What is the management approach for non-alcoholic cirrhosis?

Management of Non-Alcoholic Cirrhosis

Complete alcohol abstinence, specialized nutritional support with minimum 1.2-1.5 g/kg daily protein to prevent sarcopenia, gradual weight loss of LESS than 1 kg per week (never rapid weight loss as it can precipitate acute hepatic failure), GLP-1 receptor agonists or pioglitazone for diabetes, statins for dyslipidemia in compensated cirrhosis, and lifelong HCC surveillance with ultrasound every 6 months are the cornerstones of managing non-alcoholic cirrhosis. 1

Immediate Priorities

Transplant Evaluation

• Refer immediately for liver transplantation evaluation when the first major complication occurs or hepatic dysfunction develops 1
• Patients with hepatorenal syndrome type I require expedited transplant referral due to poor prognosis without transplantation 1
• Meticulous pretransplant cardiovascular evaluation is mandatory, as NASH patients experience high mortality from cardiovascular complications 1

Alcohol Elimination

• Complete alcohol abstinence is mandatory in NASH-cirrhosis to reduce hepatocellular carcinoma risk 1
• Even moderate daily alcohol use doubles the risk for adverse liver-related outcomes compared with lifetime abstainers 1

Nutritional Management (Critical in Cirrhosis)

Sarcopenia Prevention

• Sarcopenia occurs in 59% of patients with cirrhosis on transplant waiting lists, and NASH cirrhosis patients are 6 times more likely to have sarcopenic obesity 1
• Provide minimum protein intake of 1.2-1.5 g/kg daily with branched-chain amino acids from chicken, fish, eggs, nuts, lentils, and/or soy 2, 1
• Encourage frequent small meals and avoid more than 4-6 hours between meals 2
• Provide a bedtime snack containing protein and at least 50 g of complex carbohydrates 2
• Consultation with a specialized nutritionist is preferred given the complexity of nutritional needs 2

Exercise Prescription

• Moderate-intensity exercise for 150 minutes per week is beneficial 2
• Prescribe 150-300 minutes of moderate-intensity aerobic exercise weekly, or 75-150 minutes of vigorous-intensity exercise 1
• Walking more than 3 hours per week is associated with decreased cirrhosis-related deaths and HCC 1

Weight Management (Critical Distinction)

In compensated NASH cirrhosis, gradual weight loss of LESS than 1 kg per week is critical, as rapid weight loss can precipitate acute hepatic failure. 1

• Target 7-10% total body weight reduction to improve liver histology, but only with slow, controlled weight loss 1
• An individualized dietary plan should be devised to meet required caloric and nutritional requirements to avoid caloric deficits 2

Dietary Modifications

• Implement a Mediterranean diet pattern emphasizing vegetables, fruits, whole grains, legumes, and olive oil as the principal fat source 1
• Avoid fructose-containing beverages and foods 1
• Strictly limit red meat, processed meats, and ultra-processed foods 1

Pharmacological Management of Metabolic Comorbidities

Diabetes Management

• Prefer GLP-1 receptor agonists (liraglutide, semaglutide) or pioglitazone for diabetes in NASH patients, as these have proven efficacy on liver histology 2, 1
• GLP-1RAs appear safe overall but have not been widely tested in decompensated cirrhosis 2
• Pioglitazone is contraindicated in patients with decompensated cirrhosis 2, 1
• SGLT2 inhibitors (dapagliflozin, canagliflozin, empagliflozin) have reported approximately 20% placebo-subtracted reduction in steatosis by imaging, and are particularly beneficial for congestive heart failure or chronic kidney disease 2

Lipid Management

• Statins are safe and should be used to treat dyslipidemia in compensated cirrhosis (Child A or B) 2, 1
• Statin use in patients with cirrhosis is associated with 46% reduction in hepatic decompensation and 46% lower mortality 2
• Statins reduce HCC risk by 37% 1
• Statins should be avoided in Child class C cirrhosis 2, 1

HCC Surveillance (Lifelong Requirement)

• Perform right upper quadrant ultrasound with or without serum AFP every 6 months in patients with cirrhosis 1, 3, 4
• Use CT or MRI instead of ultrasound in overweight/obese patients where ultrasound quality is limited 1
• Lifelong HCC surveillance is required even after metabolic improvement 1

Pharmacotherapy for NASH

• No pharmacotherapy has been approved by regulatory agencies specifically for NAFLD treatment—all current options are off-label 1
• Consider vitamin E in patients with biopsy-confirmed NASH without diabetes or cirrhosis 1

Management of Cirrhosis Complications

Ascites

• Restrict sodium intake to 88 mmol/day 5
• Start spironolactone 100 mg once daily, add furosemide 40 mg once daily if needed 5
• Maximum doses: 400 mg/day spironolactone and 160 mg/day furosemide 5
• For tense ascites, perform large-volume paracentesis and administer intravenous albumin at 8g/L of fluid removed 5
• Fluid restriction only necessary if serum sodium <120-125 mmol/L 5

Hepatic Encephalopathy

• Identify and treat precipitants including constipation, infection, gastrointestinal bleeding, certain medications, and electrolyte imbalances 3
• Use lactulose or rifaximin to reduce serum ammonia levels 5, 3

Critical Pitfalls to Avoid

• Never pursue rapid weight loss—this can precipitate acute hepatic failure in advanced disease 1
• Avoid aggressive glycemic targets in advanced liver disease due to hypoglycemia risk 1
• Avoid NSAIDs as they reduce urinary sodium excretion and can convert diuretic-sensitive patients to refractory 5
• Avoid medications that worsen hypotension (ACE inhibitors) 5
• There is no safe threshold for alcohol intake in patients with advanced fibrosis 2