The Liver Meeting 2026 Highlights Hepatitis Delta, PBC Targets, MASH Costs

Late-breaking phase 3 results in hepatitis delta, the arrival of a finite-duration therapy for chronic hepatitis B, and new questions about the cost of metabolic dysfunction–associated steatohepatitis (MASH) treatment took center stage at The Liver Meeting 2026, held November 5 to 9 in Denver, Colorado.¹ The meeting’s late-breaking program included 42 abstracts, led by 13 in hepatitis B and 10 in metabolic dysfunction–associated steatotic liver disease and MASH, with 6 more in cholestatic and autoimmune liver diseases.

For clinicians, the data point toward new treatment goals in viral hepatitis and primary biliary cholangitis (PBC), with other key findings concerning persistence, real-world spending, and inexpensive interventions in advanced liver disease.

Phase 3 Hepatitis Delta Readouts Set Up a Competitive Market

Chronic hepatitis delta virus (HDV) infection, which occurs only in people with hepatitis B, produced the meeting’s 2 pivotal-trial readouts.

In the phase 3 ECLIPSE 1 trial (NCT06903338), 124 adults across 10 countries, about 55% of whom had compensated cirrhosis, were randomly assigned 2:1 to monthly subcutaneous elebsiran plus tobevibart (Vir Biotechnology) or to delayed treatment starting at week 12.² At week 48, 44.1% of patients in the immediate-treatment arm had undetectable HDV RNA plus alanine aminotransferase (ALT) normalization compared with 0% of the delayed-treatment arm at week 12 (difference, 44.1 percentage points; 95% CI, 32.6-55.0). HDV RNA was undetectable in 79.2% of treated patients, and response rates were similar with and without cirrhosis. All participants completed 48 weeks of treatment with no serious adverse events or discontinuations, although 43.4% had flu-like symptoms, mostly after the first dose.² Vir plans to submit a regulatory package to the FDA in mid-2027, and its ECLIPSE 3 trial (NCT07142811) is comparing the regimen head-to-head with bulevirtide-gmod (Hepcludex; Gilead Sciences).³

Brelovitug (Mirum Pharmaceuticals), a monoclonal antibody that binds hepatitis B surface antigen, met its primary end point in the phase 3 portion of AZURE-1 (NCT06907290), which randomly assigned 153 treatment-naive patients at 29 sites in 11 countries to brelovitug 300 mg weekly, 900 mg every 4 weeks, or delayed treatment.⁴ At week 24, the primary end point of virologic response plus ALT normalization was met by 33 of 59 patients (56%) with weekly dosing and 29 of 65 (45%) with every-4-week dosing compared with 0 of 29 with delayed treatment (P < .001 for both). Virologic response in AZURE-1 was defined as undetectable HDV RNA or a reduction of at least 2 log₁₀ IU/mL; 17% of patients in each brelovitug arm had undetectable HDV RNA at week 24. No patients discontinued brelovitug because of adverse events.⁴

Because the 2 trials used different end point definitions and time points, their response rates cannot be compared directly. Mirum expects to file a biologics license application in the first half of 2027, pending results from its second phase 3 trial, AZURE-4 (NCT06567782), which are expected in the fourth quarter of 2026.⁵

Both candidates would enter a market that bulevirtide opened in May 2026, when it received accelerated approval as the first FDA-approved therapy for chronic HDV infection.⁶ The American Association for the Study of Liver Diseases (AASLD) also published an Expert-Based Practice Opinion on HDV diagnosis and management during the meeting.⁷ Both trials were sponsored by the drug manufacturers, and the results have not yet been published in a peer-reviewed journal.

