Recent Updates in Chronic Liver Disease (CLD) - 2024 to 2026

1. Nomenclature Change: NAFLD/NASH → MASLD/MASH

• NAFLD (Non-Alcoholic Fatty Liver Disease) is now called MASLD - Metabolic dysfunction-Associated Steatotic Liver Disease
• NASH is now called MASH - Metabolic dysfunction-Associated SteatoHepatitis
• MAFLD (Metabolic-Associated Fatty Liver Disease) remains in use primarily in Asia-Pacific guidelines (APASL 2025)
• This reflects recognition that metabolic dysfunction (not mere alcohol abstinence) is the key driver

2. MASLD/MASH - Major Therapeutic Breakthroughs

First FDA/EMA-Approved Drug for MASH

• Resmetirom (Rezdiffra) - a thyroid hormone receptor-beta (THR-β) agonist - is the first drug approved specifically for MASH with F2-F3 fibrosis. Phase 3 (MAESTRO-NASH) trial showed significant histological improvement (fibrosis regression + MASH resolution) [PMID: 40066918]
• Semaglutide (GLP-1 agonist, ESSENCE trial) showed MASH resolution and fibrosis improvement in Phase 3 data - became the second agent with Phase 3 efficacy
• Tirzepatide (GLP-1/GIP dual agonist, SYNERGY-NASH trial) also demonstrated strong histological efficacy in Phase 3

2026 Guidelines (AISF, Japan) Key Pharmacological Recommendations [PMID: 41864758, 42120590]:

• Lifestyle modification (caloric restriction + exercise) remains the cornerstone
• Pharmacotherapy is reserved for patients with high-risk MASH (at-risk MASH = MASH + F2+ fibrosis, or elevated NAS with metabolic risk)
• The AISF STEPS-MASH framework provides a structured identification-selection-monitoring approach for drug-eligible patients

Diagnostic Updates (MASLD 2026 Japan Guidelines) [PMID: 42120590]:

• FIB-4 index is the validated first-line noninvasive tool for fibrosis risk stratification (widely accessible)
• Secondary assessment with elastography (vibration-controlled transient elastography - VCTE/FibroScan) for patients with elevated FIB-4
• Liver biopsy is NOT routinely required for MASLD diagnosis, but remains essential for:
  • Confirming at-risk MASH before pharmacotherapy
  • Resolving discrepancies between noninvasive tests
  • Differentiating from other CLD
• Advanced fibrosis stage is the single most important prognostic factor for liver-related mortality and HCC risk

3. Hepatitis B - Updated Guidelines 2025 (AASLD/IDSA)

• Expanded treatment indications - lower thresholds for initiating antiviral therapy (tenofovir/entecavir) even in patients with normal ALT but significant fibrosis
• HBsAg loss as the functional cure endpoint - newer agents targeting HBsAg (capsid assembly modulators, RNA-based therapies) are in trials
• Emphasis on preventing HCC through aggressive treatment and surveillance even post-HBsAg loss in cirrhotic patients
• Guidance updated on managing immune-tolerant phase patients

4. Post-HCV Cure Management - EASL Position Paper 2024 [PMID: 38845253]

• Patients without advanced fibrosis: standard follow-up, can be discharged from hepatology if SVR confirmed and no cofactors
• Patients with compensated advanced CLD (cACLD)/cirrhosis: lifelong surveillance for HCC every 6 months (ultrasound ± AFP), even after SVR
• HCC risk does not disappear with SVR in cirrhotic patients - remains elevated for years
• Screening for esophageal varices still required post-SVR in cirrhotics
• Reinfection monitoring in at-risk groups (PWID, MSM) with regular HCV RNA testing

5. Portal Hypertension - New EASL TIPS Guidelines 2025 [PMID: 40180845]

• TIPS (Transjugular Intrahepatic Portosystemic Shunt) guidelines fully updated:
  • Pre-emptive/early TIPS (within 72 hours of acute variceal bleed in Child-Pugh B with active bleeding or Child-Pugh C <14) is now strongly recommended
  • Covered stent grafts (PTFE-covered) are standard over bare metal stents - lower risk of shunt dysfunction
  • TIPS for refractory ascites: 8 mm TIPS preferred over large-volume paracentesis as definitive therapy
  • Carvedilol is now preferred over propranolol for non-selective beta-blocker prophylaxis of variceal bleeding (lower HVPG reduction)

