What is the treatment for a patient with Metabolic Associated Steatohepatitis Liver Disease (MASLD)-related cirrhosis?

Treatment for MASLD-Related Cirrhosis

No MASH-targeted pharmacotherapy can currently be recommended for adults with MASH at the cirrhotic stage, and treatment must focus on lifestyle modification, management of cardiometabolic comorbidities, and surveillance for complications. 1

Core Management Strategy

The absence of approved liver-specific pharmacotherapy for cirrhotic MASLD requires a comprehensive approach targeting metabolic dysfunction and cirrhosis complications rather than hepatic inflammation directly 1, 2.

Lifestyle Modifications Adapted for Cirrhosis

Weight reduction targets differ critically from non-cirrhotic disease:

• Target 3-5% weight reduction (not the 7-10% used in non-cirrhotic MASH) to balance metabolic benefit against sarcopenia risk 1, 3
• High-protein diet is mandatory during any weight loss attempt to prevent muscle wasting 1, 3
• Late-evening snack (containing protein and complex carbohydrates) helps maintain nitrogen balance and prevent nocturnal muscle catabolism 1, 3
• Mediterranean dietary pattern with elimination of ultra-processed foods and sugar-sweetened beverages remains foundational 1
• Physical activity >150 minutes/week of moderate intensity should be maintained if functional status permits, with emphasis on resistance training to preserve muscle mass 1

Critical pitfall: Aggressive weight loss (>5%) in cirrhotic patients risks accelerating sarcopenia and hepatic decompensation 3.

Pharmacological Management of Metabolic Comorbidities

Since MASH-specific drugs are not recommended for cirrhosis, optimal treatment of diabetes, obesity, and cardiovascular disease becomes the primary pharmacological strategy 1, 2.

GLP-1 Receptor Agonists (Preferred First-Line)

• GLP-1 RAs (semaglutide, liraglutide) or dual GIP/GLP-1 agonists (tirzepatide) are safe in compensated cirrhosis and should be used for their approved indications of type 2 diabetes or obesity 1, 2, 4
• These agents improve cardiometabolic outcomes and may provide hepatic benefits through weight loss, though formal histological improvement has not been demonstrated in large Phase III trials for MASH 1, 4
• Contraindicated in Child-Pugh C cirrhosis; use cautiously in Child-Pugh B 4

SGLT2 Inhibitors

• Safe in MASLD and should be used for approved indications (diabetes, heart failure, chronic kidney disease) 1, 2
• Provide cardiovascular and renal protection, which is particularly relevant given the high cardiovascular mortality in MASLD 1, 2

Metformin

• Should be continued if already prescribed, as it is safe in compensated cirrhosis and may improve transplant-free survival 1, 2

Other Cardiometabolic Agents

• Statins, aspirin, and renin-angiotensin-aldosterone modulators may modify disease progression and reduce liver-related events 1, 3
• These should be used according to cardiovascular risk stratification 1

Surveillance and Complication Management

Portal hypertension screening:

• If liver stiffness measurement (LSM) ≥20 kPa and/or platelets <150×10⁹/L, perform upper gastrointestinal endoscopy to screen for varices 3
• If LSM ≤15 kPa plus platelets ≥150×10⁹/L, clinically significant portal hypertension is ruled out 3

Hepatocellular carcinoma surveillance:

• Ultrasound with or without AFP every 6 months is standard for all cirrhotic patients 1
• High FIB-4 (>2.67) at baseline and persistently elevated values are associated with >50-fold higher HCC risk 1

Decompensated Cirrhosis

When decompensation occurs:

• Liver transplantation evaluation should be initiated immediately 3
• High-protein diet with late-evening snack to address sarcopenia and nutritional deficiency 3
• Bariatric surgery is absolutely contraindicated in decompensated cirrhosis 3
• Pre-transplant weight optimization targets BMI <40 kg/m² (ideally <35 kg/m²) through dietary modification and supervised exercise 3

What NOT to Use

Resmetirom: Despite being the only FDA-approved MASH-targeted therapy, it is only recommended for non-cirrhotic MASH with significant fibrosis (F2-F3) and explicitly not for cirrhotic patients 1, 2

Vitamin E: Cannot be recommended as MASH-targeted therapy given lack of robust demonstration of histological efficacy in large Phase III trials and potential long-term risks 1

Saroglitazar: Not recommended as MASLD/MASH-targeted therapy due to lack of large Phase III trials demonstrating histological improvement 2, 4. May only be considered off-guideline when recommended therapies are unavailable, unaffordable, or contraindicated, with explicit patient counseling about lack of robust evidence 2

Multidisciplinary Approach

A multidisciplinary team is essential to address both hepatic and cardiometabolic components simultaneously 1, 3. This should include hepatology, endocrinology/diabetology, cardiology, nutrition, and physical therapy 1.

Monitoring Treatment Response

• Non-invasive tests (FIB-4, transient elastography) provide limited information about individual treatment response despite population-level utility 3
• Liver biopsy remains the gold standard for monitoring disease progression or treatment response, though not suited for routine practice 3
• Longitudinal changes in NITs can be informative but should not be the sole determinant of treatment efficacy 3

Future Directions

Development of effective pharmacological treatments for MASH-related cirrhosis remains a critical unmet need and research priority 1. Until such therapies emerge, the focus remains on metabolic optimization and complication prevention 2.