Hepatitis B Functional Cure Moves From Trials to Practice

The meeting followed the FDA’s October 20, 2026, approval of bepirovirsen (Hibsago; GSK), the first antisense oligonucleotide for chronic hepatitis B. It is approved with ongoing nucleos(t)ide analogue therapy in certain adults without cirrhosis, and 19% of treated patients maintained viral control with undetectable hepatitis B surface antigen 24 weeks after stopping all treatment.⁸ The FDA also authorized a Roche assay as a companion diagnostic for patient selection.⁸ The drug carries a boxed warning for serious liver reactions and low platelet counts. GSK has said its list price will be disclosed after pricing and reimbursement discussions with payers conclude.⁹

Several investigational approaches aimed at the same goal reported early data. Among participants who achieved functional cure with the antisense oligonucleotide AHB-137 in the AB-10-8004 follow-up study (NCT07146100) and had data available, 16 of 17 (94.1%) maintained it at 6 months of follow-up.¹⁰ In the ELIMINATE-B study (NCT06680232), the gene-editing therapy PBGENE-HBV produced undetectable pregenomic RNA in 10 of 11 patients who were negative for hepatitis B antigen and had detectable levels at baseline, although average durability was 5 months and follow-up is ongoing.¹¹

MASH Pipeline and Real-World Persistence

In the MK-6024-013 phase 2b trial (NCT05877547) of 381 participants with stage F2 or F3 fibrosis, published in The Lancet, the glucagon-like peptide-1/glucagon receptor coagonist efinopegdutide (Merck) produced MASH resolution without worsening of fibrosis at 52 weeks in 56% to 63% of participants across 3 doses compared with 13% with placebo and 53% in an open-label reference arm of semaglutide 2.4 mg (Wegovy; Novo Nordisk).^12,13 In the RECLAIM phase 2 trial (NCT06987513), the glucagon/glucagon-like peptide-1 dual agonist pemvidutide (Altimmune) reduced heavy drinking days in patients with alcohol use disorder compared with placebo.¹⁴

For payers, persistence emerged as a cost driver. In a Markov-based model of 80,000 commercial health plan beneficiaries, 24 of every 100 members with MASH who were eligible for semaglutide remained on treatment through 72 weeks, and the authors estimated approximately $1.3 million in excess medical and pharmacy costs for each patient who responded to the optimal dose.¹⁵

Separate real-world analyses of pharmacy and claims data presented at the meeting and reported by The American Journal of Managed Care^® (AJMC^®) found 62.2% to 72.4% of patients remained on resmetirom (Rezdiffra; Madrigal Pharmaceuticals) at 12 months, although those studies used different methods and cannot be directly compared with the semaglutide model.¹⁶

Low-Cost Strategies in Cirrhosis and Alcohol-Associated Hepatitis

Two trials tested inexpensive approaches in advanced disease. In the phase 3 SACRED trial (NCT03654053) of 142 US veterans with compensated cirrhosis and probable clinically significant portal hypertension, hepatic decompensation or hepatocellular carcinoma occurred in 7 patients assigned to simvastatin and 12 assigned to placebo over a median of about 2 years (HR, 0.41; 95% CI, 0.16-1.05; P = .064).¹⁷

“In this phase 3 randomized trial, the primary end point of hepatic decompensation or HCC did not differ significantly between treatment groups, although the point estimate favored simvastatin, with a 59% lower estimated hazard,” the authors wrote.¹⁷

In the STASH II trial (NCT06919458) of 151 patients with severe alcohol-associated hepatitis at 5 centers in India, 7 days of corticosteroids produced response rates similar to 14 days (80.6% vs 77%) with a lower cumulative prednisolone dose (271.1 mg vs 458.4 mg).¹⁸ Infection (24% vs 28.9%; P = .5) and mortality (26.6% vs 19.7%; P = .3) did not differ significantly between the 7-day and 14-day groups, and 99.3% of participants were men.

PBC Treatment Targets and a National Liver Care Network

Two phase 3 trials supported alkaline phosphatase (ALP) normalization as a treatment goal in patients with PBC whose ALP remained elevated but below the traditional escalation threshold of 1.67 times the upper limit of normal.

In ELSPIRE (NCT06383403), 85.3% of patients receiving elafibranor (Iqirvo; Ipsen) achieved ALP normalization at week 52 vs 23.3% with placebo (P < .001).^19,20 In IDEAL (NCT06060665), 75.4% of patients receiving seladelpar (Livdelzi; Gilead Sciences) achieved composite ALP normalization at month 12 vs 16.1% with placebo (P < .001).^21,22 Both drugs hold accelerated approval, and neither trial measured long-term clinical outcomes.

