Recent updates in chronic liver disease
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"chronic liver disease" AND management
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chronic liver disease recent updates 2025 2026 guidelines treatment
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"MASLD" OR "MASH" AND resmetirom treatment
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"liver cirrhosis" AND "portal hypertension" management
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resmetirom MASH approval 2025 2026 MASLD new drugs hepatitis B treatment updates
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"hepatocellular carcinoma" surveillance diagnosis 2025
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semaglutide MASH FDA approval August 2025 EASL hepatitis B 2025 guideline updates portal hypertension
Here is a comprehensive, up-to-date review of recent updates in chronic liver disease, organized by major topic.
Recent Updates in Chronic Liver Disease (2024-2026)
1. MASLD/MASH - Nomenclature, Diagnosis, and Pharmacotherapy
New Nomenclature (2023, now widely adopted)
The field moved from NAFLD/NASH to a metabolic-based terminology:
- MASLD (Metabolic dysfunction-Associated Steatotic Liver Disease) - replaces NAFLD
- MASH (Metabolic dysfunction-Associated Steatohepatitis) - replaces NASH
- Diagnosis of MASLD requires hepatic steatosis plus at least one of five cardiometabolic risk factors (overweight/obesity, T2DM, hypertension, dyslipidemia, metabolic dysregulation)
- This renaming also introduced MetALD (for those with significant alcohol use) and SLD (Steatotic Liver Disease) as the umbrella term
- Adopted by EASL, AASLD, and most major societies globally
Global Prevalence
A 2025 meta-analysis (PMID: 40204206) confirmed high global prevalence of steatotic liver disease and its associated subtypes, underscoring the public health burden.
FDA-Approved Pharmacotherapies - Two Major Milestones
| Drug | Class | Approval | Indication | Trial |
|---|---|---|---|---|
| Resmetirom (Rezdiffra) | THR-β agonist | March 2024 | Noncirrhotic MASH with F2-F3 fibrosis | MAESTRO-NASH |
| Semaglutide 2.4 mg (Wegovy) | GLP-1 RA | August 2025 | Noncirrhotic MASH with F2-F3 fibrosis | ESSENCE trial |
Resmetirom was the first-ever FDA-approved liver-directed therapy for MASH. It works by mimicking thyroid hormone at the beta receptor in the liver, reducing hepatic lipogenesis and steatosis. Dosing is weight-based: 80 mg/day if <100 kg, 100 mg/day if ≥100 kg.
Semaglutide (Wegovy) became the first GLP-1 to gain MASH approval. At 72 weeks in the ESSENCE trial:
- 62.9% achieved MASH resolution without fibrosis worsening (vs. 34.3% placebo)
- 36.8% achieved ≥1 stage fibrosis reduction without MASH worsening (vs. 22.4% placebo)
- Accelerated approval; confirmation awaits long-term outcomes data
AASLD updated its Practice Guidance in November 2025 for semaglutide (PMID: 41201884) and October 2024 for resmetirom, with patient selection criteria based on non-invasive tests (NITs) - liver biopsy is no longer required.
Non-Invasive Diagnostics Milestone
In September 2025, the FDA accepted the Liver Stiffness Measurement by VCTE (FibroScan) as a "reasonably likely surrogate endpoint" in MASH drug development trials - the first NIT ever accepted for this purpose. This will accelerate future trial design.
Pipeline Therapies
- Efruxifermin (FGF21 analogue): Phase 2b showing fibrosis reduction in MASH cirrhosis
- Pemvidutide (GIP/GLP-1 dual agonist): Phase 2b completed, Phase 3 planned
- Retatrutide (triple GLP-1/GIP/glucagon agonist): Phase 3 ongoing
- Combination regimens (e.g., resmetirom + DGAT2/ACC inhibitor) under study
- Unmet need: No approved therapy for cirrhotic MASH (F4) yet
New Guidelines
- EASL-EASD-EASO CPG on MASLD (J Hepatol, 2024) - PMID: 38851997
- APASL CPG on MAFLD/MASLD (Hepatol Int, April 2025) - PMID: 40016576
- Latin American working group updated MASLD recommendations (Ann Hepatol, 2025) - PMID: 40089151
- Global Consensus Recommendations for MASLD/MASH (Gastroenterology, 2025) - PMID: 40222485
2. Cirrhosis - Complications and Management
Chinese Guidelines for Cirrhosis Management (2025)
Published in J Clin Transl Hepatol, covering:
- Early etiology-directed therapy and anti-fibrotic strategies
- Ascites: Updated diuretic protocols; albumin infusion expanded role
- Hepatic Encephalopathy (HE): Lactulose + rifaximin + L-ornithine-L-aspartate; address precipitants
- SBP: Empiric antibiotics + albumin (1.5 g/kg day 1, then 1 g/kg day 3)
- HRS: Terlipressin + albumin as first-line; consider TIPS or transplant
- Portal Vein Thrombosis (PVT): Anticoagulation (DOACs or LMWH preferred); TIPS in selected cases
EASL Clinical Practice Guidelines on TIPS (J Hepatol, July 2025) - PMID: 40180845
Covers TIPS indications (refractory ascites, variceal bleeding), covered stent use, and contraindication assessment.
