What are the management strategies 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 underlying cause, which can potentially reverse early cirrhosis and prevent progression to end-stage liver disease. 1, 2, 3

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

• Lifestyle modification is the primary intervention, including weight loss, dietary changes, physical exercise, and discouraging alcohol consumption 1
• Incretin-based therapies (semaglutide, tirzepatide) should be used for patients with type 2 diabetes or obesity with additional metabolic risk factors 1
• Bariatric surgery is an option for patients with MASLD and obesity 1
• Resmetirom should be considered for adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2), as it demonstrates histological effectiveness on steatohepatitis and fibrosis 1
• Case-finding strategies using non-invasive tests (FIB-4 score followed by transient elastography) should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, or radiological signs of hepatic steatosis 1

Viral Hepatitis-Related Cirrhosis

• For hepatitis B with compensated cirrhosis: Initiate entecavir 0.5 mg daily or tenofovir when HBV DNA ≥2,000 IU/mL regardless of ALT levels 2, 4
• For lamivudine-refractory disease or decompensated cirrhosis: Use entecavir 1 mg daily 2, 4
• All patients with decompensated cirrhosis should receive treatment regardless of HBV DNA level 2
• Interferon-α is absolutely contraindicated in decompensated cirrhosis due to risk of serious complications including infection and hepatic failure 2
• For hepatitis C: Direct-acting antivirals (DAAs) can improve liver function and reduce portal hypertension, with minimal side effects and high cure rates 1, 3
• Monitor HCV RNA at weeks 4,8, and 12-24 of treatment depending on the regimen 1

Alcohol-Related Liver Disease

• Complete cessation of alcohol consumption is mandatory and may lead to "re-compensation" and improved outcomes 2, 3
• Avoid all alcohol intake, as even moderate consumption can accelerate disease progression 1

Management of Cirrhosis Complications

Ascites Management

• First-line treatment consists of sodium restriction (88 mmol/day or 2 grams/day) and diuretic therapy with spironolactone 100 mg daily, with or without furosemide 40 mg daily 2, 5
• Fluid restriction is not necessary unless serum sodium is less than 120-125 mmol/L 2
• For tense ascites, perform initial therapeutic paracentesis (removing 4-6 liters) followed by sodium restriction and diuretic therapy 2
• Combination aldosterone antagonist and loop diuretics are more effective than sequential initiation (76% vs 56% resolution rate) with lower rates of hyperkalemia (4% vs 18%) 5
• Avoid NSAIDs completely, as they reduce urinary sodium excretion and can convert diuretic-sensitive ascites to refractory ascites 2, 6

Refractory Ascites

• Options include serial large-volume paracentesis with albumin replacement, transjugular intrahepatic portosystemic shunt (TIPS), or liver transplantation 2, 3
• Patients requiring paracenteses more frequently than every 2 weeks likely have poor dietary compliance and need reinforced education 2
• Palliative care referral should be offered to patients with refractory ascites who are not transplant candidates 2
• Avoid propranolol in patients with refractory ascites, as it is associated with poorer outcomes 7

Variceal Bleeding Management

• Initiate vasoactive drugs (terlipressin, octreotide, or somatostatin) immediately upon suspicion, even before endoscopic confirmation 2
• Start antibiotic prophylaxis immediately in all cirrhotic patients with GI bleeding (ceftriaxone 1 gram daily for 7 days) 2
• Perform endoscopic band ligation within 12 hours of admission once hemodynamic stability is achieved 2
• Use a restrictive transfusion strategy with a hemoglobin threshold of 7 g/dL, targeting 7-9 g/dL 2
• TIPS should be used as rescue therapy for persistent bleeding or early rebleeding 2

Primary Prevention of Variceal Bleeding

• Non-selective β-blockers (carvedilol 6.25-12.5 mg daily or propranolol 20-40 mg twice daily) reduce the risk of decompensation or death (16% vs 27% over 3 years) 5
• Carvedilol reduces the rate of initial bleeding compared with band ligation 7
• Use with caution in patients with severe or refractory ascites 2

Hepatic Encephalopathy

• Lactulose is first-line therapy, reducing mortality (8.5% vs 14%) and recurrent overt hepatic encephalopathy (25.5% vs 46.8%) 1, 5
• Rifaximin 550 mg twice daily leads to better maintenance of remission and decreased readmission rates 7
• Identify and treat precipitating factors: infection, GI bleeding, constipation, electrolyte abnormalities, and medications 1, 2
• Ensure adequate protein intake (1.2-1.5 g/kg/day) to prevent sarcopenia, which worsens hepatic encephalopathy 1

Hepatorenal Syndrome

• Terlipressin improves the rate of reversal of hepatorenal syndrome from 18% to 39% 5
• Combination of terlipressin with albumin decreases mortality in patients with type 1 hepatorenal syndrome 7
• Avoid nephrotoxic drugs, large volume paracentesis without albumin replacement, and hypotensive drugs 2

Surveillance and Monitoring

Hepatocellular Carcinoma Screening

• Perform ultrasound with or without alpha-fetoprotein every 6 months in all patients with cirrhosis 1, 6
• Continue surveillance even after achieving sustained virologic response (SVR) in viral hepatitis, as HCC risk persists 1

Portal Hypertension Monitoring

• Screen for varices by endoscopy at the time of cirrhosis diagnosis 2, 6
• Repeat endoscopy every 1-3 years depending on the size of varices and degree of liver dysfunction 2

Fibrosis Reassessment

• Reassess fibrosis using non-invasive tests after 3 years in patients who remain at risk 1
• Extend the interval to 5 years in patients with no risk factors for progression who achieve weight loss goals 1

Specific Medication Adjustments

Renal Impairment

• For entecavir dosing with creatinine clearance 30-50 mL/min: 0.5 mg every 48 hours (usual dose) or 0.5 mg once daily (lamivudine-refractory or decompensated) 4
• For creatinine clearance 10-30 mL/min: 0.5 mg every 72 hours (usual dose) or 1 mg every 72 hours (lamivudine-refractory or decompensated) 4
• For creatinine clearance <10 mL/min or hemodialysis: 0.5 mg every 7 days (usual dose) or 1 mg every 7 days (lamivudine-refractory or decompensated) 4

Monitoring After Treatment Discontinuation

• Monitor hepatic function closely with clinical and laboratory follow-up for at least several months after discontinuing anti-hepatitis B therapy, as severe acute exacerbations can occur 4
• Reinitiate anti-hepatitis B therapy if appropriate based on clinical and laboratory findings 4

Referral to Gastroenterology/Hepatology

Refer immediately when patients develop any decompensation event (ascites, variceal bleeding, hepatic encephalopathy), refractory ascites not responding to maximum diuretic therapy, or need evaluation for TIPS or liver transplantation 2

Patient Education and Support

• Educate patients about salt restriction (2 grams/day), medication adherence, and recognition of warning signs (confusion, abdominal distension, black stools, jaundice) 2, 3
• Provide written materials and involve caregivers in education sessions 1
• Consider telemedicine and remote monitoring technologies to improve outcomes and reduce hospital readmissions 1, 3

Common Pitfalls to Avoid

• Never use NSAIDs in patients with cirrhosis, as they precipitate renal failure and worsen ascites 2, 6
• Do not restrict protein intake in hepatic encephalopathy, as this worsens sarcopenia and outcomes 1
• Avoid interferon-based therapies in decompensated cirrhosis, as they can cause fatal hepatic failure 2
• Do not use propranolol in patients with refractory ascites, as it worsens survival 7
• Always test for HIV before initiating entecavir, as monotherapy can lead to HIV resistance 4