interested in looking into ABS?” Schnabl recalled at the Gut Microbiota for Health (GMFH) World Summit 2025. He dug in and formed what may be the largest research cohort thus far of patients with ABS — a group of 22 patients with their diagnosis confirmed through observed glucose challenge.

His soon-to-be-published research on this cohort has confirmed excess ethanol production — and elevations of both proteobacteria and fermentation pathways — in patients whose ABS symptoms had flared.

ABS is considered a rare condition, but “I’d argue that it’s rarely diagnosed because many physicians don’t know of the diagnosis, and many are actually very skeptical about the disease,” Schnabl said at the meeting, convened by AGA and the European Society of Neurogastroenterology and Motility.

Patients experience symptoms of intoxication when ethanol produced by dysregulated gut microbiota exceeds the capacity of the liver to metabolize it and accumulates in the blood, he explained.

“Patients constantly talk about brain fog; they can’t concentrate, and it can be very severe,” he said. “They don’t get a firm diagnosis and go from one medical center to another, and they also suffer from complications of alcohol use disorder including serious family, social, and legal problems.”

 

Advancing Knowledge, Findings From the Cohort

The phenomenon of ethanol production by gut microbiota has been known for over a century, Schnabl wrote with two co-authors in a 2024 review in Nature Reviews Gastroenterology & Hepatology of “endogenous ethanol production in health and disease.”

And in recent decades, he said at the meeting, research has linked endogenous ethanol production to MASLD, positioning it as a potential contributor to disease pathogenesis. In one of the most recently published studies, patients with MASLD had higher concentrations of ethanol in their systemic circulation after a mixed meal test than did healthy controls — and even higher ethanol concentrations in their portal vein blood, “suggesting that this ethanol is coming from the gut microbiome,” Schnabl said.

The paper from China that led Schnabl to establish his cohort was spurred on by a patient with both ABS and MASLD cirrhosis. The patient was found to have strains of high alcohol–producing K pneumoniae in the gut microbiome. When the researchers transplanted these strains into mice via fecal microbiota transplantation (FMT), the mice developed MASLD.

Schnabl’s study focused just on ABS, which is alternatively sometimes called gut fermentation syndrome. The 22 patients in his ABS cohort — each of whom provided stool samples corresponding to remission or flare of ABS symptoms — had a median age of 45 years and were predominantly men, slightly overweight and not obese, and without liver disease. (About 48 patients with suspected ABS were screened, and 20 were excluded after an observed glucose challenge failed to establish a diagnosis; 6 withdrew from the study.)

During remission (no symptoms), patients’ mean blood alcohol content (BAC) level was zero, but during a flare, the mean BAC level was 136 mg/dL. “To put it into perspective, the legal limit for driving in the US is 80 mg/dL,” Schnabl said. Within a mean of 4 hours after the oral glucose load used for diagnosis, patients’ mean BAC level was 73 mg/dL, he noted.

To assess ethanol production by the patients’ microbiota, Schnabl and his team cultured the stool samples — anaerobically adding glucose and measuring ethanol production — and compared the results with findings from stool samples collected from household partners who generally were of the opposite sex. Among their findings: cultures of stool from patients experiencing a flare produced significantly more ethanol than stool from household partners and samples from patients in remission.

To assess whether ethanol was produced by bacteria or fungi, the researchers measured ethanol production in cultures treated with either the antifungal amphotericin B or the antibiotic chloramphenicol. “Chloramphenicol clearly decreased the ethanol production,” Schnabl said. “So at least in this culture test, bacteria produced most of the alcohol in our patients.”

Taxonomic profiling, moreover, revealed “significantly elevated levels” of proteobacteria — with relative abundance of Escherichia coli and K pneumoniae — in patients who were flaring, he said. And functional profiling of the fecal microbiota showed much higher activity of fermentation pathways during patients’ flares than in household partners or healthy controls. (Healthy controls were incorporated into the taxonomic and functional profiling parts of the research.)

 

A Clinical Approach to ABS

Schnabl said at the meeting that stool cultures of both household partners and patients in long-term remission “all produced some low amount of ethanol, which was initially puzzling to us” but became less surprising as he and his colleagues reviewed more of the literature.

Asked during a discussion period whether ABS could explain chronic fatigue, a commonly reported chronic symptom in populations, Schnabl said it’s possible. And in an interview after the meeting, he elaborated. “The literature clearly says ABS is a rare disease, but I argue that more patients may have ABS; they just don’t know it. And I suspect some may have mild symptoms, like brain fog, feeling tired,” he said. “But at this point, this is complete speculation.”

Physicians should “be aware that if a patient has unexplained symptoms that could be aligned with ABS, checking the blood alcohol level” may be warranted, he said in the interview. A PEth (phosphatidylethanol) test — a biomarker test used to check for longer-term alcohol consumption — is an option, but it is important to appreciate it will not discriminate between exogenous alcohol drinking and endogenous ethanol production.

There are no standardized diagnostic tests for ABS, but at the meeting, Schnabl outlined a clinical approach, starting with a standardized oral glucose tolerance challenge test to detect elevated ethanol concentrations.

A fecal yeast test is warranted for diagnosed patients on the basis of some case reports in which ABS symptoms have improved with antifungal treatments. When the fecal yeast test is negative, “ideally you want to identify the ethanol-producing intestinal bacteria in the patient,” he said, using cultures and fecal metagenomics sequencing.

Treatment could then be tailored to the identified microbial strain, with options being selective antibiotics, probiotics and/or prebiotics, and — likely in the future — phages or FMT, he said. (These options, all aimed at restoring gut homeostasis, are also discussed in his 2024 review.)

Schnabl and his team recently performed FMT in a patient with ABS in whom E coli was determined to be producing excessive ethanol. The FMT, performed after antibiotic pretreatment, resulted in decreases in the relative abundance of proteobacteria and E coli levels, lower blood alcohol levels and fermentation enrichment pathways, and normalized liver enzymes.

After 6 months, however, the patient relapsed, and the measurements reversed. “We decided to do FMT every month, and we treated the patient for 6 months,” Schnabl said, noting that ABS had rendered the patient dysfunctional and unable to work. “He has been out of treatment for over a year now and is not flaring any longer.”

Schnabl and Elizabeth Hohmann, MD, at Massachusetts General Hospital, Boston, are currently recruiting patients with confirmed ABS for a National Institutes of Health–funded phase 1 safety and tolerability study of FMT for ABS.

Schnabl disclosed serving as an external scientific advisor/consultant to Ambys Medicines, Boehringer Ingelheim, Gelesis, Mabwell Therapeutics, Surrozen, and Takeda; and as the founder/BOD/BEO of Nterica Bio.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.

Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.

And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.

“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.

Among the current questions: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘New life’ for Phage Therapy

Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)

But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.

Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.

Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).

Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.

The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.

In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.

In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.

 

Other Niches for Therapeutic Phages, Challenges

Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.

In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.

Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.

And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.

Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.

In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.

Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.

 

A Window Into the Mycobiome

The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.

Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.

On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”

A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.

The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.

It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.

“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.

Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.

C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.

Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.

Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.

And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.

“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.

Among the current questions: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘New life’ for Phage Therapy

Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)

But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.

Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.

Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).

Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.

The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.

In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.

In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.

 

Other Niches for Therapeutic Phages, Challenges

Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.

In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.

Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.

And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.

Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.

In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.

Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.

 

A Window Into the Mycobiome

The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.

Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.

On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”

A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.

The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.

It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.

“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.

Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.

C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.

Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.

A version of this article appeared on Medscape.com.

WASHINGTON, DC — Research on the gut microbiome — and clinical attention to it — has focused mainly on bacteria, but bacteriophages and fungi play critical roles as well, with significant influences on health and disease, experts said at the Gut Microbiota for Health (GMFH) World Summit 2025.

Fungi account for < 1% of the total genetic material in the microbiome but 1%-2% of its total biomass. “Despite their relative rarity, they have an important and outsized influence on gut health” — an impact that results from their unique interface with the immune system, said Kyla Ost, PhD, of the Anschutz Medical Campus, University of Colorado, in Denver, whose research focuses on this interface.

And bacteriophages — viruses that infect and kill bacteria — are highly abundant in the gut. “Bacteriophages begin to colonize our GI [gastrointestinal] tract at the same time we develop our own microbiome shortly after birth, and from that time on, they interact with the bacteria in our GI tract, shaping [and being shaped by] the bacterial species we carry with us,” said Robert (Chip) Schooley, MD, distinguished professor of medicine at the University of California San Diego School of Medicine.

“We’ve been talking about things that affect the gut microbiome — diet, genetics, immune response — but probably the biggest influence on what grows in the GI tract are bacteriophages,” said Schooley, co-director of the Center for Innovative Phage Applications and Therapeutics, in a session on the extra-bacterial gut ecosystem.

Among the current questions: How can phages be used to manipulate the gut microbiome and influence GI-related diseases? And how can the pathogenic potential of commensal fungi be limited?

 

‘New life’ for Phage Therapy

Bacteriophages represent a promising approach for the treatment of multidrug resistant bacterial pathogens in an era of increasing resistance and a dried-up antibiotic discovery pipeline, Schooley said. (In 2019, an estimated 4.95 million deaths around the world were associated with bacterial antimicrobial resistance, and by 2050, it has been forecast that this number will rise to an estimated 8.22 million deaths.)

But in addition to suppressing bacterial pathogens causing direct morbidity, phage therapy has the potential to suppress bacteria believed to contribute to chronic diseases, he said. “We have proof-of-concept studies about the ability of phage to modulate bacteria in the digestive tract,” and an increasing number of clinical trials of the use of phages in GI and other diseases are underway, he said.

Phages were discovered just over a century ago, but phage therapy was widely abandoned once antibiotics were developed, except for in Russia and the former Eastern Bloc countries, where phage therapy continued to be used.

Phage therapy “got new life” in the West, Schooley said, about 10-15 years ago with an increasing number of detailed and high-profile case reports, including one in which a UC San Diego colleague, Tom Patterson, PhD, contracted a deadly multidrug resistant bacterial infection in Egypt and was eventually saved with bacteriophage therapy. (The case was the subject of the book The Perfect Predator).

Since then, as described in case reports and studies in the literature, “hundreds of people have been treated with bacteriophages here and in Europe,” most commonly for pulmonary infections and infections in implanted vascular and orthopedic devices, said Schooley, who coauthored a review in Cell in 2023 that describes phage biology and advances and future directions in phage therapy.

The use of bacteriophages to prevent systemic infections during high-risk periods — such as during chemotherapeutic regimens for hematological regimens — is an area of interest, he said at the meeting.

In research that is making its way to a clinical trial of patients undergoing allogeneic hematopoietic stem cell transplant (HSCT), researchers screened a library of phages to identify those with broad coverage of Escherichia coli. Using tail fiber engineering and CRISPR technology, they then engineered a combination of the four most complementary bacteriophages to selectively kill E coli — including fluoroquinolone-resistant strains that, in patients whose GI tracts are colonized with these strains, can translocate from the gut into the bloodstream, causing sepsis, during chemotherapeutic regimens for HSCT.

