What are the management options for chronic liver disease?

Management of Chronic Liver Disease

Treat the Underlying Etiology First

The cornerstone of chronic liver disease management is identifying and treating the specific underlying cause, as this prevents progression to cirrhosis and hepatocellular carcinoma. 1, 2

Viral Hepatitis Management

• For chronic hepatitis B, use first-line agents entecavir, tenofovir, or peginterferon alfa-2a in patients with elevated ALT and HBV DNA ≥2000 IU/mL 1
• All cirrhotic patients with detectable HBV DNA require treatment regardless of ALT levels 1
• Monitor HBV DNA and ALT every 3-6 months during therapy, and assess for virologic breakthrough and renal function in patients on nucleos(t)ide analogues 1
• For chronic hepatitis C, direct-acting antivirals (DAAs) achieve high cure rates and should be used in all eligible patients 1
• Sustained viral suppression for HBV and sustained viral response for HCV prevent cirrhosis progression and reduce (but do not eliminate) HCC risk 2

Alcohol-Related Liver Disease

• Complete and permanent alcohol abstinence is mandatory for all patients with alcoholic liver disease 1, 2
• Heavy drinking is defined as >4 drinks/day or >14 drinks/week in men, and >3 drinks/day or >7 drinks/week in women—these thresholds must not be exceeded 2
• Provide parenteral thiamine 100 mg plus other vitamin and mineral supplementation as needed 3

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD/NAFLD)

Lifestyle modification is the primary treatment for MASLD, with weight loss of 7-10% required to improve steatohepatitis and achieve fibrosis regression. 4, 1, 5

Weight Loss Strategy

• Achieve 5% weight loss to improve steatosis alone; 7-10% weight loss is necessary for fibrosis regression 5
• Create a 500-1000 kcal/day deficit: typically 1,200-1,500 kcal/day for women and 1,500-1,800 kcal/day for men 5
• Weight loss must be gradual at 500-1000g per week maximum, as rapid weight loss worsens liver disease 5

Dietary Modifications

• Implement a Mediterranean diet pattern with daily vegetables, fruits, fiber-rich cereals, nuts, fish or white meat, and olive oil—this reduces liver fat even without weight loss 4, 5
• Eliminate fructose-containing beverages and processed foods 5
• Replace saturated fats with monounsaturated and polyunsaturated fats, especially omega-3 fatty acids 5

Exercise Requirements

• Prescribe 150-300 minutes of moderate-intensity aerobic exercise per week or 75-150 minutes of vigorous-intensity exercise 4, 5
• Both aerobic and resistance training reduce liver fat, with vigorous exercise providing greater benefit for NASH and fibrosis than moderate exercise 5

Pharmacological Options for MASLD

• For non-cirrhotic MASH with significant fibrosis (stage ≥2), consider resmetirom if locally approved, which demonstrates histological effectiveness on steatohepatitis and fibrosis 4
• Use incretin-based therapies (semaglutide, tirzepatide) for patients with type 2 diabetes or obesity when indicated 4
• GLP-1 agonists are effective for NASH recovery; avoid sulfonylureas and insulin as they may increase HCC risk 5
• Bariatric surgery is an option for patients with MASLD and obesity meeting national eligibility criteria—it resolves NASH in 85% of patients at 1 year and improves steatosis, steatohepatitis, and fibrosis 4, 5
• No MASH-targeted pharmacotherapy is currently recommended for the cirrhotic stage 4

Risk Stratification and Surveillance

Fibrosis Assessment Strategy

Use a stepwise approach with FIB-4 score followed by transient elastography to identify patients with advanced fibrosis who require closer monitoring. 4

• Apply case-finding strategies in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological hepatic steatosis, particularly with type 2 diabetes or obesity with additional metabolic risk factors 4
• Use blood-based scores (FIB-4) first, then imaging techniques (transient elastography) sequentially to rule-out/in advanced fibrosis 4
• Manage low-risk patients in the community with lifestyle advice and cardiovascular risk reduction, reassessing with non-invasive tests after 3 years 4
• Fibrosis progresses in a significant proportion of individuals, so repeated assessment every 1-3 years is required in at-risk patients 4