APASL Acute Variceal Bleeding Guidelines 2025 [PMID: 40886248]:

• Terlipressin remains first-line vasoactive drug (with demonstrated mortality benefit)
• Antibiotic prophylaxis (ceftriaxone) for all cirrhotic patients with acute variceal bleed - reduces bacterial infections and improves survival
• Band ligation + vasoactive drug is the combination standard of care

AGA Portal Vein Thrombosis Update 2025 [PMID: 39708000]:

• Anticoagulation (LMWH or NOACs) now recommended for most cirrhotic patients with acute/subacute PVT (portal vein thrombosis)
• DOACs (rivaroxaban, apixaban) are increasingly used as alternatives to LMWH

6. Autoimmune Hepatitis - EASL Guidelines 2025 [PMID: 40348684]

• First-line treatment remains azathioprine + prednisolone (or budesonide in non-cirrhotic)
• Updated guidance on mycophenolate mofetil (MMF) as a valid second-line agent in azathioprine-intolerant patients
• Clearer algorithms for AIH-associated cirrhosis: surveillance for HCC and portal hypertension now formally recommended
• Guidance now covers AIH in children and AIH with overlap syndromes (PBC-AIH, PSC-AIH overlap)
• Liver transplant listing criteria in decompensated AIH cirrhosis are updated

7. Perioperative Management of Cirrhosis - Two New 2025 Guidelines

ACG Guideline: Perioperative Risk in Cirrhosis [PMID: 40899690]

• MELD-Na is the preferred preoperative risk stratification tool (superior to Child-Pugh for most surgeries)
• MELD-Na >15 warrants hepatology consultation pre-operatively
• Elective surgery should be deferred if MELD-Na >20 unless benefit outweighs risk
• Specific recommendations for laparoscopic vs open approach, and hernia repair in cirrhotics

EASL Guideline: Extrahepatic Abdominal Surgery in Cirrhosis [PMID: 40348682]

• Multidisciplinary team (hepatologist + surgeon + anaesthesiologist) is mandatory for pre-op assessment
• Correction of coagulopathy, thrombocytopenia and hepatic encephalopathy before elective surgery
• HVPG measurement helps stratify portal hypertension severity pre-operatively

8. MASLD/MASH in Pregnancy - FIGO 2025 Guidelines [PMID: 40299540]

• First international guideline specifically addressing liver disease in pregnancy
• MASLD in pregnancy is associated with gestational diabetes, pre-eclampsia, and preterm birth
• Liver function monitoring and metabolic optimization recommended in pregnant women with known CLD

9. ACLF (Acute-on-Chronic Liver Failure) - Evolving Definitions

• The 2024-2025 literature continued to debate EASL-CLIF vs APASL definitions of ACLF
• Key update: Bacterial infections and systemic inflammation (not just organ failures) are now recognized as the primary drivers of ACLF and its high short-term mortality
• MARS/SPAD (liver support devices) do not improve survival in ACLF - no longer recommended outside trials
• Granulocyte-colony stimulating factor (G-CSF) - benefit remains uncertain; conflicting RCT results; not standard practice in Western guidelines but still explored in Asian guidelines
• Early liver transplantation in ACLF (even without sobriety period in ALD-ACLF) - growing evidence supports this approach in selected patients

10. Hepatocellular Carcinoma (HCC) Surveillance

• Biannual ultrasound ± AFP remains standard in all cirrhotics and HBV patients with high-risk factors
• MASLD-cirrhosis now included as a formal indication for HCC surveillance (previously under-recognized)
• MRI-based surveillance (abbreviated MRI protocol) is emerging as superior to ultrasound in obese patients and MASLD - endorsed in some North American guidelines
• Alpha-fetoprotein-L3 and DCP (des-gamma-carboxyprothrombin) as adjunct biomarkers under evaluation

Summary Table of Key 2024-2026 Guideline Updates

1. MASLD/MASH has replaced NAFLD/NASH - and the first approved drug (resmetirom) has arrived
2. FIB-4 is the new gatekeeper for MASLD risk stratification before elastography or biopsy
3. Early TIPS within 72 hours is now the standard in high-risk acute variceal bleeds
4. HCC surveillance is now mandatory even after HCV cure in cirrhotic patients
5. Pre-emptive anticoagulation for portal vein thrombosis in cirrhosis has broader acceptance
6. Perioperative hepatology input is mandatory for any cirrhotic patient facing abdominal surgery