The AASLD 2025 Liver Meeting^® (7–11 November, Washington, D.C., USA) delivered a breadth of early- and late-phase data across metabolic liver disease, cholestatic conditions, liver failure, and rare liver diseases. This year’s findings reflected a rapidly evolving therapeutic landscape, with meaningful progress in mechanistic understanding, emerging signals of disease modification, and increasing momentum toward more precise, multi-pathway strategies across multiple liver conditions.

Metabolic dysfunction–associated steatohepatitis

Research in metabolic dysfunction–associated steatohepatitis (MASH) continues to broaden, with novel mechanisms advancing alongside renewed interest in fibrosis regression. This year’s presentations emphasized metabolic modulation, endocrine approaches, RNA technologies and potential anti-fibrotic effects.

Key presentations

• In a Phase 2a study (NCT06054815) in presumed MASH, vanoglipel (DA-1241), an oral G protein-coupled receptor 119 (GPR119) agonist, demonstrated meaningful reductions in HbA1c, and improvements in fibrosis, liver inflammation and plasma lipidomic profiles at 16 weeks.¹ Highlighting the ability of vanoglipel to target hepatic and metabolic drivers of MASH.
• In an open-label extension study (NCT04880031), once-monthly dosing with efimosfermin alfa 300mg, a fibroblast growth factor 21 (FGF21) analogue, sustained fibrosis improvement and MASH resolution over 48 weeks in MASH with F2–F3 fibrosis, underscoring the promise of long-acting endocrine-based therapy.² Improvements in fibrosis, liver injury and cardiometabolic markers were observed, while efimosfermin was well tolerated with no new safety signals.
• PK–PD modelling demonstrated that monthly 100mg or quarterly 200mg dosing of the GalNAc–siRNA therapeutic, GSK4532990 was sufficient to sustain reductions in hepatic HSD17B13 protein and serum alanine aminotransferase (ALT) over dosing intervals.³ These findings support the dosing strategy in the ongoing HORIZON Phase 2b study (NCT05583344).
• In a secondary analysis of the FASCINATE-2 Phase 2b study (NCT04906421), denifanstat, an oral fatty acid synthase (FASN) inhibitor, had a ≥2-stage fibrosis improvement without MASH worsening in around one-third of stage 3 fibrosis patients.⁴ In participants with advanced (stage 4) disease, over one-third had a ≥1-stage fibrosis improvement without MASH worsening, 85% had a ≥1 qFibrosis stage regression, while several biomarkers decreased in these participants.

Primary biliary cholangitis

Primary biliary cholangitis (PBC) research this year focused on long-term disease modification and symptomatic burden, particularly pruritus and fatigue.

Key presentations

• Interim 36-month results from the ongoing ASSURE (NCT03301506) open-label extension study show that seladelpar can maintain or improve liver stiffness measurements, a key marker of disease progression, in patients with PBC.⁵ These results highlight seladelpar, a selective peroxisome proliferator-activated receptor (PPAR)-delta agonist, as a therapeutic option with potential to mitigate long-term fibrotic progression. Seladelpar is already approved for second-line treatment of PBC following the positive findings from the RESPONSE study (NCT04620733).
• In the Phase 3 GLISTEN study (NCT04950127), linerixibat improved biomarkers of bile acid synthesis and reabsorption, increasing serum C4 and reducing FGF-19, and potential mediators of pruritus, reducing total serum bile acids, autotaxin, and interleukin-31, in patients with PBC.⁶ These effects were also reversible upon discontinuation of linerixibat.
• Interim findings from the ELATIVE (NCT04526665) long-term, open-label extension study suggested sustained biochemical response with elafibranor, as well as stabilisation of fibrosis markers, and improvement in symptoms, including fatigue and pruritus in patients with PBC.⁷ Elafibranor is a PPARα/PPARδ agonist already approved as a second-line treatment for PBC, following positive results from ELATIVE.