A new AASLD and American Gastroenterological Association guideline suggests peroxisome proliferator–activated receptor agonists as second-line therapy for patients with an inadequate response to or intolerance of ursodeoxycholic acid.²³

AASLD also announced the Liver Network of Excellence, a national learning collaborative intended to reduce variation in liver care by linking care teams across academic centers, community practices, and integrated health systems through shared data.²⁴ A 12-month pilot with about 5 institutions will launch in January 2027, and expressions of interest are due January 8, 2027. According to the AASLD, findings from the pilot will guide decisions about resources and infrastructure for a broader expansion.

"The future of liver care depends on our ability to learn from one another and translate that knowledge into meaningful improvements for patients," AASLD president Saul J. Karpen, MD, PhD, FAASLD, said in a news release.²⁴ "The Liver Network of Excellence represents an important step toward building a more connected liver care community, where institutions of all sizes can collaborate, share what works, and accelerate progress toward screening, preventing, and curing liver diseases."

References

1. Hepatitis B and MASH lead late-breaking research at The Liver Meeting 2026. News release. American Association for the Study of Liver Diseases. November 5, 2026. Accessed November 11, 2026. https://www.aasld.org/hepatitis-b-and-mash-lead-late-breaking-research-liver-meetingr-2026

2. Reau N, Chow S, Jucov A, et al. Primary endpoint results of ECLIPSE 1: a randomized open-label phase 3 study evaluating efficacy and safety of elebsiran and tobevibart for chronic hepatitis delta. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5005.

3. Vir Biotechnology announces primary endpoint met in pivotal phase 3 ECLIPSE 1 trial for elebsiran and tobevibart in chronic hepatitis delta. News release. Vir Biotechnology. November 8, 2026. Accessed November 11, 2026. https://investors.vir.bio/news/news-details/2026/Vir-Biotechnology-Announces-Primary-Endpoint-Met-in-Pivotal-Phase-3-ECLIPSE-1-Trial-for-Elebsiran-and-Tobevibart-in-Chronic-Hepatitis-Delta/default.aspx

4. Kushner T, Yardeni D, Dobryanska M, et al. Efficacy and safety of brelovitug monotherapy for chronic hepatitis D: primary 24-week results from the phase 3 AZURE-1 study. Poster presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5042.

5. Mirum Pharmaceuticals announces primary endpoint met in phase 3 AZURE-1 study of brelovitug in chronic hepatitis delta virus. News release. Mirum Pharmaceuticals. September 28, 2026. Accessed November 11, 2026. https://ir.mirumpharma.com/news/news-details/2026/Mirum-Pharmaceuticals-Announces-Primary-Endpoint-Met-in-Phase-3-AZURE-1-Study-of-Brelovitug-in-Chronic-Hepatitis-Delta-Virus/default.aspx

6. FDA grants accelerated approval to Gilead’s Hepcludex (bulevirtide-gmod), the first and only approved treatment for chronic hepatitis delta virus (HDV). News release. Gilead Sciences. May 22, 2026. Accessed November 11, 2026. https://www.gilead.com/news/news-details/2026/fda-grants-accelerated-approval-to-gileads-hepcludex-bulevirtide-gmod-the-first-and-only-approved-treatment-for-chronic-hepatitis-delta-virus-hdv

7. AASLD publishes second Expert-Based Practice Opinion (EXPO), addressing diagnosis and management of hepatitis delta virus infection. News release. American Association for the Study of Liver Diseases. November 6, 2026. Accessed November 11, 2026. https://www.aasld.org/aasld-publishes-second-expert-based-practice-opinion-expo-addressing-diagnosis-and-management

8. FDA approves first-of-its-kind chronic hepatitis B treatment. News release. FDA. October 20, 2026. Accessed November 11, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-chronic-hepatitis-b-treatment

9. GSK brings promise of ‘functional cure’ to hepatitis B finish line with FDA nod for Hibsago. Fierce Pharma. Published October 2026. Accessed November 11, 2026. https://www.fiercepharma.com/pharma/gsk-brings-promise-functional-cure-hepatitis-b-finish-line-fda-nod-hibsago

10. Niu J, Gao Y, Liang X, et al. Durability of AHB-137 up to 9 month post end-of-studies in nucleos(t)ide analogue treated participants with chronic hepatitis B: first long-term follow-up report from the AB-10-8004 study. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5001.