In a mouse model, the CRISPR-enhanced four-phage cocktail (SNIPR001) led to a steady reduction in the E coli colony counts in stool, “showing you can modulate these bacteria in the gut by using bacteriophages to kill them,” Schooley said. Moreover, the CRISPR enhancement strengthened the phages’ ability to break up biofilms, he said, showing “that you can engineer bacteriophages to make them better killers.” A phase 1b/2a study is being planned.

 

Other Niches for Therapeutic Phages, Challenges

Bacteriophages also could be used to target a gut bacterium that has been shown to attenuate alcoholic liver disease. Patients with alcoholic hepatitis “have a gut microbiome that is different in distribution,” Schooley said, often with increased numbers of Enterococcus faecalis that produce cytolysin, an exotoxin that exacerbates liver injury and is associated with increased mortality.

In published research led by investigators at UC San Diego, stool from cytolysin-positive patients with alcoholic hepatitis was found to exacerbate ethanol-induced liver disease in gnotobiotic mice, and phage therapy against cytolytic E faecalis was found to abolish it, Schooley shared.

Research is also exploring the potential of phage therapy to selectively target adherent invasive E coli in Crohn’s disease, and Klebsiella pneumoniae in the gut microbiome as an exacerbator of inflammatory bowel disease (IBD), he said.

And investigators in Japan, he noted, have reported that bacteriophage therapy against K pneumoniae can ameliorate liver inflammation and disease severity in primary sclerosing cholangitis.

Challenges in the therapeutic use of phages include the narrow host range of phages and an uncertain predictive value of in vitro phage susceptibility testing. “We don’t know yet how to do resistance testing as well as we do with antibiotics,” he said.

In addition, most phages tend to be acid labile, requiring strategies to mitigate inactivation by gastric acid, and there are “major knowledge gaps” relating to phage pharmacology. “We also know that adaptive immune responses to phages can but often doesn’t impact therapy, and we want to understand that better in clinical trials,” Schooley said.

Phages that have a “lysogenic” lifestyle — as opposed to lytic phages which are used therapeutically — can contribute to antibiotic resistance by facilitating the interchange of bacterial resistance genes, he noted.

 

A Window Into the Mycobiome

The human gut mycobiome is primarily composed of fungi in the Saccharomyces, Candida, and Malassezia genera, with Candida species dominating. Fungal cells harbor distinct immune-stimulatory molecules and activate distinct immune pathways compared with bacteria and other members of the microbiome, said Ost, assistant professor in the immunology and microbiology department of CU Anschutz.

Some fungi, including those in the Candida genus, activate adaptive and innate immune responses that promote metabolic health and protect against infection. A recently published study in Science, for instance, demonstrated that colonization with C dubliniensis in very young mice who had been exposed to broad-spectrum antibiotics promoted “the expansion and development of beta cells in the pancreas” in a macrophage dependent manner, improving metabolic health and reducing diabetes incidence, she shared.

On the one hand, fungi can “exacerbate and perpetuate the pathogenic inflammation that’s found in a growing list of inflammatory diseases” such as IBD. And “in fact, a lot of the benefits and detriments are driven by the exact same species of fungi,” said Ost. “This is particularly true of Candida,” which is a “lifelong colonizer of intestinal microbiota that rarely causes disease but can be quite pathogenic when it does.”

A 2023 review in Nature Reviews Gastroenterology & Hepatology coauthored by Ost describes the role of commensal fungi in intestinal diseases, including IBD, colorectal cancer, and pancreatic cancer.

The pathogenic potential of commensal fungi is largely dependent on its strain, its morphology and its expression of virulence factors, researchers are learning. Ost has studied C albicans, which has been associated with intestinal inflammation and IBD. Like some other Candida species, C albicans are “fascinating shape shifters,” she said, transitioning between a less pathogenic “yeast” morphology and an elongated, adhesive “hyphae” shape that is more pathogenic.

It turns out, according to research by Ost and others, that the C albicans hyphal morphotype — and the adhesins (sticky proteins that facilitate adherence to epithelial cells) and a cytolytic toxin it produces — are preferentially targeted and suppressed by immunoglobulin A (IgA) in the gut.

“Our gut is protected by a large quantity of IgA antibodies…and these IgA interact with the microbiota and play a big role in what microbes are there and the biology of the microbes,” Ost said. Indeed, symptomatic IgA deficiency in humans has been shown to be associated with C albicans overgrowth.

Leveraging the hyphal-specific IgA response to protect against disease seems possible, she said, referring to an experimental anti-Candida fungal vaccine (NDV-3A) designed to induce an adhesin-specific immune response. In a mouse model of colitis, the vaccine protected against C albicans-associated damage. “We saw an immediate IgA response that targeted C albicans in the intestinal contents,” Ost said.

C glabrata, which has also been associated with intestinal inflammation and IBD, does not form hyphae but — depending on the strain — may also induce intestinal IgA responses, she said in describing her recent research.

Ost reported having no disclosures. Schooley disclosed being a consultant for SNIPR Biome, BiomX, Locus, MicrobiotiX, Amazon Data Monitoring Committee: Merck.

A version of this article appeared on Medscape.com.

US counties with limited access to healthy food (food deserts) or a high density of unhealthy food outlets (food swamps) have higher mortality rates from metabolic dysfunction–associated steatotic liver disease (MASLD), according to investigators.

These findings highlight the importance of addressing disparities in food environments and social determinants of health to help reduce MASLD-related mortality, lead author Annette Paik, MD, of Inova Health System, Falls Church, Virginia, and colleagues reported.

“Recent studies indicate that food swamps and deserts, as surrogates for food insecurity, are linked to poor glycemic control and higher adult obesity rates,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Understanding the intersection of these factors with sociodemographic and clinical variables offers insights into MASLD-related outcomes, including mortality.”

To this end, the present study examined the association between food environments and MASLD-related mortality across more than 2,195 US counties. County-level mortality data were obtained from the CDC WONDER database (2016-2020) and linked to food environment data from the US Department of Agriculture Food Environment Atlas using Federal Information Processing Standards (FIPS) codes. Food deserts were defined as low-income areas with limited access to grocery stores, while food swamps were characterized by a predominance of unhealthy food outlets relative to healthy ones.

Additional data on obesity, type 2 diabetes (T2D), and nine social determinants of health were obtained from CDC PLACES and other publicly available datasets. Counties were stratified into quartiles based on MASLD-related mortality rates. Population-weighted mixed-effects linear regression models were used to evaluate associations between food environment exposures and MASLD mortality, adjusting for region, rural-urban status, age, sex, race, insurance coverage, chronic dis-ease prevalence, SNAP participation, and access to exercise facilities.

Counties with the worst food environments had significantly higher MASLD-related mortality, even after adjusting for clinical and sociodemographic factors. Compared with counties in the lowest quartile of MASLD mortality, those in the highest quartile had a greater proportion of food deserts (22.3% vs 14.9%; P < .001) and food swamps (73.1% vs 65.7%; P < .001). They also had a significantly higher prevalence of obesity (40.5% vs 32.5%), type 2 diabetes (15.8% vs 11.4%), and physical inactivity (33.7% vs 24.9%).

Demographically, counties with higher MASLD mortality had significantly larger proportions of Black and Hispanic residents, and were more likely to be rural and located in the South. These counties also had significantly lower median household incomes, higher poverty rates, fewer adults with a college education, lower access to exercise opportunities, greater SNAP participation, less broadband access, and more uninsured adults.

In multivariable regression models, both food deserts and food swamps remained independently associated with MASLD mortality. Counties in the highest quartile of food desert exposure had a 14.5% higher MASLD mortality rate, compared with the lowest quartile (P = .001), and those in the highest quartile for food swamp exposure had a 13.9% higher mortality rate (P = .005).

Type 2 diabetes, physical inactivity, and lack of health insurance were also independently associated with increased MASLD-related mortality. 

“Implementing public health interventions that address the specific environmental factors of each county can help US policymakers promote access to healthy, culturally appropriate food choices at affordable prices and reduce the consumption of poor-quality food,” the investigators wrote. “Moreover, improving access to parks and exercise facilities can further enhance the impact of healthy nutrition. These strategies could help curb the growing epidemic of metabolic diseases, including MASLD and related mortality.”

This study was supported by King Faisal Specialist Hospital & Research Center, the Global NASH Council, Center for Outcomes Research in Liver Diseases, and the Beatty Liver and Obesity Research Fund, Inova Health System. The investigators disclosed no conflicts of interest.
 

US counties with limited access to healthy food (food deserts) or a high density of unhealthy food outlets (food swamps) have higher mortality rates from metabolic dysfunction–associated steatotic liver disease (MASLD), according to investigators.

These findings highlight the importance of addressing disparities in food environments and social determinants of health to help reduce MASLD-related mortality, lead author Annette Paik, MD, of Inova Health System, Falls Church, Virginia, and colleagues reported.

“Recent studies indicate that food swamps and deserts, as surrogates for food insecurity, are linked to poor glycemic control and higher adult obesity rates,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Understanding the intersection of these factors with sociodemographic and clinical variables offers insights into MASLD-related outcomes, including mortality.”

To this end, the present study examined the association between food environments and MASLD-related mortality across more than 2,195 US counties. County-level mortality data were obtained from the CDC WONDER database (2016-2020) and linked to food environment data from the US Department of Agriculture Food Environment Atlas using Federal Information Processing Standards (FIPS) codes. Food deserts were defined as low-income areas with limited access to grocery stores, while food swamps were characterized by a predominance of unhealthy food outlets relative to healthy ones.

Additional data on obesity, type 2 diabetes (T2D), and nine social determinants of health were obtained from CDC PLACES and other publicly available datasets. Counties were stratified into quartiles based on MASLD-related mortality rates. Population-weighted mixed-effects linear regression models were used to evaluate associations between food environment exposures and MASLD mortality, adjusting for region, rural-urban status, age, sex, race, insurance coverage, chronic dis-ease prevalence, SNAP participation, and access to exercise facilities.

Counties with the worst food environments had significantly higher MASLD-related mortality, even after adjusting for clinical and sociodemographic factors. Compared with counties in the lowest quartile of MASLD mortality, those in the highest quartile had a greater proportion of food deserts (22.3% vs 14.9%; P < .001) and food swamps (73.1% vs 65.7%; P < .001). They also had a significantly higher prevalence of obesity (40.5% vs 32.5%), type 2 diabetes (15.8% vs 11.4%), and physical inactivity (33.7% vs 24.9%).

Demographically, counties with higher MASLD mortality had significantly larger proportions of Black and Hispanic residents, and were more likely to be rural and located in the South. These counties also had significantly lower median household incomes, higher poverty rates, fewer adults with a college education, lower access to exercise opportunities, greater SNAP participation, less broadband access, and more uninsured adults.

In multivariable regression models, both food deserts and food swamps remained independently associated with MASLD mortality. Counties in the highest quartile of food desert exposure had a 14.5% higher MASLD mortality rate, compared with the lowest quartile (P = .001), and those in the highest quartile for food swamp exposure had a 13.9% higher mortality rate (P = .005).

Type 2 diabetes, physical inactivity, and lack of health insurance were also independently associated with increased MASLD-related mortality. 

