What is the treatment for liver cirrhosis in an adult with a history of liver disease or risk factors?

MASH Cirrhosis: Treatment and Management

Understanding MASH Cirrhosis

MASH (Metabolic dysfunction-Associated Steatohepatitis) cirrhosis represents the end-stage of metabolic liver disease and requires aggressive treatment of the underlying metabolic dysfunction combined with comprehensive management of cirrhosis complications to prevent decompensation and improve survival. 1

MASH cirrhosis develops from chronic metabolic dysfunction including insulin resistance, obesity, hypertension, and dyslipidemia, with evidence showing that the risk of developing hepatocellular carcinoma in MASH-related cirrhosis (18-27%) may exceed that of hepatitis C-related cirrhosis. 1

Primary Treatment Strategy: Address the Underlying Cause

The cornerstone of managing MASH cirrhosis is aggressive treatment of metabolic dysfunction, which can potentially reverse early cirrhosis, prevent decompensation, and improve survival. 2

Weight Loss and Lifestyle Modification

• Moderate weight reduction with emphasis on high protein intake (1.2-1.5 g/kg/day) and physical activity is essential to maintain muscle mass and reduce sarcopenia risk in compensated MASH cirrhosis. 1
• Dietary sodium restriction to less than 5 g/day (2000 mg/day) is mandatory for ascites control, though greater restriction may worsen malnutrition. 2, 3
• Total caloric intake should be 35-40 kcal/kg/day with carbohydrate intake of 2-3 g/kg/day. 1
• A late-evening snack is recommended to prevent muscle catabolism, particularly in patients with sarcopenia or decompensated disease. 1

Bariatric Surgery Considerations

• In adults with non-cirrhotic MASH who have an approved indication, bariatric surgery should be considered because it induces long-term beneficial effects on the liver and is associated with remission of type 2 diabetes. 1
• In adults with MASH-related compensated advanced chronic liver disease/compensated cirrhosis who have an approved indication, bariatric surgery can be considered but requires careful evaluation by a multidisciplinary team with experience in this population, particularly assessing for clinically significant portal hypertension. 1

Pharmacological Management of Comorbidities

Diabetes Management

For compensated MASH cirrhosis (Child-Pugh A):

• GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) or coagonists (tirzepatide) are first-line agents for type 2 diabetes. 1
• SGLT2 inhibitors (empagliflozin, dapagliflozin) can be used in Child-Pugh class A and B cirrhosis. 1
• Metformin can be used in compensated cirrhosis with preserved renal function (glomerular filtration rate >30 mL/min) but is absolutely contraindicated in decompensated cirrhosis due to lactic acidosis risk. 1, 3

For decompensated MASH cirrhosis:

• Insulin therapy is the only evidence-based option for treating type 2 diabetes in decompensated cirrhosis. 2
• HbA1c should not be used for diagnosis or monitoring glycemic control in decompensated cirrhosis. 2
• Sulfonylureas should be avoided due to hypoglycemia risk. 1

Lipid Management

• Statins can and should be used in adults with MASH cirrhosis, including those with compensated cirrhosis, according to cardiovascular risk guidelines to reduce cardiovascular events. 1
• Statins show promise in reducing portal hypertension and improving survival in advanced cirrhosis. 2

MASH-Targeted Therapy

• If locally approved, resmetirom should be considered in patients with F2/F3 fibrosis (non-cirrhotic MASH). 1

Management of Cirrhosis Complications

Ascites Management

Grade 1 ascites (mild):

• Sodium restriction, treatment of underlying metabolic disease, nutritional education, and discontinuation of NSAIDs, ACE inhibitors, or angiotensin receptor blockers. 2

Grade 2 ascites (moderate):

• Sodium restriction plus oral diuretics starting with spironolactone 50-100 mg/day (maximum 400 mg/day) with or without furosemide 20-40 mg/day (maximum 160 mg/day). 2

Grade 3 ascites (tense):

• Therapeutic paracentesis first, followed by sodium restriction and diuretic therapy. 2, 3
• Large-volume paracentesis with albumin replacement is recommended for refractory ascites. 4

Prevention of Variceal Bleeding

• Non-selective beta-blockers (carvedilol or propranolol) should be used to reduce risk of variceal bleeding, ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, and hepatic encephalopathy in responders who achieve marked portal pressure reduction. 2, 5
• Use with caution in patients with severe or refractory ascites. 2

Hepatic Encephalopathy

• Lactulose or lactitol is first-line therapy for hepatic encephalopathy management. 3, 5
• Rifaximin may be considered to reduce risk of multiple complications. 3

Hepatocellular Carcinoma Surveillance

• Six-monthly abdominal ultrasound assessments in combination with serum AFP estimation should be performed for HCC surveillance in all patients with MASH cirrhosis. 1
• Mandatory lifelong screening for HCC is required, even if recompensation occurs. 3
• The annual incidence of HCC in MASH cirrhosis is 1-4%. 5

Critical Medications to Avoid

NSAIDs are absolutely contraindicated in MASH cirrhosis because they reduce urinary sodium excretion, precipitate renal dysfunction, and convert diuretic-sensitive ascites to refractory ascites. 2, 3

Additional contraindications include:

• ACE inhibitors and angiotensin receptor blockers 2, 3
• Nephrotoxic drugs 3
• Beta-blockers during acute bleeding 3
• Metformin in decompensated cirrhosis 1, 3

Nutritional Assessment and Sarcopenia Management

• Rapid nutritional screening should be performed in all patients, assuming high risk for malnutrition if BMI <18.5 kg/m² or Child-Pugh C. 2, 3
• Sarcopenia assessment using CT scan, anthropometry, DEXA, or BIA is essential. 2, 3
• Muscle function should be evaluated with handgrip strength and/or short physical performance battery. 2, 3
• Bed rest is not recommended as excessive bed rest causes muscle atrophy; patients can be managed outpatient unless complicated by bleeding, encephalopathy, infection, hypotension, or liver cancer. 2

Monitoring and Follow-up

• Clinical assessment with laboratory tests and calculation of Child-Pugh and MELD scores should occur every 6 months. 6
• Diagnostic paracentesis should be performed without delay in all cirrhotic patients with ascites on hospital admission to rule out spontaneous bacterial peritonitis. 2, 3
• Renal function monitoring is critical before and during therapy. 3

Liver Transplantation Evaluation

• Evaluation for liver transplantation is indicated for patients with MELD score ≥15, complications of cirrhosis, or hepatocellular carcinoma. 6
• Liver transplantation is potentially optimal therapy for small-size hepatocellular carcinoma in patients with moderate to severe cirrhosis (Child-Pugh class B or C). 4
• Patients should be referred immediately for transplant evaluation when decompensation occurs, as early referral improves outcomes. 3
• Mean pulmonary arterial pressure ≥45 mmHg is an absolute contraindication. 3

Common Pitfalls

• Patients requiring paracenteses more frequently than every 2 weeks likely have poor dietary compliance rather than true refractory ascites. 2
• Greater dietary sodium restriction beyond 5 g/day may worsen malnutrition and should be avoided. 2
• Surgery in patients with underlying cirrhosis carries substantial morbidity and mortality (30-50% in Child-Pugh class B or C, but only 5-10% in Child-Pugh class A). 4
• Only 10-30% of patients initially presenting with HCC will be eligible for surgery. 4