Recent Updates in Chronic Liver Disease (2024-2026)

1. Nomenclature and Epidemiology: The SLD Shift

• MASLD - Metabolic dysfunction-associated steatotic liver disease (encompasses what was NAFLD)
• MASH - Metabolic dysfunction-associated steatohepatitis (replaces NASH)
• MetALD - Metabolic alcohol-related liver disease (new subtype for patients with both metabolic risk and moderate alcohol use)

2. MASLD/MASH: Two FDA-Approved Drugs Now Available

Resmetirom (Rezdiffra) - March 2024

• First-ever FDA-approved drug specifically for MASH with liver fibrosis (F2-F3)
• Mechanism: selective thyroid hormone receptor-beta (THR-β) agonist
• Acts on hepatic lipid metabolism - reduces liver fat and fibrosis
• In 2025, new data showed significant reductions in liver stiffness even in compensated MASH cirrhosis (F4)
• A systematic review confirmed efficacy and a favorable safety profile [PMID: 39187533]

Semaglutide (Wegovy 2.4 mg/week SC) - August 2025

• FDA granted accelerated approval for noncirrhotic MASH with moderate-to-advanced fibrosis (F2-F3) - the first GLP-1 receptor agonist approved for this indication
• Based on interim results of the ESSENCE Phase 3 trial (72 weeks, 2.4 mg/week SC):
  • MASH resolution without fibrosis worsening: 62.9% vs. 34.3% (placebo), p<0.001
  • ≥1 stage fibrosis reduction: 36.8% vs. 22.4% (placebo), p<0.001
• Final approval awaits long-term outcomes from the full ESSENCE trial
• AASLD November 2025 Practice Guidance Update formally incorporated semaglutide [PMID: 41201884], recommending:
  • Patient selection via non-invasive tests (NITs): VCTE 8-15 kPa, MRE 3.1-4.4 kPa, or ELF 9.2-10.5 - not liver biopsy for most patients
  • NOT approved for MASH cirrhosis (VCTE >20 kPa)
  • Lifestyle modification remains the cornerstone; semaglutide adds to it, does not replace it
  • Monitor for GI side effects, pancreatitis, gallbladder disease, and lean mass loss

GLP-1 Therapy - Meta-analytic Evidence

Pipeline: Efruxifermin and Pemvidutide

• Efruxifermin (FGF21 analogue): Phase 2b data (2025) showed fibrosis reduction in MASH cirrhosis
• Pemvidutide (dual GLP-1/glucagon agonist): Significant MASH resolution and weight loss at 24 weeks in Phase 2b; advancing to Phase 3

3. Key Guideline Updates (2024-2025)

EASL-EASD-EASO MASLD Guidelines (2024)

• Nomenclature transition, risk stratification, and treatment algorithms
• Emphasis on metabolic comorbidity management (obesity, T2DM, dyslipidemia)
• Non-invasive fibrosis assessment preferred over biopsy in most patients [PMID: 38851997]

APASL MAFLD Guidelines (2025)

EASL Autoimmune Hepatitis Guidelines (2025)

• Diagnostic criteria and updated immunosuppressive protocols
• AIH variant syndromes
• Surveillance for portal hypertension and HCC in AIH-associated cirrhosis
• Role of liver transplantation in decompensated AIH cirrhosis [PMID: 40348684]

AASLD/IDSA Chronic Hepatitis B Guidelines (November 2025)

• Prevention: Maternal-to-infant transmission and horizontal transmission
• Surveillance: HCC surveillance in HBsAg-positive patients co-infected with HCV, HDV, or HIV; surveillance after HBsAg loss
• Treatment: Recommendations on immune-tolerant and "indeterminate" phase patients; antiviral withdrawal criteria [PMID: 41186418]

Chinese Cirrhosis Guidelines (2025)

4. Cirrhosis Complications: Updated Management

Portal Vein Thrombosis (PVT) in Cirrhosis - AGA 2025

• Asymptomatic compensated cirrhosis: no routine PVT screening needed
• Doppler-confirmed PVT: confirm with CT/MRI, exclude malignancy
• Acute PVT with intestinal ischemia: urgent anticoagulation
• Observation (re-imaging q3 months) for: <50% occlusion of main portal vein, splenic, or mesenteric veins
• Anticoagulation preferred for: >50% occlusive recent PVT, main portal vein, or mesenteric involvement
• DOACs acceptable in Child-Pugh A and B (convenient, INR-independent dosing)
• Cavernous transformation (chronic complete occlusion): anticoagulation not advised

Non-Invasive Diagnostics

• FDA accepted FibroScan liver stiffness measurement (LSM) as a "reasonably likely surrogate endpoint" for MASH trials (September 2025), enabling faster drug development
• Position paper on ultrasound elastography implementation in clinical practice issued jointly by SIAD and AFEF (2025) [PMID: 40210513]
• Non-invasive methods (VCTE, MRE, ELF) are now the preferred approach over liver biopsy for fibrosis staging in both MASLD and portal hypertension assessment in NAFLD/MASLD cirrhosis [PMID: 39911662]

HRS Management

5. Hepatitis B: Moving Toward Functional Cure

• AASLD/IDSA November 2025 guideline expands treatment criteria for immune-tolerant and indeterminate-phase patients, and refines antiviral discontinuation criteria
• AHB-137 (antisense oligonucleotide by AusperBio): Phase 3 initiated (July 2025) in China; Phase 2a showed 30% functional cure rate (HBsAg loss) at 72 weeks in patients with baseline HBsAg 100-1000 IU/mL
• TherVacB (therapeutic vaccine): EU-funded Phase 2 trial began June 2025 across 81 patients in 5 countries - first therapeutic vaccine to aim for functional cure
• Pegbing approved in China (October 2025): first domestically developed CHB drug targeting functional cure, used in combination with nucleos(t)ide analogues

6. Liver Transplantation

• Updated candidate evaluation criteria
• Non-graft-related post-transplant complications
• Diagnosis and management of graft-related complications

Summary Table

• Semaglutide for MASH AASLD guidance update [PMID: 41201884]
• EASL-EASD-EASO MASLD guidelines [PMID: 38851997]
• APASL MAFLD guidelines [PMID: 40016576]
• EASL AIH guidelines [PMID: 40348684]
• AGA PVT in cirrhosis update [PMID: 39708000]
• Global SLD prevalence meta-analysis [PMID: 40204206]
• GLP-1 therapies in MASLD/MASH meta-analysis [PMID: 40489581]