Liver failure

Therapeutic options for acute-on-chronic liver failure (ACLF) and advanced cirrhosis remain limited, and this year’s data underscored growing efforts to target the underlying metabolic, inflammatory and structural drivers of disease progression. Interest continued to build around multi-pathway interventions, as well as pharmacological strategies aimed at modifying fibrosis and portal hypertension in compensated populations.

Key presentations

• Findings from a preclinical study confirm the efficacy of NTZ/G1090N 300mg/kg, administered post-ACLF trigger, in reducing systemic inflammation and restoring organ function in an ACLF disease model.⁸
• A post-hoc analysis of the 96-week, placebo-controlled Phase 2b SYMMETRY trial (NCT05039450) showed that efruxifermin, an FGF21 analogue, improved histological fibrosis and reduced septa area, a marker of disease severity, based on quantitative digital pathology in participants with compensated cirrhosis due to MASH.⁹
• A 16-week, randomized, placebo-controlled study evaluated the efficacy of a combination of zibotentan and dapagliflozin in patients with cirrhosis and clinically significant portal hypertension.¹⁰ Results showed that the combination treatment did not reduce hepatic venous pressure gradient; however, dapagliflozin monotherapy demonstrated improvements in fluid retention in cirrhosis.

Rare liver diseases

Rare liver diseases continued to receive growing attention, with new data highlighting progress across cholestatic, immune-mediated and paediatric conditions where therapeutic options remain limited.

Key presentations

• There are currently no approved therapies for biliary atresia, a rare, life-threatening, progressive obstructive cholangiopathy in infants.¹¹ Updates were presented from the first global Phase 3 programme evaluating the long-term efficacy and safety of odevixibat, an ileal bile acid transporter inhibitor, for biliary atresia. The Phase 3 study BOLD (NCT04336722) is estimated to be completed mid-2026, with the open-label extension study BOLD-EXT (NCT05426733) continuing until 2028.
• Interim results from the open-label extension of the ELMWOOD Phase 2 trial (NCT05627362) indicated that elafibranor remained well tolerated in participants with primary sclerosing cholangitis (PSC).¹² All participants receiving elafibranor —regardless of their original treatment assignment—showed reductions in biochemical markers of cholestasis and pruritus.
• A post hoc, subgroup analysis of the Phase 3 MITIGATE trial (NCT04540497) showed that CD19-targeted B cell depletion with inebilizumab markedly reduced flares and steroid use in IgG4-related disease with pancreatic or hepatobiliary involvement, with higher rates of flare-free, treatment-free remission compared with placebo.¹³ Biomarker patterns preceding organ-specific flares were also identified.

Conclusion

The Liver Meeting^® 2025 reinforced a shift toward targeted, multi-pathway and symptom-focused therapeutic strategies across liver disease. From emerging anti-fibrotic activity in MASH to expanded therapeutic investigation in cholestatic disorders, advances in the management of liver failure, and growing momentum in rare disease research, the field continues to move steadily toward more personalized and mechanistically grounded care.