Hepatocellular Carcinoma Surveillance

• Perform 6-monthly ultrasound and AFP measurement for all cirrhotic patients 2
• Lifelong HCC surveillance is required for cirrhotic patients, even after viral clearance 1
• Early treatment of underlying liver diseases before progression to cirrhosis is the most effective approach for preventing HCC and liver-related mortality 1

Vaccination and Prevention

• Vaccinate against hepatitis B: all infants (universal childhood immunization), high-risk adults, and exposed individuals 2
• Vaccinate against hepatitis A: all anti-HAV negative patients with chronic liver disease 2
• Hepatitis B vaccination reduces HCC risk and is recommended for all newborns and high-risk groups 1

Management of Cardiometabolic Comorbidities

Cardiovascular disease is the main driver of morbidity and mortality in NAFLD patients before cirrhosis develops, requiring aggressive management of all metabolic risk factors. 5

• Use statins for dyslipidemia in all NAFLD patients—they carry no increased risk of serious liver injury and reduce HCC risk by 37% 5
• Optimize treatment for type 2 diabetes, as patients with or who develop T2DM have higher risk of fibrosis progression 4
• Assess lipid profile, fasting glucose/HbA1c, waist circumference, and BMI regularly 5

Nutritional and Bone Health Management

Vitamin and Mineral Supplementation

• Correct vitamin D insufficiency with 800 IU of vitamin D₃ and 1 g of calcium daily 4, 2
• Vitamin D deficiency is common and correlates with disease severity; supplement for levels below 20 ng/ml to achieve levels above 30 ng/ml 1
• Consider vitamin K supplementation in patients with jaundice or cholestatic liver disease 1
• Water-soluble vitamin deficiencies may develop rapidly; multivitamin supplementation is reasonable in decompensated patients 1

Bone Disease Management

• Evaluate bone densitometry in patients with previous fragility fractures, those treated with corticosteroids, and before liver transplantation 1
• All patients with cirrhosis or severe cholestasis (bilirubin >3× upper limit for >6 months) require bone density assessment 2
• Provide calcium supplementation (1-1.2 g/day) plus vitamin D₃ (400-800 IU/day) for all cholestatic patients 2
• Consider bisphosphonates for patients with established osteoporosis, particularly those with primary biliary cholangitis 1

Dietary Considerations

• Sodium intake should not be reduced below 60 mmol/day in patients with ascites 1
• Encourage coffee consumption—it decreases HCC risk in patients with chronic liver disease 2

Medication Safety

• Complete a blood aetiology screen and assess for additional causes of steatosis (drugs, alcohol) if not already done in primary care 4
• Document detailed alcohol history (using AUDIT-C), illicit drug use, and smoking history 4
• Review all medications for hepatotoxic potential, including amiodarone, anticonvulsants (carbamazepine, valproate), NSAIDs, glucocorticoids, methotrexate, tamoxifen, and antiretrovirals 4
• Avoid NSAIDs in chronic liver disease; acetaminophen below 2 g per day is the safest analgesic choice 6

Management of Cirrhosis and Complications

Cirrhotic Stage Considerations

• Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, and liver transplantation in decompensated cirrhosis 4
• Screen for gastroesophageal varices according to practice guidelines 1
• Refer patients for transplantation when they develop hepatic dysfunction or experience their first major complication 1
• Patients with type I hepatorenal syndrome should have expedited referral for liver transplantation 1

Special Populations

• HIV-HBV coinfection is associated with higher HBV DNA levels, more rapid progression to cirrhosis, and 14-fold higher liver-related mortality 1
• When steatosis and steatohepatitis are evident in patients with other types of chronic liver disease, assess for metabolic risk factors and alternate etiologies 1
• Patients with HCV-associated cirrhosis and HCC treated with curative intent maintain high HCC recurrence rates even after DAA therapy achieving sustained viral response 1

Common Pitfalls to Avoid

• Do not recommend weight loss faster than 500-1000g per week, as rapid weight loss can worsen liver disease 5
• Do not use sulfonylureas or insulin as first-line diabetes therapy in NAFLD patients due to increased HCC risk 5
• Do not assume viral clearance eliminates HCC risk—lifelong surveillance remains necessary 1
• Do not overlook cardiovascular risk in NAFLD patients, as cardiovascular disease causes more deaths than liver-related complications before cirrhosis develops 5
• Do not prescribe herbal remedies indiscriminately—many are hepatotoxic, though milk thistle can be used safely 6