“Implementing public health interventions that address the specific environmental factors of each county can help US policymakers promote access to healthy, culturally appropriate food choices at affordable prices and reduce the consumption of poor-quality food,” the investigators wrote. “Moreover, improving access to parks and exercise facilities can further enhance the impact of healthy nutrition. These strategies could help curb the growing epidemic of metabolic diseases, including MASLD and related mortality.”

This study was supported by King Faisal Specialist Hospital & Research Center, the Global NASH Council, Center for Outcomes Research in Liver Diseases, and the Beatty Liver and Obesity Research Fund, Inova Health System. The investigators disclosed no conflicts of interest.
 

US counties with limited access to healthy food (food deserts) or a high density of unhealthy food outlets (food swamps) have higher mortality rates from metabolic dysfunction–associated steatotic liver disease (MASLD), according to investigators.

These findings highlight the importance of addressing disparities in food environments and social determinants of health to help reduce MASLD-related mortality, lead author Annette Paik, MD, of Inova Health System, Falls Church, Virginia, and colleagues reported.

“Recent studies indicate that food swamps and deserts, as surrogates for food insecurity, are linked to poor glycemic control and higher adult obesity rates,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Understanding the intersection of these factors with sociodemographic and clinical variables offers insights into MASLD-related outcomes, including mortality.”

To this end, the present study examined the association between food environments and MASLD-related mortality across more than 2,195 US counties. County-level mortality data were obtained from the CDC WONDER database (2016-2020) and linked to food environment data from the US Department of Agriculture Food Environment Atlas using Federal Information Processing Standards (FIPS) codes. Food deserts were defined as low-income areas with limited access to grocery stores, while food swamps were characterized by a predominance of unhealthy food outlets relative to healthy ones.

Additional data on obesity, type 2 diabetes (T2D), and nine social determinants of health were obtained from CDC PLACES and other publicly available datasets. Counties were stratified into quartiles based on MASLD-related mortality rates. Population-weighted mixed-effects linear regression models were used to evaluate associations between food environment exposures and MASLD mortality, adjusting for region, rural-urban status, age, sex, race, insurance coverage, chronic dis-ease prevalence, SNAP participation, and access to exercise facilities.

Counties with the worst food environments had significantly higher MASLD-related mortality, even after adjusting for clinical and sociodemographic factors. Compared with counties in the lowest quartile of MASLD mortality, those in the highest quartile had a greater proportion of food deserts (22.3% vs 14.9%; P < .001) and food swamps (73.1% vs 65.7%; P < .001). They also had a significantly higher prevalence of obesity (40.5% vs 32.5%), type 2 diabetes (15.8% vs 11.4%), and physical inactivity (33.7% vs 24.9%).

Demographically, counties with higher MASLD mortality had significantly larger proportions of Black and Hispanic residents, and were more likely to be rural and located in the South. These counties also had significantly lower median household incomes, higher poverty rates, fewer adults with a college education, lower access to exercise opportunities, greater SNAP participation, less broadband access, and more uninsured adults.

In multivariable regression models, both food deserts and food swamps remained independently associated with MASLD mortality. Counties in the highest quartile of food desert exposure had a 14.5% higher MASLD mortality rate, compared with the lowest quartile (P = .001), and those in the highest quartile for food swamp exposure had a 13.9% higher mortality rate (P = .005).

Type 2 diabetes, physical inactivity, and lack of health insurance were also independently associated with increased MASLD-related mortality. 

“Implementing public health interventions that address the specific environmental factors of each county can help US policymakers promote access to healthy, culturally appropriate food choices at affordable prices and reduce the consumption of poor-quality food,” the investigators wrote. “Moreover, improving access to parks and exercise facilities can further enhance the impact of healthy nutrition. These strategies could help curb the growing epidemic of metabolic diseases, including MASLD and related mortality.”

This study was supported by King Faisal Specialist Hospital & Research Center, the Global NASH Council, Center for Outcomes Research in Liver Diseases, and the Beatty Liver and Obesity Research Fund, Inova Health System. The investigators disclosed no conflicts of interest.
 

Only 1 in 6 US veterans with chronic hepatitis B (CHB) is tested for hepatitis D virus (HDV)—a coinfection associated with significantly higher risks of cirrhosis and hepatic decompensation—according to new findings.

The low testing rate suggests limited awareness of HDV-associated risks in patients with CHB, and underscores the need for earlier testing and diagnosis, lead author Robert J. Wong, MD, of Stanford University School of Medicine, Stanford, California, and colleagues, reported.

“Data among US populations are lacking to describe the epidemiology and long-term outcomes of patients with CHB and concurrent HDV infection,” the investigators wrote in Gastro Hep Advances (2025 Oct. doi: 10.1016/j.gastha.2024.10.015).

Prior studies have found that only 6% to 19% of patients with CHB get tested for HDV, and among those tested, the prevalence is relatively low—between 2% and 4.6%. Although relatively uncommon, HDV carries a substantial clinical and economic burden, Dr. Wong and colleagues noted, highlighting the importance of clinical awareness and accurate epidemiologic data.

The present study analyzed data from the Veterans Affairs (VA) Corporate Data Warehouse between 2010 and 2023. Adults with CHB were identified based on laboratory-confirmed markers and ICD-9/10 codes. HDV testing (anti-HDV antibody and HDV RNA) was assessed, and predictors of testing were evaluated using multivariable logistic regression.

To examine liver-related outcomes, patients who tested positive for HDV were propensity score–matched 1:2 with CHB patients who tested negative. Matching accounted for age, sex, race/ethnicity, HBeAg status, antiviral treatment, HCV and HIV coinfection, diabetes, and alcohol use. Patients with cirrhosis or hepatocellular carcinoma (HCC) at base-line were excluded. Incidence of cirrhosis, hepatic decompensation, and HCC was estimated using competing risks Nelson-Aalen methods.

Among 27,548 veterans with CHB, only 16.1% underwent HDV testing. Of those tested, 3.25% were HDV positive. Testing rates were higher among patients who were HBeAg positive, on antiviral therapy, or identified as Asian or Pacific Islander.

Conversely, testing was significantly less common among patients with high-risk alcohol use, past or current drug use, cirrhosis at diagnosis, or HCV coinfection. In contrast, HIV coinfection was associated with increased odds of being tested.

Among those tested, HDV positivity was more likely in patients with HCV coinfection, cirrhosis, or a history of drug use. On multivariable analysis, these factors were independent predictors of HDV positivity.

In the matched cohort of 71 HDV-positive patients and 140 HDV-negative controls, the incidence of cirrhosis was more than 3-fold higher in HDV-positive patients (4.39 vs 1.30 per 100,000 person-years; P less than .01), and hepatic decompensation was over 5 times more common (2.18 vs 0.41 per 100,000 person-years; P = .01). There was also a non-significant trend toward increased HCC risk in the HDV group.

“These findings align with existing studies and confirm that among a predominantly non-Asian US cohort of CHB patients, presence of concurrent HDV is associated with more severe liver disease progression,” the investigators wrote. “These observations, taken together with the low rates of HDV testing overall and particularly among high-risk individuals, emphasizes the need for greater awareness and novel strategies on how to improve HDV testing and diagnosis, particularly given that novel HDV therapies are on the near horizon.”

The study was supported by Gilead. The investigators disclosed additional relationships with Exact Sciences, GSK, Novo Nordisk, and others.

Only 1 in 6 US veterans with chronic hepatitis B (CHB) is tested for hepatitis D virus (HDV)—a coinfection associated with significantly higher risks of cirrhosis and hepatic decompensation—according to new findings.

The low testing rate suggests limited awareness of HDV-associated risks in patients with CHB, and underscores the need for earlier testing and diagnosis, lead author Robert J. Wong, MD, of Stanford University School of Medicine, Stanford, California, and colleagues, reported.

“Data among US populations are lacking to describe the epidemiology and long-term outcomes of patients with CHB and concurrent HDV infection,” the investigators wrote in Gastro Hep Advances (2025 Oct. doi: 10.1016/j.gastha.2024.10.015).

Prior studies have found that only 6% to 19% of patients with CHB get tested for HDV, and among those tested, the prevalence is relatively low—between 2% and 4.6%. Although relatively uncommon, HDV carries a substantial clinical and economic burden, Dr. Wong and colleagues noted, highlighting the importance of clinical awareness and accurate epidemiologic data.

The present study analyzed data from the Veterans Affairs (VA) Corporate Data Warehouse between 2010 and 2023. Adults with CHB were identified based on laboratory-confirmed markers and ICD-9/10 codes. HDV testing (anti-HDV antibody and HDV RNA) was assessed, and predictors of testing were evaluated using multivariable logistic regression.

To examine liver-related outcomes, patients who tested positive for HDV were propensity score–matched 1:2 with CHB patients who tested negative. Matching accounted for age, sex, race/ethnicity, HBeAg status, antiviral treatment, HCV and HIV coinfection, diabetes, and alcohol use. Patients with cirrhosis or hepatocellular carcinoma (HCC) at base-line were excluded. Incidence of cirrhosis, hepatic decompensation, and HCC was estimated using competing risks Nelson-Aalen methods.

Among 27,548 veterans with CHB, only 16.1% underwent HDV testing. Of those tested, 3.25% were HDV positive. Testing rates were higher among patients who were HBeAg positive, on antiviral therapy, or identified as Asian or Pacific Islander.

Conversely, testing was significantly less common among patients with high-risk alcohol use, past or current drug use, cirrhosis at diagnosis, or HCV coinfection. In contrast, HIV coinfection was associated with increased odds of being tested.

Among those tested, HDV positivity was more likely in patients with HCV coinfection, cirrhosis, or a history of drug use. On multivariable analysis, these factors were independent predictors of HDV positivity.

In the matched cohort of 71 HDV-positive patients and 140 HDV-negative controls, the incidence of cirrhosis was more than 3-fold higher in HDV-positive patients (4.39 vs 1.30 per 100,000 person-years; P less than .01), and hepatic decompensation was over 5 times more common (2.18 vs 0.41 per 100,000 person-years; P = .01). There was also a non-significant trend toward increased HCC risk in the HDV group.

“These findings align with existing studies and confirm that among a predominantly non-Asian US cohort of CHB patients, presence of concurrent HDV is associated with more severe liver disease progression,” the investigators wrote. “These observations, taken together with the low rates of HDV testing overall and particularly among high-risk individuals, emphasizes the need for greater awareness and novel strategies on how to improve HDV testing and diagnosis, particularly given that novel HDV therapies are on the near horizon.”

The study was supported by Gilead. The investigators disclosed additional relationships with Exact Sciences, GSK, Novo Nordisk, and others.

Only 1 in 6 US veterans with chronic hepatitis B (CHB) is tested for hepatitis D virus (HDV)—a coinfection associated with significantly higher risks of cirrhosis and hepatic decompensation—according to new findings.

The low testing rate suggests limited awareness of HDV-associated risks in patients with CHB, and underscores the need for earlier testing and diagnosis, lead author Robert J. Wong, MD, of Stanford University School of Medicine, Stanford, California, and colleagues, reported.

“Data among US populations are lacking to describe the epidemiology and long-term outcomes of patients with CHB and concurrent HDV infection,” the investigators wrote in Gastro Hep Advances (2025 Oct. doi: 10.1016/j.gastha.2024.10.015).

