Hepatology news in October 2026 included the first US Food and Drug Administration (FDA) approval of an antisense oligonucleotide for chronic hepatitis B virus (HBV) infection, a unified international definition of acute-on-chronic liver failure (ACLF), and new American College of Gastroenterology (ACG) guidance on preventive care in cirrhosis.
At the ACG 2026 Annual Scientific Meeting in Nashville, investigators presented new findings in primary biliary cholangitis (PBC), metabolic dysfunction-associated steatotic liver disease (MASLD), and cholestatic pruritus. Updates included real-world comparisons of elafibranor and obeticholic acid (OCA), cardiovascular outcomes associated with resmetirom versus semaglutide, and 96-week efruxifermin data in metabolic dysfunction-associated steatohepatitis (MASH). Additional findings addressed ileal bile acid transporter (IBAT) inhibitors in primary sclerosing cholangitis (PSC) and rare cholestatic liver diseases.
HCPLive also examined why declining US alcohol consumption may not immediately translate into fewer cases of alcohol-associated liver disease (ALD).
Here are 8 hepatology headlines from October 2026, spanning regulatory decisions, clinical guidance, research findings, and expert perspectives. For additional meeting coverage, see HCPLive's ACG 2026 recap.
Regulatory and Guideline Updates
On October 20, 2026, the FDA approved GSK's bepirovirsen (Hibsago) for chronic HBV infection, marking the first approval of an antisense oligonucleotide for the disease. Bepirovirsen is indicated for use with nucleos(t)ide analogue therapy in adults without cirrhosis who have received antiviral therapy for at least 6 months, have suppressed HBV DNA, and have hepatitis B surface antigen (HBsAg) levels of 3000 IU/mL or lower.
In the phase 3 B-Well 1 and B-Well 2 trials, functional cure occurred in 20% and 19% of patients receiving bepirovirsen, respectively, compared with no patients receiving placebo. Functional cure was defined as sustained HBV DNA suppression and HBsAg loss for at least 24 weeks after stopping all treatment. The prescribing information includes a boxed warning for serious liver reactions and thrombocytopenia.
Ahead of the approval, Tatyana Kushner, MD, discussed the B-Well findings and the pursuit of functional cure in chronic HBV on Liver Lineup.
On October 30, 2026, 5 international liver societies announced a unified definition and grading system for ACLF, published jointly in 4 journals as an 81-statement position paper. The participating organizations were the American Association for the Study of Liver Diseases (AASLD), European Association for the Study of the Liver (EASL), Asian Pacific Association for the Study of the Liver (APASL), Latin American Association for the Study of the Liver (ALEH), and Society on Liver Disease in Africa (SOLDA).
The consensus defines ACLF as liver failure, characterized by bilirubin ≥5 mg/dL and an international normalized ratio (INR) ≥1.5, accompanied by at least 1 extrahepatic organ dysfunction or failure in patients with advanced chronic liver disease. Type A ACLF occurs without prior decompensation, whereas type B occurs in patients with previously decompensated cirrhosis.
The grading system ranges from grade 1, involving liver failure and 1 organ dysfunction, to grade 3, involving liver failure and at least 2 organ failures. The societies developed the framework to address differences among regional definitions that have complicated comparisons across studies and the design of international clinical trials.
Published October 5, 2026, in the American Journal of Gastroenterology, the ACG guideline on preventive care in cirrhosis includes 18 graded recommendations and 6 key concept statements. The guideline was led by Elliot B. Tapper, MD.
Recommendations address prevention of variceal bleeding, hepatocellular carcinoma (HCC) surveillance, vaccination, and modifiable risk factors. They include carvedilol or endoscopic variceal ligation for high-risk varices, HCC surveillance with ultrasound and alpha-fetoprotein every 6 months in eligible treatment candidates, and vaccination against hepatitis A, influenza, SARS-CoV-2, and respiratory syncytial virus (RSV). The guideline also recommends smoking cessation counseling and advises against aspirin solely for HCC prevention.
In a related Liver Lineup episode, Jasmohan Bajaj, MD, MS, discussed the ACG's hepatic encephalopathy (HE) guideline, including the limitations of ammonia testing in diagnosis and the role of rifaximin alongside lactulose.