11. Yuen MF, Streinu Cercel A, Ichim V, et al. Durable pgRNA loss in both HBeAg positive and negative patients treated with PBGENE-HBV supports path towards viral cure. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5002.

12. Schattenberg J, Lawitz E, Shankar RR, et al. A phase 2b randomized placebo-controlled study to evaluate the efficacy and safety of efinopegdutide in adults with metabolic dysfunction-associated steatohepatitis and stage 2-3 fibrosis. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5015.

13. Lawitz E, Wong V, Shankar RR, et al. Efficacy and safety of efinopegdutide in adults with metabolic dysfunction-associated steatohepatitis and stage 2–3 fibrosis: a phase 2b, randomised, placebo-controlled study. Lancet. Published online November 9, 2026. doi:10.1016/S0140-6736(26)02043-X

14. Kranzler H, Tomah S, Simmons WK, et al. Efficacy and safety of pemvidutide in the treatment of adults with alcohol use disorder: results from RECLAIM, a 24-week phase 2 randomized double-blind placebo-controlled trial. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5013.

15. Calderon F, Lachuk L, Atreja N, Lobo F. Estimating real world clinical and economic implications of GLP-1 persistence and dosing in metabolic dysfunction-associated steatohepatitis (MASH). Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Hepatology. 2026;84(suppl 1):3522.

16. McNulty R. Pharmacy, claims data show high resmetirom persistence in MASH. AJMC. Published November 9, 2026. Accessed November 11, 2026. https://www.ajmc.com/view/pharmacy-claims-data-show-high-resmetirom-persistence-in-mash

17. Kaplan D, Baffy G, Aytaman A, et al. Simvastatin for prevention of hepatic decompensation or hepatocellular carcinoma in compensated cirrhosis with probable clinically significant portal hypertension: a phase III randomized trial. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5004.

18. Kulkarni A, Kumar K, Roy A, et al. Seven or fourteen days of corticosteroids for severe alcohol-associated hepatitis: a double-blind, placebo-controlled, randomized, multicenter study (STASH II). Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5030.

19. Kowdley KV, Lawitz E, Bowlus CL, et al. Elafibranor to normalize alkaline phosphatase in patients with primary biliary cholangitis and incomplete response to ursodeoxycholic acid: results from the phase III randomized controlled ELSPIRE trial. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5019.

20. Kowdley KV, Lawitz E, Bowlus CL, et al. Treatment with elafibranor to normalize alkaline phosphatase in patients with primary biliary cholangitis and incomplete response to ursodeoxycholic acid: results from the phase III randomized controlled ELSPIRE trial. Hepatology. Published online November 5, 2026. doi:10.1097/HEP.0000000000001906

21. Levy C, Carroll S, Kowdley K, et al. Seladelpar for alkaline phosphatase normalization in primary biliary cholangitis: results from the IDEAL phase III randomized-controlled trial. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO. Abstract 5007.

22. McNulty R. Phase 3 data back ALP normalization as treatment goal in PBC. AJMC. Published November 9, 2026. Accessed November 11, 2026. https://www.ajmc.com/view/phase-3-data-back-alp-normalization-as-treatment-goal-in-pbc

23. AASLD and AGA offer first medication-focused guideline for treating PBC. News release. American Association for the Study of Liver Diseases. October 22, 2026. Accessed November 11, 2026. https://www.aasld.org/aasld-and-aga-offer-first-medication-focused-guideline-treating-pbc

24. AASLD announces Liver Network of Excellence, a new national initiative to transform liver care. News release. American Association for the Study of Liver Diseases. November 6, 2026. Accessed November 11, 2026. https://www.aasld.org/aasld-announces-liver-network-excellence-new-national-initiative-transform-liver-care