Prior studies have found that only 6% to 19% of patients with CHB get tested for HDV, and among those tested, the prevalence is relatively low—between 2% and 4.6%. Although relatively uncommon, HDV carries a substantial clinical and economic burden, Dr. Wong and colleagues noted, highlighting the importance of clinical awareness and accurate epidemiologic data.

The present study analyzed data from the Veterans Affairs (VA) Corporate Data Warehouse between 2010 and 2023. Adults with CHB were identified based on laboratory-confirmed markers and ICD-9/10 codes. HDV testing (anti-HDV antibody and HDV RNA) was assessed, and predictors of testing were evaluated using multivariable logistic regression.

To examine liver-related outcomes, patients who tested positive for HDV were propensity score–matched 1:2 with CHB patients who tested negative. Matching accounted for age, sex, race/ethnicity, HBeAg status, antiviral treatment, HCV and HIV coinfection, diabetes, and alcohol use. Patients with cirrhosis or hepatocellular carcinoma (HCC) at base-line were excluded. Incidence of cirrhosis, hepatic decompensation, and HCC was estimated using competing risks Nelson-Aalen methods.

Among 27,548 veterans with CHB, only 16.1% underwent HDV testing. Of those tested, 3.25% were HDV positive. Testing rates were higher among patients who were HBeAg positive, on antiviral therapy, or identified as Asian or Pacific Islander.

Conversely, testing was significantly less common among patients with high-risk alcohol use, past or current drug use, cirrhosis at diagnosis, or HCV coinfection. In contrast, HIV coinfection was associated with increased odds of being tested.

Among those tested, HDV positivity was more likely in patients with HCV coinfection, cirrhosis, or a history of drug use. On multivariable analysis, these factors were independent predictors of HDV positivity.

In the matched cohort of 71 HDV-positive patients and 140 HDV-negative controls, the incidence of cirrhosis was more than 3-fold higher in HDV-positive patients (4.39 vs 1.30 per 100,000 person-years; P less than .01), and hepatic decompensation was over 5 times more common (2.18 vs 0.41 per 100,000 person-years; P = .01). There was also a non-significant trend toward increased HCC risk in the HDV group.

“These findings align with existing studies and confirm that among a predominantly non-Asian US cohort of CHB patients, presence of concurrent HDV is associated with more severe liver disease progression,” the investigators wrote. “These observations, taken together with the low rates of HDV testing overall and particularly among high-risk individuals, emphasizes the need for greater awareness and novel strategies on how to improve HDV testing and diagnosis, particularly given that novel HDV therapies are on the near horizon.”

The study was supported by Gilead. The investigators disclosed additional relationships with Exact Sciences, GSK, Novo Nordisk, and others.

Long-term use of statins may delay or deflect the development of hepatocellular carcinoma in adults with chronic liver disease, as well as in the general population, emerging research, including several large cohort studies, suggested.

The most recent study, published in JAMA Internal Medicine, showed a lower incidence of hepatic decompensation among statin users in a registry for adults aged 40 years or older with baseline chronic liver disease.

“Our findings support the idea that statins may offer benefits beyond lipid-lowering in patients with [chronic liver disease], and clinicians may be more confident in prescribing statins when indicated,” even in these patients, said corresponding Co-author Raymond T. Chung, MD, gastroenterology investigator at Mass General Research Institute, Boston, in an interview. 

“While prior studies have suggested an association between statin use and reduced hepatocellular carcinoma risk, our study aimed to build on that evidence by using a large, real-world, hospital-based cohort inclusive of all etiologies of chronic liver disease,” Chung told GI & Hepatology News.

Chung, along with Jonggi Choi, MD, of the University of Ulsan College of Medicine, Seoul, South Korea, and colleagues, reviewed data from the Research Patient Data Registry from 2000 to 2023 for 16,501 participantsaged 40 years or older with baseline chronic liver disease and baseline Fibrosis-4 (FIB-4) scores ≥ 1.3.

The study population had a mean age of 59.7 years, and 40.9% were women. The researchers divided the population into statin users (n = 3610) and nonusers (n = 12,891). Statin use was defined as a cumulative defined daily dose ≥ 30 mg.

The primary outcome was the cumulative incidence of hepatocellular carcinoma and hepatic decompensation.

At 10 years follow-up, statin users showed a significantly reduced incidence of hepatocellular carcinoma vs nonusers (3.8% vs 8.0%; P < .001) as well as a significantly reduced incidence of hepatic decompensation (10.6% vs 19.5%; P < .001).

Incorporating FIB-4 scores, a surrogate marker for liver fibrosis, also showed that statin users were less likely to experience fibrosis progression, offering a potential mechanism of action for the observed reduction in adverse liver outcomes, Chung told GI & Hepatology News.

“Similar trends have been observed in prior observational studies, but our findings now support a real effect of statin use on fibrosis progression,” he said. “However, what strengthened our study was that the association remained consistent across multiple subgroups and sensitivity analyses.”

Another study published in Clinical Gastroenterology and Hepatology showed a reduced risk of developing severe liver disease in a Swedish cohort of noncirrhotic adults with chronic liver disease who used statins (n = 3862) compared with control patients with chronic liver disease (matched 1:1) and who did not use statins (hazard ratio [HR], 0.60). 

In that study, Rajani Sharma, MD, and colleagues found a protective association in both prefibrosis and fibrosis stages at diagnosis, and statin use was associated with reduced rates of progression to both cirrhosis and hepatocellular carcinoma (HR, 0.62 and 0.44, respectively).

 

Exciting and Necessary Research

The research by Choi and colleagues is “exciting,” said Bubu Banini, MD, PhD, an assistant professor in digestive diseases at Yale School of Medicine, New Haven, Connecticut, in an interview.

Liver cancer prevalence has risen over the past few decades in the United States and worldwide, and the 5-year overall survival rate of liver cancer is less than 20%, Banini told GI & Hepatology News.

Clinicians often withhold statins out of fear of liver injury in persons with chronic liver disease; however, a takeaway from this study is that for persons with chronic liver disease who have indications for statin use, the medication should not be withheld, she said.

Of course, prospective studies are needed to replicate the results, Banini added.

The study findings were limited by several factors, including the inability to adjust for all potential confounding variables, lack of data on post-index treatments, and the use of wide, cumulative, defined daily dose categories to ensure statistical power, the researchers noted.

“Moving forward, randomized controlled trials are essential to establish a causal relationship and clarify the molecular and clinical pathways through which statins exert hepatoprotective effects,” Chung added.

Randomized controlled trials are also needed to determine whether statins can actually reduce the risk for hepatocellular carcinoma and hepatic decompensation in patients with chronic liver disease, and cost-effectiveness analyses may be essential for translating this evidence into clinical guidelines, he added.

 

Statins and HCC Risk in the General Population

A large cohort study, published in JAMA Network Open by Mara Sophie Vell, PhD, and colleagues, showed an association between reduced risk for hepatocellular carcinoma and statin use in the general population and in those at increased risk for liver disease.

The study, which included data for individuals aged 37-73 years from the UK Biobank, found a 15% reduced risk for new-onset liver disease and a 28% reduced risk for liver-related death among regular statin users than among nonusers (HR, 0.85 and 0.72, respectively). 

In addition, regular statin users showed a 74% reduced risk (P = .003) of developing hepatocellular carcinoma compared with those not using statins. The researchers identified a particular impact on liver disease risk reduction among men, individuals with diabetes, and patients with high levels of liver scarring at baseline based on the FIB-4 index.

A meta-analysis of 24 studies, previously published in the journal Cancers, showed a significant reduction of 46% in hepatocellular carcinoma risk among statins users compared with nonusers.

The researchers found this risk reduction was significant in subgroups of patients with diabetes, liver cirrhosis, and those on antiviral therapy, and they suggested that the antiangiogenic, immunomodulatory, antiproliferative, and antifibrotic properties of statins may contribute to their potential to reduce tumor growth or hepatocellular carcinoma development.

The meta-analysis authors noted that although most studies have reported a low risk for statin-induced hepatotoxicity, clinicians should proceed with caution in some patients with existing cirrhosis.

“If the patients are diagnosed with decompensated cirrhosis, then statins should be prescribed with caution at low doses,” they wrote.

Advocating statin use solely for chemoprevention may be premature based on observational data, Chung told GI & Hepatology News.

“However, in patients with [chronic liver disease] who already meet indications for statin therapy, the potential added benefit of reducing liver-related complications strengthens the rationale for their use,” he said. Future randomized clinical trials will be key to defining the risk-benefit profile in this context.

The study by Choi and colleagues was supported by the National Institutes of Health.

The study by Sharma and colleagues was supported by the Karolinska Institutet, Stockholm, Sweden, and the Columbia University Irving Medical Center, New York City; researchers were supported by grants from the Swedish Research Council, Center for Innovative Medicine, the Swedish Cancer Society, and the National Institutes of Health.

The study by Vell and colleagues had no outside funding.

The study by Mohaimenul Islam and colleagues was supported by the Ministry of Education and Ministry of Science and Technology, Taiwan.

Chung and Banini had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Long-term use of statins may delay or deflect the development of hepatocellular carcinoma in adults with chronic liver disease, as well as in the general population, emerging research, including several large cohort studies, suggested.

The most recent study, published in JAMA Internal Medicine, showed a lower incidence of hepatic decompensation among statin users in a registry for adults aged 40 years or older with baseline chronic liver disease.

“Our findings support the idea that statins may offer benefits beyond lipid-lowering in patients with [chronic liver disease], and clinicians may be more confident in prescribing statins when indicated,” even in these patients, said corresponding Co-author Raymond T. Chung, MD, gastroenterology investigator at Mass General Research Institute, Boston, in an interview. 

“While prior studies have suggested an association between statin use and reduced hepatocellular carcinoma risk, our study aimed to build on that evidence by using a large, real-world, hospital-based cohort inclusive of all etiologies of chronic liver disease,” Chung told GI & Hepatology News.

Chung, along with Jonggi Choi, MD, of the University of Ulsan College of Medicine, Seoul, South Korea, and colleagues, reviewed data from the Research Patient Data Registry from 2000 to 2023 for 16,501 participantsaged 40 years or older with baseline chronic liver disease and baseline Fibrosis-4 (FIB-4) scores ≥ 1.3.

The study population had a mean age of 59.7 years, and 40.9% were women. The researchers divided the population into statin users (n = 3610) and nonusers (n = 12,891). Statin use was defined as a cumulative defined daily dose ≥ 30 mg.

The primary outcome was the cumulative incidence of hepatocellular carcinoma and hepatic decompensation.

At 10 years follow-up, statin users showed a significantly reduced incidence of hepatocellular carcinoma vs nonusers (3.8% vs 8.0%; P < .001) as well as a significantly reduced incidence of hepatic decompensation (10.6% vs 19.5%; P < .001).

Incorporating FIB-4 scores, a surrogate marker for liver fibrosis, also showed that statin users were less likely to experience fibrosis progression, offering a potential mechanism of action for the observed reduction in adverse liver outcomes, Chung told GI & Hepatology News.

“Similar trends have been observed in prior observational studies, but our findings now support a real effect of statin use on fibrosis progression,” he said. “However, what strengthened our study was that the association remained consistent across multiple subgroups and sensitivity analyses.”