References

1. Loomba R, Kim M-K, Kim HH, et al. DA-1241, A GPR119 Agonist, Demonstrates Hepatoprotective Effects Through Improving Inflammation And Metabolism In The Liver: A 16-Week Randomized Placebo-Controlled Trial In Presumed Metabolic Dysfunction Associated Steatohepatitis (MASH) Patients. Hepatology. 2025;82(S1):S1–S2308. Abstract no. 4012.
2. Noureddin M, Kowdley K, Kutch K, et al. Once-Monthly Efimosfermin Alfa For Up To 48 Weeks In Metabolic Dysfunction-Associated Steatohepatitis With F2/F3 Fibrosis: Results From A Phase 2, Open-Label Extension Study. Hepatology. 2025; ePub ahead of print. Doi: 10.1097/HEP.0000000000001589. Abstract no. 5011.
3. Irurzun-Arana I, Chandasana H, Lopez-Barrera N, et al. GSK4532990 Pharmacokinetic–Pharmacodynamic (PK–PD) Modeling Supports Quarterly And Monthly Sirna Dosing For Mash In The Horizon Phase 2b Study. Hepatology. 2025;82(S1):S1–S2308. Abstract no. 4099.
4. Loomba R, Tsai W-W, Vinod Gupta S, et al. Denifanstat Elicited A Significant 2-Stage Improvement In Fibrosis In F3 Mash Patients, And Improved Liver Fibrosis And Biomarkers In Qfibrosis Stage 4 Mash Patients: Secondary Analysis Of Phase 2b FASCINATE-2 Study. Hepatology. 2025;82(S1):S1–S2308. Abstract no. 4011.
5. Bowlus C, Hirschfield G, Villamil A, et al. Disease Control As Evidenced By Longitudinal Transient Elastography Measurements In The Assure Study: 36 Months Of Treatment With Seladelpar Is Associated With Stable Or Improved Liver Stiffness In Patients With Primary Biliary Cholangitis. Hepatology. 2025; ePub ahead of print. Doi: 10.1097/HEP.0000000000001589. Abstract no. 5031.
6. Kremer A, Bowlus C, Lennie J, et al. Impact Of Linerixibat On Pharmacodynamic Biomarkers And Mediators Of Cholestatic Pruritus In Primary Biliary Cholangitis (PBC) In The Phase 3 GLISTEN Study. Hepatology. 2025;82(S1):S1–S2308. Abstract no. 0214.
7. Levy C, Akarca U, Alvares-da-Silva MR, et al. Long-term treatment with elafibranor leads to biochemical and symptomatic improvements for at least 3 years in patients with primary biliary cholangitis. Hepatology. 2025; ePub ahead of print. Doi: 10.1097/HEP.0000000000001589. Abstract no. 5016.
8. Bobowski-Gerard M, Delataille P, Debaecker S, et al. Efficacy Of Nitazoxanide (NTZ) On Systemic Inflammation And Organ Function In Disease Models Of Acute-On-Chronic Liver Failure (ACLF) When Administered Post-ACLF Trigger. Hepatology. 2025;82(S1):S1–S2308. Abstract no. 4165.
9. Rinella M, Choudhury Y, Gan G, et al. Efruxifermin Reduced Fibrosis And Septa Area By Quantitative Digital Pathology In Participants With Compensated Cirrhosis Due To MASH: Results From The 96-Week, Placebo-Controlled, Phase 2b SYMMETRY Trial. Hepatology. 2025; ePub ahead of print. Doi: 10.1097/HEP.0000000000001589. Abstract no. 5024.
10. Mandorfer M, Procopet B, Garcia-Pagán JC, et al. Effects Of Zibotentan And Dapagliflozin In Patients With Cirrhosis And Clinically Significant Portal Hypertension: A Randomized Placebo-Controlled 16-Week Study. Hepatology. 2025; ePub ahead of print. Doi: 10.1097/HEP.0000000000001589. Abstract no. 5027.
11. Karpen S, Yu J, Verkade H. BOLD And BOLD-EXT, The First Global Phase III Clinical Program To Evaluate The Long-Term Efficacy And Safety Of Odevixibat In Infants With Biliary Atresia After Kasai Hepatoportoenterostomy – Study Design And Current Status. Hepatology. 2025;82(S1):S1–S2308. Abstract no. 4504.
12. Bowlus C, Levy C, Abouda G. Long-Term Data Of Elafibranor In Primary Sclerosing Cholangitis: Interim Safety And Efficacy Data From The Ongoing Open label Extension Of The ELMWOOD Phase II Trial. Hepatology. 2025;82(S1):S1–S2308. Abstract no. 0005.
13. Culver E, Stone J, Khosroshahi A. Safety And Efficacy Of Inebilizumab In IGG4 Related Disease In Participants With Hepatic, Pancreatic, And Biliary Involvement: Results From The Phase 3 Mitigate Trial. Hepatology. 2025; ePub ahead of print. Doi: 10.1097/HEP.0000000000001589. Abstract no. 5008.