Trial Data
A propensity-matched TriNetX analysis presented at ACG 2026 found higher rates of alkaline phosphatase (ALP) normalization among patients with PBC receiving elafibranor compared with OCA. Among 444 patients in each treatment group, ALP normalized in 23.4% of those receiving elafibranor and 14.6% receiving OCA, an 8.8-percentage-point difference (P = .0009).
Median follow-up differed between groups, at 207 days for elafibranor and 365 days for OCA, limiting direct comparisons. OCA was withdrawn from the US market in September 2025.
A separate real-world analysis of 14 patients who transitioned from OCA to elafibranor reported a mean ALP reduction of 33.1% at 6 months, adding to emerging evidence on biochemical response following treatment changes.
At ACG 2026, Arun Sanyal, MD, presented 96-week findings from the phase 2b HARMONY and SYMMETRY trials evaluating efruxifermin, an Fc-FGF21 analog, in patients with MASH and varying degrees of fibrosis.
In HARMONY, which enrolled patients with F2 to F3 fibrosis, 75% of patients receiving efruxifermin 50 mg achieved at least 1-stage fibrosis improvement without worsening of MASH, compared with 24% receiving placebo (P < .001). The analysis was based on patients with an available week 96 biopsy.
In SYMMETRY, which enrolled patients with compensated cirrhosis, fibrosis improvement without MASH worsening occurred in 39% of patients receiving efruxifermin 50 mg and 15% receiving placebo (P < .01). The 28 mg dose did not achieve statistical significance in either trial, and SYMMETRY did not meet its primary end point at week 36.
A retrospective, propensity-matched TriNetX analysis presented at ACG 2026 associated resmetirom with a lower risk of major adverse cardiovascular events (MACE) compared with semaglutide in patients with MASLD or MASH and fibrosis.
The analysis included 4253 patients in each treatment group. Resmetirom was associated with lower MACE risk at 1 year (HR, 0.50; 95% CI, 0.32–0.80) and 2 years (HR, 0.61; 95% CI, 0.41–0.89). The composite outcome included myocardial infarction, ischemic stroke, and all-cause mortality.
Because the analysis was observational, the findings demonstrate an association rather than a causal cardiovascular benefit. Randomized cardiovascular outcomes data for resmetirom have not been published.
New data presented and reported in October highlighted the potential of IBAT inhibition to reduce cholestatic pruritus across different liver diseases.
In the phase 2b VISTAS trial, presented at ACG 2026 by Mitchell Shiffman, MD, 111 patients with PSC and moderate to severe pruritus received volixibat or placebo. Adult ItchRO scores decreased by 2.72 points with volixibat and 1.08 points with placebo, a between-group difference of −1.64 points (P < .001). Diarrhea occurred in 40.3% of patients receiving volixibat and 8.6% receiving placebo.
Mirum Pharmaceuticals also reported topline results from the phase 3 EXPAND trial of maralixibat, which enrolled 52 patients aged 6 months and older with pruritus associated with rare cholestatic liver diseases. In the pediatric primary analysis, maralixibat reduced worst daily itch severity by 0.98 points compared with placebo (P = .0004).
The EXPAND findings have not yet undergone peer review.
Expert Perspective
Heavy drinking declined nationally between 2022 and 2024, but the trend was different among adults aged 50 to 64, according to an analysis discussed by Brian P. Lee, MD, MAS, of Keck Medicine of USC.
In an interview with HCPLive, Lee reviewed his Annals of Internal Medicine analysis of 114,352 National Health Interview Survey respondents. Heavy drinking declined more than 8% nationally from 2022 to 2024 but increased more than 36% among adults aged 50 to 64 from 2018 to 2024.
Lee said he expects cirrhosis and liver cancer among adults older than 50 to continue increasing through the end of the decade, reflecting the delayed effects of alcohol exposure on liver disease outcomes.
HCPLive explored these trends in a 2-part ALD feature examining where ALD stands after the pandemic spike and why declining alcohol use may not yet be reflected in liver outcomes.