Another study published in Clinical Gastroenterology and Hepatology showed a reduced risk of developing severe liver disease in a Swedish cohort of noncirrhotic adults with chronic liver disease who used statins (n = 3862) compared with control patients with chronic liver disease (matched 1:1) and who did not use statins (hazard ratio [HR], 0.60). 

In that study, Rajani Sharma, MD, and colleagues found a protective association in both prefibrosis and fibrosis stages at diagnosis, and statin use was associated with reduced rates of progression to both cirrhosis and hepatocellular carcinoma (HR, 0.62 and 0.44, respectively).

 

Exciting and Necessary Research

The research by Choi and colleagues is “exciting,” said Bubu Banini, MD, PhD, an assistant professor in digestive diseases at Yale School of Medicine, New Haven, Connecticut, in an interview.

Liver cancer prevalence has risen over the past few decades in the United States and worldwide, and the 5-year overall survival rate of liver cancer is less than 20%, Banini told GI & Hepatology News.

Clinicians often withhold statins out of fear of liver injury in persons with chronic liver disease; however, a takeaway from this study is that for persons with chronic liver disease who have indications for statin use, the medication should not be withheld, she said.

Of course, prospective studies are needed to replicate the results, Banini added.

The study findings were limited by several factors, including the inability to adjust for all potential confounding variables, lack of data on post-index treatments, and the use of wide, cumulative, defined daily dose categories to ensure statistical power, the researchers noted.

“Moving forward, randomized controlled trials are essential to establish a causal relationship and clarify the molecular and clinical pathways through which statins exert hepatoprotective effects,” Chung added.

Randomized controlled trials are also needed to determine whether statins can actually reduce the risk for hepatocellular carcinoma and hepatic decompensation in patients with chronic liver disease, and cost-effectiveness analyses may be essential for translating this evidence into clinical guidelines, he added.

 

Statins and HCC Risk in the General Population

A large cohort study, published in JAMA Network Open by Mara Sophie Vell, PhD, and colleagues, showed an association between reduced risk for hepatocellular carcinoma and statin use in the general population and in those at increased risk for liver disease.

The study, which included data for individuals aged 37-73 years from the UK Biobank, found a 15% reduced risk for new-onset liver disease and a 28% reduced risk for liver-related death among regular statin users than among nonusers (HR, 0.85 and 0.72, respectively). 

In addition, regular statin users showed a 74% reduced risk (P = .003) of developing hepatocellular carcinoma compared with those not using statins. The researchers identified a particular impact on liver disease risk reduction among men, individuals with diabetes, and patients with high levels of liver scarring at baseline based on the FIB-4 index.

A meta-analysis of 24 studies, previously published in the journal Cancers, showed a significant reduction of 46% in hepatocellular carcinoma risk among statins users compared with nonusers.

The researchers found this risk reduction was significant in subgroups of patients with diabetes, liver cirrhosis, and those on antiviral therapy, and they suggested that the antiangiogenic, immunomodulatory, antiproliferative, and antifibrotic properties of statins may contribute to their potential to reduce tumor growth or hepatocellular carcinoma development.

The meta-analysis authors noted that although most studies have reported a low risk for statin-induced hepatotoxicity, clinicians should proceed with caution in some patients with existing cirrhosis.

“If the patients are diagnosed with decompensated cirrhosis, then statins should be prescribed with caution at low doses,” they wrote.

Advocating statin use solely for chemoprevention may be premature based on observational data, Chung told GI & Hepatology News.

“However, in patients with [chronic liver disease] who already meet indications for statin therapy, the potential added benefit of reducing liver-related complications strengthens the rationale for their use,” he said. Future randomized clinical trials will be key to defining the risk-benefit profile in this context.

The study by Choi and colleagues was supported by the National Institutes of Health.

The study by Sharma and colleagues was supported by the Karolinska Institutet, Stockholm, Sweden, and the Columbia University Irving Medical Center, New York City; researchers were supported by grants from the Swedish Research Council, Center for Innovative Medicine, the Swedish Cancer Society, and the National Institutes of Health.

The study by Vell and colleagues had no outside funding.

The study by Mohaimenul Islam and colleagues was supported by the Ministry of Education and Ministry of Science and Technology, Taiwan.

Chung and Banini had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Long-term use of statins may delay or deflect the development of hepatocellular carcinoma in adults with chronic liver disease, as well as in the general population, emerging research, including several large cohort studies, suggested.

The most recent study, published in JAMA Internal Medicine, showed a lower incidence of hepatic decompensation among statin users in a registry for adults aged 40 years or older with baseline chronic liver disease.

“Our findings support the idea that statins may offer benefits beyond lipid-lowering in patients with [chronic liver disease], and clinicians may be more confident in prescribing statins when indicated,” even in these patients, said corresponding Co-author Raymond T. Chung, MD, gastroenterology investigator at Mass General Research Institute, Boston, in an interview. 

“While prior studies have suggested an association between statin use and reduced hepatocellular carcinoma risk, our study aimed to build on that evidence by using a large, real-world, hospital-based cohort inclusive of all etiologies of chronic liver disease,” Chung told GI & Hepatology News.

Chung, along with Jonggi Choi, MD, of the University of Ulsan College of Medicine, Seoul, South Korea, and colleagues, reviewed data from the Research Patient Data Registry from 2000 to 2023 for 16,501 participantsaged 40 years or older with baseline chronic liver disease and baseline Fibrosis-4 (FIB-4) scores ≥ 1.3.

The study population had a mean age of 59.7 years, and 40.9% were women. The researchers divided the population into statin users (n = 3610) and nonusers (n = 12,891). Statin use was defined as a cumulative defined daily dose ≥ 30 mg.

The primary outcome was the cumulative incidence of hepatocellular carcinoma and hepatic decompensation.

At 10 years follow-up, statin users showed a significantly reduced incidence of hepatocellular carcinoma vs nonusers (3.8% vs 8.0%; P < .001) as well as a significantly reduced incidence of hepatic decompensation (10.6% vs 19.5%; P < .001).

Incorporating FIB-4 scores, a surrogate marker for liver fibrosis, also showed that statin users were less likely to experience fibrosis progression, offering a potential mechanism of action for the observed reduction in adverse liver outcomes, Chung told GI & Hepatology News.

“Similar trends have been observed in prior observational studies, but our findings now support a real effect of statin use on fibrosis progression,” he said. “However, what strengthened our study was that the association remained consistent across multiple subgroups and sensitivity analyses.”

Another study published in Clinical Gastroenterology and Hepatology showed a reduced risk of developing severe liver disease in a Swedish cohort of noncirrhotic adults with chronic liver disease who used statins (n = 3862) compared with control patients with chronic liver disease (matched 1:1) and who did not use statins (hazard ratio [HR], 0.60). 

In that study, Rajani Sharma, MD, and colleagues found a protective association in both prefibrosis and fibrosis stages at diagnosis, and statin use was associated with reduced rates of progression to both cirrhosis and hepatocellular carcinoma (HR, 0.62 and 0.44, respectively).

 

Exciting and Necessary Research

The research by Choi and colleagues is “exciting,” said Bubu Banini, MD, PhD, an assistant professor in digestive diseases at Yale School of Medicine, New Haven, Connecticut, in an interview.

Liver cancer prevalence has risen over the past few decades in the United States and worldwide, and the 5-year overall survival rate of liver cancer is less than 20%, Banini told GI & Hepatology News.

Clinicians often withhold statins out of fear of liver injury in persons with chronic liver disease; however, a takeaway from this study is that for persons with chronic liver disease who have indications for statin use, the medication should not be withheld, she said.

Of course, prospective studies are needed to replicate the results, Banini added.

The study findings were limited by several factors, including the inability to adjust for all potential confounding variables, lack of data on post-index treatments, and the use of wide, cumulative, defined daily dose categories to ensure statistical power, the researchers noted.

“Moving forward, randomized controlled trials are essential to establish a causal relationship and clarify the molecular and clinical pathways through which statins exert hepatoprotective effects,” Chung added.

Randomized controlled trials are also needed to determine whether statins can actually reduce the risk for hepatocellular carcinoma and hepatic decompensation in patients with chronic liver disease, and cost-effectiveness analyses may be essential for translating this evidence into clinical guidelines, he added.

 

Statins and HCC Risk in the General Population

A large cohort study, published in JAMA Network Open by Mara Sophie Vell, PhD, and colleagues, showed an association between reduced risk for hepatocellular carcinoma and statin use in the general population and in those at increased risk for liver disease.

The study, which included data for individuals aged 37-73 years from the UK Biobank, found a 15% reduced risk for new-onset liver disease and a 28% reduced risk for liver-related death among regular statin users than among nonusers (HR, 0.85 and 0.72, respectively). 

In addition, regular statin users showed a 74% reduced risk (P = .003) of developing hepatocellular carcinoma compared with those not using statins. The researchers identified a particular impact on liver disease risk reduction among men, individuals with diabetes, and patients with high levels of liver scarring at baseline based on the FIB-4 index.

A meta-analysis of 24 studies, previously published in the journal Cancers, showed a significant reduction of 46% in hepatocellular carcinoma risk among statins users compared with nonusers.

The researchers found this risk reduction was significant in subgroups of patients with diabetes, liver cirrhosis, and those on antiviral therapy, and they suggested that the antiangiogenic, immunomodulatory, antiproliferative, and antifibrotic properties of statins may contribute to their potential to reduce tumor growth or hepatocellular carcinoma development.

The meta-analysis authors noted that although most studies have reported a low risk for statin-induced hepatotoxicity, clinicians should proceed with caution in some patients with existing cirrhosis.

“If the patients are diagnosed with decompensated cirrhosis, then statins should be prescribed with caution at low doses,” they wrote.

Advocating statin use solely for chemoprevention may be premature based on observational data, Chung told GI & Hepatology News.

“However, in patients with [chronic liver disease] who already meet indications for statin therapy, the potential added benefit of reducing liver-related complications strengthens the rationale for their use,” he said. Future randomized clinical trials will be key to defining the risk-benefit profile in this context.

The study by Choi and colleagues was supported by the National Institutes of Health.

The study by Sharma and colleagues was supported by the Karolinska Institutet, Stockholm, Sweden, and the Columbia University Irving Medical Center, New York City; researchers were supported by grants from the Swedish Research Council, Center for Innovative Medicine, the Swedish Cancer Society, and the National Institutes of Health.

The study by Vell and colleagues had no outside funding.

The study by Mohaimenul Islam and colleagues was supported by the Ministry of Education and Ministry of Science and Technology, Taiwan.

Chung and Banini had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

A recent study supports the importance of intensive nutrition therapy in managing patients with alcohol-related acute-on-chronic liver failure (ACLF).

In a randomized controlled trial, compared with standard care, dietitian-supported, intensive nutritional therapy improved survival, reduced frailty, and lowered hospitalization rates in men with alcohol-related ACLF.

The study, performed by a team from the Postgraduate Institute of Medical Education and Research, Chandigarh, India, was published in Clinical Gastroenterology and Hepatology.