AGA Clinical Practice Update - Portal Vein Thrombosis (Gastroenterology, Feb 2025) - PMID: 39708000
- DOACs now preferred for PVT in cirrhosis over LMWH in most cases
- Early anticoagulation for acute PVT even in non-occlusive disease
ACG Clinical Guideline - Perioperative Risk in Cirrhosis (Am J Gastroenterol, 2025) - PMID: 40899690
Structured risk assessment framework (MELD-Na, Child-Pugh, VOCAL-Penn score) for surgical planning.
Concept of Recompensation
Growing recognition that cirrhosis is not uniformly irreversible - recompensation (return from decompensated to compensated state) can occur, particularly after cure of hepatitis C, alcohol cessation, or antiviral therapy in HBV. This has treatment and prognostic implications.
3. Hepatitis B (HBV)
AASLD-IDSA Practice Guideline on Chronic Hepatitis B (November 2025) - PMID: 41186418
Six PICO-based evidence-graded recommendations addressing:
- Maternal-to-infant transmission prevention: Tenofovir prophylaxis in third trimester for high-viremia mothers
- Indeterminate/immune-tolerant phase: More nuanced criteria for when to treat (controversial zone)
- Antiviral withdrawal: Evidence-based criteria for discontinuation of nucleoside analogues
- Surveillance after HBsAg loss: HCC screening remains warranted in cirrhotics and high-risk populations
- Co-infection surveillance (with HCV, HDV, HIV): Tailored recommendations
EASL Clinical Practice Guidelines on HBV (J Hepatol, August 2025) - PMID: 40348683
Updated European guidelines in alignment with AASLD, emphasizing finite therapy duration and expanded treatment indications.
4. Autoimmune Hepatitis (AIH)
EASL Clinical Practice Guidelines on AIH (J Hepatol, August 2025) - PMID: 40348684
- Updated first-line treatment: Prednisolone + azathioprine remains standard
- Budesonide (non-cirrhotic AIH): Preferred to minimize systemic steroid side effects
- Mycophenolate mofetil as second-line for azathioprine intolerance
- Monitoring strategies and criteria for treatment withdrawal
5. Hepatocellular Carcinoma (HCC)
EASL Clinical Practice Guidelines on HCC (J Hepatol, February 2025) - PMID: 39690085
Key updates include:
- Surveillance: Ultrasound + AFP every 6 months remains standard; MRI surveillance considered in high-risk (cirrhosis + poor ultrasound window)
- Systemic therapy: Atezolizumab + bevacizumab (Atezo/Bev) or durvalumab + tremelimumab as preferred first-line systemic options for advanced HCC
- Immune checkpoint inhibitors (ICIs) pre-transplant: A 2025 meta-analysis (PMID: 38996924) showed careful patient selection needed due to post-transplant rejection risk
- Expanding role of TACE + systemic therapy combinations in intermediate-stage HCC
6. Liver Transplantation
AASLD-AST Practice Guidelines (December 2025)
Two new guidelines:
- Candidate Evaluation for Adult Liver Transplantation
- Diagnosis and Management of Graft-Related Complications (PMID: 40844852)
Covering updated MELD exceptions, frailty assessment, post-transplant immunosuppression protocols, and management of recurrent disease (including MASH and HCV recurrence).
7. Primary Biliary Cholangitis (PBC) and Primary Sclerosing Cholangitis (PSC)
- Obeticholic acid (OCA) remains second-line in PBC for UDCA non-responders
- Elafibranor (PPAR-α/δ agonist): Approved for PBC in 2024 in adults with inadequate UDCA response
- Seladelpar (PPARδ agonist): Approved for PBC in 2024 (accelerated approval)
- PSC: No approved therapy yet; ongoing trials with nor-UDCA, immunomodulators, and microbiome-targeted interventions
- Active research into gut-liver axis in PSC pathogenesis
8. Non-Cirrhotic Portal Hypertension
APASL Recommendations (Hepatol Int, December 2024) - PMID: 39546143
Updated diagnostic and management recommendations for non-cirrhotic portal fibrosis (NCPF)/idiopathic portal hypertension, including distinction from cirrhosis and specific anticoagulation guidance.
Summary Table of Major 2024-2026 Guidelines
| Topic | Society | Year | Key Update |
|---|---|---|---|
| MASLD | EASL/EASD/EASO | 2024 | New nomenclature; NIT-based diagnosis |
| MASLD | AASLD | 2024/2025 | Resmetirom & semaglutide guidance |
| HBV | AASLD/IDSA | 2025 | Treat indeterminate phase; antiviral withdrawal |
| HBV | EASL | 2025 | Harmonized with AASLD; finite therapy |
| HCC | EASL | 2025 | Atezo/Bev first-line; ICI pre-transplant caution |
| AIH | EASL | 2025 | Budesonide, MMF second-line |
| TIPS | EASL | 2025 | Updated indications and technique |
| Cirrhosis | China | 2025 | Comprehensive complication management |
| Liver Transplant | AASLD/AST | 2025 | Graft complication management |
| PVT | AGA | 2025 | DOACs preferred over LMWH |
| NCPF/IPH | APASL | 2024 | Diagnostic criteria, anticoagulation |
The most transformative development in the field is the arrival of two approved pharmacotherapies for MASH (resmetirom in 2024 and semaglutide in 2025), ending decades with no liver-directed drugs for this increasingly prevalent condition. The pipeline for cirrhotic MASH (F4) remains an unmet need, with several phase 2/3 trials underway.
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