ACLF related to alcohol use is associated with poor outcomes due to poor nutritional intake and frailty. Frail patients with ACLF face higher morbidity, mortality, and hospitalization rates than their nonfrail counterparts. However, research on the role of structured nutritional interventions in improving these outcomes is limited.

Patal Giri, MBBS, MD, and colleagues enrolled 70 men with alcohol-related ACLF and frailty (liver frailty index [LFI] > 4.5) in a single-center, open-label study. Half were randomly allocated to an intervention group receiving outpatient intensive nutrition therapy (OINT) plus standard medical treatment (SMT) and half to a control group receiving SMT alone for 3 months.

The intervention group received a monitored high-calorie, high-protein, and salt-restricted diet as prescribed by a dedicated senior liver dietitian. The control group received regular nutritional recommendations and were managed for the ACLF-associated complications, without intervention or guidance by the study team.

After 3 months follow-up, overall survival (the primary outcome) was significantly improved in the OINT group compared with the control group (91.4% vs 57.1%), “suggesting that the improvement in nutrition status is associated with better survival,” the study team noted. Three patients died in the OINT group vs 15 in the SMT group.

OINT also led to a significant improvement in frailty, with LFI scores decreasing by an average of 0.93 in the intervention group vs 0.33 in the control group; 97% of patients improved from frail to prefrail status in the OINT group, whereas only 20% of patients improved in the SMT group.

The mean change in LFI of 0.93 with OINT is “well above the substantially clinically important difference” (change of 0.8) established in a previous study, the authors noted.

Significant improvements in weight and body mass index were also observed in the OINT group relative to the control group.

Liver disease severity, including model for end-stage liver disease (MELD) scores, showed greater improvement in the OINT group than in the control group (−8.7 vs −6.3 points from baseline to 3 months).

During the follow-up period, fewer patients in the intervention group than in the control group required a hospital stay (17% vs 45.7%).

Limitations of the study include the single-center design and the short follow-up period of 3 months, which limits long-term outcome assessment. Further, the study only included patients meeting Asia Pacific Association for Study of Liver criteria for ACLF, which does not include the patients with organ failure as defined by European Association for the Study of the Liver-Chronic Liver Failure Consortium criteria. Patients with ACLF who had more severe disease (MELD score > 30 or AARC > 10) were also not included.

Despite these limitations, the authors said their study showed that “dietician-monitored goal-directed nutrition therapy is very important in the management of patients with alcohol-related ACLF along with SMT.”

 

Confirmatory Data 

Reached for comment, Katherine Patton, MEd, RD, a registered dietitian with the Center for Human Nutrition at Cleveland Clinic, Cleveland, Ohio, said it’s well known that the ACLF patient population has a “very high rate of morbidity and mortality and their quality of life tends to be poor due to their frailty. It is also fairly well-known that proper nutrition therapy can improve outcomes, however barriers to adequate nutrition include decreased appetite, nausea, pain, altered taste, and early satiety from ascites.”

“Hepatologists are likely stressing the importance of adequate protein energy intake and doctors may refer patients to an outpatient dietitian, but it is up to the patient to make that appointment and act on the recommendations,” Patton told GI & Hepatology News.

“If a dietitian works in the same clinic as the hepatologist and patients can be referred and seen the same day, this is ideal. During a hospital admission, protein/calorie intake can be more closely monitored and encouraged by a multi-disciplinary team,” Patton explained.

She cautioned that “the average patient is not familiar with how to apply general calorie and protein goals to their everyday eating habits. This study amplifies the role of a dietitian and what consistent education and resources can do to improve a patient’s quality of life and survival.”

This study had no specific funding. The authors have declared no relevant conflicts of interest. Patton had no relevant disclosures.

A version of this article appeared on Medscape.com.

A recent study supports the importance of intensive nutrition therapy in managing patients with alcohol-related acute-on-chronic liver failure (ACLF).

In a randomized controlled trial, compared with standard care, dietitian-supported, intensive nutritional therapy improved survival, reduced frailty, and lowered hospitalization rates in men with alcohol-related ACLF.

The study, performed by a team from the Postgraduate Institute of Medical Education and Research, Chandigarh, India, was published in Clinical Gastroenterology and Hepatology.

ACLF related to alcohol use is associated with poor outcomes due to poor nutritional intake and frailty. Frail patients with ACLF face higher morbidity, mortality, and hospitalization rates than their nonfrail counterparts. However, research on the role of structured nutritional interventions in improving these outcomes is limited.

Patal Giri, MBBS, MD, and colleagues enrolled 70 men with alcohol-related ACLF and frailty (liver frailty index [LFI] > 4.5) in a single-center, open-label study. Half were randomly allocated to an intervention group receiving outpatient intensive nutrition therapy (OINT) plus standard medical treatment (SMT) and half to a control group receiving SMT alone for 3 months.

The intervention group received a monitored high-calorie, high-protein, and salt-restricted diet as prescribed by a dedicated senior liver dietitian. The control group received regular nutritional recommendations and were managed for the ACLF-associated complications, without intervention or guidance by the study team.

After 3 months follow-up, overall survival (the primary outcome) was significantly improved in the OINT group compared with the control group (91.4% vs 57.1%), “suggesting that the improvement in nutrition status is associated with better survival,” the study team noted. Three patients died in the OINT group vs 15 in the SMT group.

OINT also led to a significant improvement in frailty, with LFI scores decreasing by an average of 0.93 in the intervention group vs 0.33 in the control group; 97% of patients improved from frail to prefrail status in the OINT group, whereas only 20% of patients improved in the SMT group.

The mean change in LFI of 0.93 with OINT is “well above the substantially clinically important difference” (change of 0.8) established in a previous study, the authors noted.

Significant improvements in weight and body mass index were also observed in the OINT group relative to the control group.

Liver disease severity, including model for end-stage liver disease (MELD) scores, showed greater improvement in the OINT group than in the control group (−8.7 vs −6.3 points from baseline to 3 months).

During the follow-up period, fewer patients in the intervention group than in the control group required a hospital stay (17% vs 45.7%).

Limitations of the study include the single-center design and the short follow-up period of 3 months, which limits long-term outcome assessment. Further, the study only included patients meeting Asia Pacific Association for Study of Liver criteria for ACLF, which does not include the patients with organ failure as defined by European Association for the Study of the Liver-Chronic Liver Failure Consortium criteria. Patients with ACLF who had more severe disease (MELD score > 30 or AARC > 10) were also not included.

Despite these limitations, the authors said their study showed that “dietician-monitored goal-directed nutrition therapy is very important in the management of patients with alcohol-related ACLF along with SMT.”

 

Confirmatory Data 

Reached for comment, Katherine Patton, MEd, RD, a registered dietitian with the Center for Human Nutrition at Cleveland Clinic, Cleveland, Ohio, said it’s well known that the ACLF patient population has a “very high rate of morbidity and mortality and their quality of life tends to be poor due to their frailty. It is also fairly well-known that proper nutrition therapy can improve outcomes, however barriers to adequate nutrition include decreased appetite, nausea, pain, altered taste, and early satiety from ascites.”

“Hepatologists are likely stressing the importance of adequate protein energy intake and doctors may refer patients to an outpatient dietitian, but it is up to the patient to make that appointment and act on the recommendations,” Patton told GI & Hepatology News.

“If a dietitian works in the same clinic as the hepatologist and patients can be referred and seen the same day, this is ideal. During a hospital admission, protein/calorie intake can be more closely monitored and encouraged by a multi-disciplinary team,” Patton explained.

She cautioned that “the average patient is not familiar with how to apply general calorie and protein goals to their everyday eating habits. This study amplifies the role of a dietitian and what consistent education and resources can do to improve a patient’s quality of life and survival.”

This study had no specific funding. The authors have declared no relevant conflicts of interest. Patton had no relevant disclosures.

A version of this article appeared on Medscape.com.

A recent study supports the importance of intensive nutrition therapy in managing patients with alcohol-related acute-on-chronic liver failure (ACLF).

In a randomized controlled trial, compared with standard care, dietitian-supported, intensive nutritional therapy improved survival, reduced frailty, and lowered hospitalization rates in men with alcohol-related ACLF.

The study, performed by a team from the Postgraduate Institute of Medical Education and Research, Chandigarh, India, was published in Clinical Gastroenterology and Hepatology.

ACLF related to alcohol use is associated with poor outcomes due to poor nutritional intake and frailty. Frail patients with ACLF face higher morbidity, mortality, and hospitalization rates than their nonfrail counterparts. However, research on the role of structured nutritional interventions in improving these outcomes is limited.

Patal Giri, MBBS, MD, and colleagues enrolled 70 men with alcohol-related ACLF and frailty (liver frailty index [LFI] > 4.5) in a single-center, open-label study. Half were randomly allocated to an intervention group receiving outpatient intensive nutrition therapy (OINT) plus standard medical treatment (SMT) and half to a control group receiving SMT alone for 3 months.

The intervention group received a monitored high-calorie, high-protein, and salt-restricted diet as prescribed by a dedicated senior liver dietitian. The control group received regular nutritional recommendations and were managed for the ACLF-associated complications, without intervention or guidance by the study team.

After 3 months follow-up, overall survival (the primary outcome) was significantly improved in the OINT group compared with the control group (91.4% vs 57.1%), “suggesting that the improvement in nutrition status is associated with better survival,” the study team noted. Three patients died in the OINT group vs 15 in the SMT group.

OINT also led to a significant improvement in frailty, with LFI scores decreasing by an average of 0.93 in the intervention group vs 0.33 in the control group; 97% of patients improved from frail to prefrail status in the OINT group, whereas only 20% of patients improved in the SMT group.

The mean change in LFI of 0.93 with OINT is “well above the substantially clinically important difference” (change of 0.8) established in a previous study, the authors noted.

Significant improvements in weight and body mass index were also observed in the OINT group relative to the control group.

Liver disease severity, including model for end-stage liver disease (MELD) scores, showed greater improvement in the OINT group than in the control group (−8.7 vs −6.3 points from baseline to 3 months).

During the follow-up period, fewer patients in the intervention group than in the control group required a hospital stay (17% vs 45.7%).

Limitations of the study include the single-center design and the short follow-up period of 3 months, which limits long-term outcome assessment. Further, the study only included patients meeting Asia Pacific Association for Study of Liver criteria for ACLF, which does not include the patients with organ failure as defined by European Association for the Study of the Liver-Chronic Liver Failure Consortium criteria. Patients with ACLF who had more severe disease (MELD score > 30 or AARC > 10) were also not included.

Despite these limitations, the authors said their study showed that “dietician-monitored goal-directed nutrition therapy is very important in the management of patients with alcohol-related ACLF along with SMT.”

 

Confirmatory Data 

Reached for comment, Katherine Patton, MEd, RD, a registered dietitian with the Center for Human Nutrition at Cleveland Clinic, Cleveland, Ohio, said it’s well known that the ACLF patient population has a “very high rate of morbidity and mortality and their quality of life tends to be poor due to their frailty. It is also fairly well-known that proper nutrition therapy can improve outcomes, however barriers to adequate nutrition include decreased appetite, nausea, pain, altered taste, and early satiety from ascites.”

“Hepatologists are likely stressing the importance of adequate protein energy intake and doctors may refer patients to an outpatient dietitian, but it is up to the patient to make that appointment and act on the recommendations,” Patton told GI & Hepatology News.

“If a dietitian works in the same clinic as the hepatologist and patients can be referred and seen the same day, this is ideal. During a hospital admission, protein/calorie intake can be more closely monitored and encouraged by a multi-disciplinary team,” Patton explained.

She cautioned that “the average patient is not familiar with how to apply general calorie and protein goals to their everyday eating habits. This study amplifies the role of a dietitian and what consistent education and resources can do to improve a patient’s quality of life and survival.”

This study had no specific funding. The authors have declared no relevant conflicts of interest. Patton had no relevant disclosures.

A version of this article appeared on Medscape.com.

New research highlights the promise of artificial intelligence (AI) for opportunistic screening of chronic liver disease (CLD) through routine echocardiography. 

An AI algorithm called EchoNet-Liver demonstrated strong performance for detecting cirrhosis and steatotic liver disease (SLD) from routinely acquired transthoracic echocardiography studies containing subcostal images of the liver, the developers reported in NEJM AI.

“We hope that this algorithm enables physicians to opportunistically screen for chronic liver disease to identify asymptomatic and undiagnosed patients, thus enabling us to treat comorbidities relevant to the patient’s cardiovascular and noncardiovascular health,” Alan C. Kwan, MD, assistant professor, Department of Cardiology, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told this news organization.

 

Harnessing Echo to Reveal Liver Trouble 

CLD affects over 1.5 billion people globally, with many cases remaining undiagnosed due to the asymptomatic nature of early disease and a lack of routine screening. Traditional diagnostic methods such as liver function tests, ultrasonography, and MRI are often limited by cost, availability, and patient access.

Echocardiography is a commonly performed imaging study that incidentally captures images of the liver but is not utilized for liver disease assessment.

EchoNet-Liver is an AI algorithm that can identify high-quality subcostal images from full echocardiography studies and detect the presence of cirrhosis and SLD. 

Kwan and colleagues trained it using nearly 1.6 million echocardiogram videos from 66,922 studies and 24,276 adult patients at Cedars-Sinai Medical Center (CSMC). The model predictions were compared with diagnoses from clinical evaluations of paired abdominal ultrasound or MRI studies. External validation studies were conducted using similar data from Stanford Health Care. 

In the “held-out” CSMC ultrasound dataset, EchoNet-Liver detected cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.837 (95% CI, 0.828-0.848) and SLD with an AUROC of 0.799 (95% CI, 0.788-0.811).

The algorithm showed a sensitivity of 69.6% and a specificity of 84.6% for detecting cirrhosis, and a sensitivity of 74.1% and a specificity of 72.0% for detecting SLD. 

In the Stanford Health Care external-validation test ultrasound cohort, the model detected cirrhosis with an AUROC of 0.830 (95% CI, 0.799-0.859) and SLD with an AUROC of 0.769 (95% CI, 0.733-0.813), with sensitivity and specificity of 80.0% and 70.9%, respectively, for cirrhosis and 66.7% and 78.0%, respectively, for SLD. 

In the CSMC MRI-paired cohort, EchoNet-Liver detected cirrhosis with an AUROC of 0.704 (95% CI, 0.699-0.708) and SLD with an AUROC of 0.725 (95% CI, 0.707-0.762).

 

Identifying Subclinical Liver Disease to Improve Outcomes

“Across diverse populations and disease definitions, deep-learning-enhanced echocardiography enabled high-throughput, automated detection of CLD, which could enable opportunistic screening for asymptomatic liver disease,” the authors wrote. 

“By improving the diagnosis of subclinical CLD, we may be able to limit or reverse disease progression and improve care by triaging patients toward appropriate clinical and diagnostic management,” they said. 

By way of limitations, the researchers noted that the tool was developed using a cohort of patients who had both abdominal ultrasound and echocardiography within 30 days, and thus probably had a higher prevalence of liver disease compared with the general population receiving echocardiography. The true clinical utility of EchoNet-Liver will depend on whether its application to a general echocardiography population can efficiently detect undiagnosed CLD, they cautioned. 

“While we developed this algorithm based on clinical data, the application within the clinic would typically require FDA approval, which we have not yet applied for,” Kwan told this news organization.

“We plan to prospectively validate this algorithm at multiple sites to ensure that application of this algorithm improves patient care without causing excess diagnostic testing, thus providing value to patients and the healthcare system as a whole,” Kwan said.

Funding was provided in part by KAKENHI (Japan Society for the Promotion of Science). Kwan reported receiving consulting fees from InVision.

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

New research highlights the promise of artificial intelligence (AI) for opportunistic screening of chronic liver disease (CLD) through routine echocardiography. 

An AI algorithm called EchoNet-Liver demonstrated strong performance for detecting cirrhosis and steatotic liver disease (SLD) from routinely acquired transthoracic echocardiography studies containing subcostal images of the liver, the developers reported in NEJM AI.

“We hope that this algorithm enables physicians to opportunistically screen for chronic liver disease to identify asymptomatic and undiagnosed patients, thus enabling us to treat comorbidities relevant to the patient’s cardiovascular and noncardiovascular health,” Alan C. Kwan, MD, assistant professor, Department of Cardiology, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told this news organization.

 

Harnessing Echo to Reveal Liver Trouble 

CLD affects over 1.5 billion people globally, with many cases remaining undiagnosed due to the asymptomatic nature of early disease and a lack of routine screening. Traditional diagnostic methods such as liver function tests, ultrasonography, and MRI are often limited by cost, availability, and patient access.

Echocardiography is a commonly performed imaging study that incidentally captures images of the liver but is not utilized for liver disease assessment.

EchoNet-Liver is an AI algorithm that can identify high-quality subcostal images from full echocardiography studies and detect the presence of cirrhosis and SLD. 

Kwan and colleagues trained it using nearly 1.6 million echocardiogram videos from 66,922 studies and 24,276 adult patients at Cedars-Sinai Medical Center (CSMC). The model predictions were compared with diagnoses from clinical evaluations of paired abdominal ultrasound or MRI studies. External validation studies were conducted using similar data from Stanford Health Care. 

In the “held-out” CSMC ultrasound dataset, EchoNet-Liver detected cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.837 (95% CI, 0.828-0.848) and SLD with an AUROC of 0.799 (95% CI, 0.788-0.811).

The algorithm showed a sensitivity of 69.6% and a specificity of 84.6% for detecting cirrhosis, and a sensitivity of 74.1% and a specificity of 72.0% for detecting SLD. 

In the Stanford Health Care external-validation test ultrasound cohort, the model detected cirrhosis with an AUROC of 0.830 (95% CI, 0.799-0.859) and SLD with an AUROC of 0.769 (95% CI, 0.733-0.813), with sensitivity and specificity of 80.0% and 70.9%, respectively, for cirrhosis and 66.7% and 78.0%, respectively, for SLD. 

In the CSMC MRI-paired cohort, EchoNet-Liver detected cirrhosis with an AUROC of 0.704 (95% CI, 0.699-0.708) and SLD with an AUROC of 0.725 (95% CI, 0.707-0.762).

 

Identifying Subclinical Liver Disease to Improve Outcomes

“Across diverse populations and disease definitions, deep-learning-enhanced echocardiography enabled high-throughput, automated detection of CLD, which could enable opportunistic screening for asymptomatic liver disease,” the authors wrote. 

“By improving the diagnosis of subclinical CLD, we may be able to limit or reverse disease progression and improve care by triaging patients toward appropriate clinical and diagnostic management,” they said. 

By way of limitations, the researchers noted that the tool was developed using a cohort of patients who had both abdominal ultrasound and echocardiography within 30 days, and thus probably had a higher prevalence of liver disease compared with the general population receiving echocardiography. The true clinical utility of EchoNet-Liver will depend on whether its application to a general echocardiography population can efficiently detect undiagnosed CLD, they cautioned. 

“While we developed this algorithm based on clinical data, the application within the clinic would typically require FDA approval, which we have not yet applied for,” Kwan told this news organization.

“We plan to prospectively validate this algorithm at multiple sites to ensure that application of this algorithm improves patient care without causing excess diagnostic testing, thus providing value to patients and the healthcare system as a whole,” Kwan said.

Funding was provided in part by KAKENHI (Japan Society for the Promotion of Science). Kwan reported receiving consulting fees from InVision.

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

New research highlights the promise of artificial intelligence (AI) for opportunistic screening of chronic liver disease (CLD) through routine echocardiography. 

An AI algorithm called EchoNet-Liver demonstrated strong performance for detecting cirrhosis and steatotic liver disease (SLD) from routinely acquired transthoracic echocardiography studies containing subcostal images of the liver, the developers reported in NEJM AI.

“We hope that this algorithm enables physicians to opportunistically screen for chronic liver disease to identify asymptomatic and undiagnosed patients, thus enabling us to treat comorbidities relevant to the patient’s cardiovascular and noncardiovascular health,” Alan C. Kwan, MD, assistant professor, Department of Cardiology, Smidt Heart Institute at Cedars-Sinai, Los Angeles, California, told this news organization.

 

Harnessing Echo to Reveal Liver Trouble 

CLD affects over 1.5 billion people globally, with many cases remaining undiagnosed due to the asymptomatic nature of early disease and a lack of routine screening. Traditional diagnostic methods such as liver function tests, ultrasonography, and MRI are often limited by cost, availability, and patient access.

Echocardiography is a commonly performed imaging study that incidentally captures images of the liver but is not utilized for liver disease assessment.

EchoNet-Liver is an AI algorithm that can identify high-quality subcostal images from full echocardiography studies and detect the presence of cirrhosis and SLD. 

Kwan and colleagues trained it using nearly 1.6 million echocardiogram videos from 66,922 studies and 24,276 adult patients at Cedars-Sinai Medical Center (CSMC). The model predictions were compared with diagnoses from clinical evaluations of paired abdominal ultrasound or MRI studies. External validation studies were conducted using similar data from Stanford Health Care. 

In the “held-out” CSMC ultrasound dataset, EchoNet-Liver detected cirrhosis with an area under the receiver operating characteristic curve (AUROC) of 0.837 (95% CI, 0.828-0.848) and SLD with an AUROC of 0.799 (95% CI, 0.788-0.811).

The algorithm showed a sensitivity of 69.6% and a specificity of 84.6% for detecting cirrhosis, and a sensitivity of 74.1% and a specificity of 72.0% for detecting SLD. 

In the Stanford Health Care external-validation test ultrasound cohort, the model detected cirrhosis with an AUROC of 0.830 (95% CI, 0.799-0.859) and SLD with an AUROC of 0.769 (95% CI, 0.733-0.813), with sensitivity and specificity of 80.0% and 70.9%, respectively, for cirrhosis and 66.7% and 78.0%, respectively, for SLD. 

In the CSMC MRI-paired cohort, EchoNet-Liver detected cirrhosis with an AUROC of 0.704 (95% CI, 0.699-0.708) and SLD with an AUROC of 0.725 (95% CI, 0.707-0.762).

 

Identifying Subclinical Liver Disease to Improve Outcomes

“Across diverse populations and disease definitions, deep-learning-enhanced echocardiography enabled high-throughput, automated detection of CLD, which could enable opportunistic screening for asymptomatic liver disease,” the authors wrote. 

“By improving the diagnosis of subclinical CLD, we may be able to limit or reverse disease progression and improve care by triaging patients toward appropriate clinical and diagnostic management,” they said. 

By way of limitations, the researchers noted that the tool was developed using a cohort of patients who had both abdominal ultrasound and echocardiography within 30 days, and thus probably had a higher prevalence of liver disease compared with the general population receiving echocardiography. The true clinical utility of EchoNet-Liver will depend on whether its application to a general echocardiography population can efficiently detect undiagnosed CLD, they cautioned. 

“While we developed this algorithm based on clinical data, the application within the clinic would typically require FDA approval, which we have not yet applied for,” Kwan told this news organization.

“We plan to prospectively validate this algorithm at multiple sites to ensure that application of this algorithm improves patient care without causing excess diagnostic testing, thus providing value to patients and the healthcare system as a whole,” Kwan said.

Funding was provided in part by KAKENHI (Japan Society for the Promotion of Science). Kwan reported receiving consulting fees from InVision.

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

Despite universal hepatitis C virus (HCV) screening recommendations issued in 2020, HCV screening rates remain suboptimal among US women, a new analysis showed. 

“We found that screening rates were higher and rose more steeply in pregnant individuals compared to nonpregnant reproductive age females after this guidance.” However overall, HCV screening in women still remained low by the end of 2022, authors Roshni Singh, MD, and Rachel Epstein, MD, MSc, with the section of infectious diseases, Boston Medical Center, noted in an email to this news organization.

The study was published online in JAMA.

The researchers leveraged TriNetX LIVE electronic health record data to compare HCV screening rates from 68 US healthcare organizations covering more than 115 million patients.

Using a multiple-group interrupted time series analysis, they compared HCV screening rates for pregnant and nonpregnant women for each 6-month period before (January 2014 to December 2019) and after (July 2020 to December 2022) the 2020 guidelines. January to June 2020 was considered a washout period to account for the COVID-19 pandemic peak and guideline dissemination.

For the entire 9-year study period (2014-2022), a total of 79,231 incident HCV tests occurred among pregnant women and 678,951 occurred among nonpregnant women. 

In the 6 months before the guidance, HCV screening per 1000 person-years increased from 52 to 117 tests among pregnant women and 16 to 24 tests among nonpregnant women.

In the 6 months after the guidance, screening per 1000 person-years increased from 141 to 253 among pregnant women and from 29 to 37 among nonpregnant women.

Yet by the end of 2022, only 38.7% of women with a pregnancy and 8.7% of nonpregnant women were ever tested for the HCV.

 

How to Boost HCV Screening

These results suggest that “innovative strategies are needed to improve HCV diagnosis and treatment,” the authors wrote. 

“Several interventions have been demonstrated to be effective in increasing screening in general, including electronic medical record alerts for opt-out testing, routine test offer by nonclinician office staff, offering testing in nontraditional spaces, including substance use treatment programs, harm reduction centers, STI clinics, and mobile health units,” Singh and Epstein told this news organization.

“A key step is educating primary care providers in addition to addiction medicine and emergency medicine clinicians about the updated guidelines as they interface with a large number of at-risk individuals,” they said. And the most important measure is creating clear work flows that respond to positive results to link people to treatment and cure. 

“Clinicians need to feel empowered that their work screening a patient can make a meaningful difference in both the patient’s life and in helping end this epidemic,” the two researchers explained. 

Aaron Glatt, MD, a spokesperson for the Infectious Diseases Society of America, who wasn’t involved in the study, told this news organization that the low HCV screening rates are not surprising. 

“We tend not to do well with screening. It’s not necessarily anybody’s fault, but patients don’t necessarily want to be screened. Sometimes physicians are very busy. Sometimes screening is not the most important thing for them to do. Sometimes there are processes in place that fall through,” said Glatt, chief of infectious diseases and hospital epidemiologist at Mount Sinai South Nassau, Oceanside, New York. 

“We tend to do a better job of screening in pregnant than nonpregnant women because pregnancy is a focus and there is 9 months that you can be following-up, so there is more opportunity. A healthy nonpregnant woman may not see her doctor for another year,” Glatt noted. 

“I think that many physicians are very good at screening for hepatitis C in patients that are clearly at risk,” he added. “We’re not so good at screening for people” that don’t have a clear risk but do “have risk factors.”

The study had no commercial funding. Singh, Epstein, and Glatt had no relevant disclosures.

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

Despite universal hepatitis C virus (HCV) screening recommendations issued in 2020, HCV screening rates remain suboptimal among US women, a new analysis showed. 

“We found that screening rates were higher and rose more steeply in pregnant individuals compared to nonpregnant reproductive age females after this guidance.” However overall, HCV screening in women still remained low by the end of 2022, authors Roshni Singh, MD, and Rachel Epstein, MD, MSc, with the section of infectious diseases, Boston Medical Center, noted in an email to this news organization.

The study was published online in JAMA.

The researchers leveraged TriNetX LIVE electronic health record data to compare HCV screening rates from 68 US healthcare organizations covering more than 115 million patients.

Using a multiple-group interrupted time series analysis, they compared HCV screening rates for pregnant and nonpregnant women for each 6-month period before (January 2014 to December 2019) and after (July 2020 to December 2022) the 2020 guidelines. January to June 2020 was considered a washout period to account for the COVID-19 pandemic peak and guideline dissemination.

For the entire 9-year study period (2014-2022), a total of 79,231 incident HCV tests occurred among pregnant women and 678,951 occurred among nonpregnant women. 

In the 6 months before the guidance, HCV screening per 1000 person-years increased from 52 to 117 tests among pregnant women and 16 to 24 tests among nonpregnant women.

In the 6 months after the guidance, screening per 1000 person-years increased from 141 to 253 among pregnant women and from 29 to 37 among nonpregnant women.

Yet by the end of 2022, only 38.7% of women with a pregnancy and 8.7% of nonpregnant women were ever tested for the HCV.

 

How to Boost HCV Screening

These results suggest that “innovative strategies are needed to improve HCV diagnosis and treatment,” the authors wrote. 

“Several interventions have been demonstrated to be effective in increasing screening in general, including electronic medical record alerts for opt-out testing, routine test offer by nonclinician office staff, offering testing in nontraditional spaces, including substance use treatment programs, harm reduction centers, STI clinics, and mobile health units,” Singh and Epstein told this news organization.

“A key step is educating primary care providers in addition to addiction medicine and emergency medicine clinicians about the updated guidelines as they interface with a large number of at-risk individuals,” they said. And the most important measure is creating clear work flows that respond to positive results to link people to treatment and cure. 

“Clinicians need to feel empowered that their work screening a patient can make a meaningful difference in both the patient’s life and in helping end this epidemic,” the two researchers explained. 

Aaron Glatt, MD, a spokesperson for the Infectious Diseases Society of America, who wasn’t involved in the study, told this news organization that the low HCV screening rates are not surprising. 

“We tend not to do well with screening. It’s not necessarily anybody’s fault, but patients don’t necessarily want to be screened. Sometimes physicians are very busy. Sometimes screening is not the most important thing for them to do. Sometimes there are processes in place that fall through,” said Glatt, chief of infectious diseases and hospital epidemiologist at Mount Sinai South Nassau, Oceanside, New York. 

“We tend to do a better job of screening in pregnant than nonpregnant women because pregnancy is a focus and there is 9 months that you can be following-up, so there is more opportunity. A healthy nonpregnant woman may not see her doctor for another year,” Glatt noted. 

“I think that many physicians are very good at screening for hepatitis C in patients that are clearly at risk,” he added. “We’re not so good at screening for people” that don’t have a clear risk but do “have risk factors.”

The study had no commercial funding. Singh, Epstein, and Glatt had no relevant disclosures.

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

Despite universal hepatitis C virus (HCV) screening recommendations issued in 2020, HCV screening rates remain suboptimal among US women, a new analysis showed. 

“We found that screening rates were higher and rose more steeply in pregnant individuals compared to nonpregnant reproductive age females after this guidance.” However overall, HCV screening in women still remained low by the end of 2022, authors Roshni Singh, MD, and Rachel Epstein, MD, MSc, with the section of infectious diseases, Boston Medical Center, noted in an email to this news organization.

The study was published online in JAMA.

The researchers leveraged TriNetX LIVE electronic health record data to compare HCV screening rates from 68 US healthcare organizations covering more than 115 million patients.

Using a multiple-group interrupted time series analysis, they compared HCV screening rates for pregnant and nonpregnant women for each 6-month period before (January 2014 to December 2019) and after (July 2020 to December 2022) the 2020 guidelines. January to June 2020 was considered a washout period to account for the COVID-19 pandemic peak and guideline dissemination.

For the entire 9-year study period (2014-2022), a total of 79,231 incident HCV tests occurred among pregnant women and 678,951 occurred among nonpregnant women. 

In the 6 months before the guidance, HCV screening per 1000 person-years increased from 52 to 117 tests among pregnant women and 16 to 24 tests among nonpregnant women.

In the 6 months after the guidance, screening per 1000 person-years increased from 141 to 253 among pregnant women and from 29 to 37 among nonpregnant women.

Yet by the end of 2022, only 38.7% of women with a pregnancy and 8.7% of nonpregnant women were ever tested for the HCV.

 

How to Boost HCV Screening

These results suggest that “innovative strategies are needed to improve HCV diagnosis and treatment,” the authors wrote. 

“Several interventions have been demonstrated to be effective in increasing screening in general, including electronic medical record alerts for opt-out testing, routine test offer by nonclinician office staff, offering testing in nontraditional spaces, including substance use treatment programs, harm reduction centers, STI clinics, and mobile health units,” Singh and Epstein told this news organization.

“A key step is educating primary care providers in addition to addiction medicine and emergency medicine clinicians about the updated guidelines as they interface with a large number of at-risk individuals,” they said. And the most important measure is creating clear work flows that respond to positive results to link people to treatment and cure. 

“Clinicians need to feel empowered that their work screening a patient can make a meaningful difference in both the patient’s life and in helping end this epidemic,” the two researchers explained. 

Aaron Glatt, MD, a spokesperson for the Infectious Diseases Society of America, who wasn’t involved in the study, told this news organization that the low HCV screening rates are not surprising. 

“We tend not to do well with screening. It’s not necessarily anybody’s fault, but patients don’t necessarily want to be screened. Sometimes physicians are very busy. Sometimes screening is not the most important thing for them to do. Sometimes there are processes in place that fall through,” said Glatt, chief of infectious diseases and hospital epidemiologist at Mount Sinai South Nassau, Oceanside, New York. 

“We tend to do a better job of screening in pregnant than nonpregnant women because pregnancy is a focus and there is 9 months that you can be following-up, so there is more opportunity. A healthy nonpregnant woman may not see her doctor for another year,” Glatt noted. 

“I think that many physicians are very good at screening for hepatitis C in patients that are clearly at risk,” he added. “We’re not so good at screening for people” that don’t have a clear risk but do “have risk factors.”

The study had no commercial funding. Singh, Epstein, and Glatt had no relevant disclosures.

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