What are the management strategies for Chronic Liver Disease (CLD)?

Management of Chronic Liver Disease

The management of chronic liver disease requires identifying and treating the underlying etiology—whether viral hepatitis, alcohol-related, or metabolic dysfunction-associated steatotic liver disease (MASLD)—combined with surveillance for complications and hepatocellular carcinoma. 1, 2

Identify and Treat the Underlying Cause

The cornerstone of CLD management is targeting the specific etiology, which can potentially reverse early cirrhosis and prevent progression to end-stage liver disease 1, 2:

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

• Lifestyle modification is the primary intervention: achieve 7-10% weight loss through caloric restriction and regular physical activity, which improves liver histology, reduces inflammation, and can improve fibrosis 1, 2
• Exercise prescription: at least 150-300 minutes of moderate-intensity aerobic exercise per week 2
• Incretin-based therapies (semaglutide, tirzepatide) should be used for patients with type 2 diabetes or obesity with additional metabolic risk factors 1
• Resmetirom should be considered for adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) 1
• Bariatric surgery is an option for patients with MASLD and obesity 1

Viral Hepatitis B

• For compensated cirrhosis with HBV DNA ≥2,000 IU/mL: initiate entecavir 0.5 mg daily or tenofovir regardless of ALT levels 1, 2
• All patients with cirrhosis and detectable HBV DNA should receive treatment regardless of ALT levels 2
• Monitor HBV DNA and ALT every 3-6 months during therapy 2

Viral Hepatitis C

• Direct-acting antivirals (DAAs) can improve liver function and reduce portal hypertension with minimal side effects and high cure rates 1, 2
• 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 1, 2
• Avoid all alcohol intake, as even moderate consumption accelerates disease progression 1

Screening and Case-Finding

Apply case-finding strategies using non-invasive tests (FIB-4 score followed by transient elastography) in individuals with cardiometabolic risk factors, abnormal liver enzymes, or radiological signs of hepatic steatosis 1:

• FibroScan <10 kPa rules out compensated advanced chronic liver disease (cACLD) 3
• FibroScan ≥15 kPa is highly suggestive of cACLD 3
• FibroScan 10-15 kPa (gray zone): use platelet count to help stratify—FibroScan <15 kPa with platelets >150,000 can rule out cACLD 3

Management of Cirrhosis Complications

Ascites

• First-line treatment: sodium restriction (88 mmol/day or 2 grams/day) and spironolactone 100 mg daily, with or without furosemide 40 mg daily 1, 2
• Fluid restriction is not necessary unless serum sodium is <120-125 mmol/L 1
• For tense ascites: perform initial therapeutic paracentesis (removing 4-6 liters) followed by sodium restriction and diuretic therapy 1
• Avoid NSAIDs completely, as they reduce urinary sodium excretion and can convert diuretic-sensitive ascites to refractory ascites 1

Variceal Bleeding

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

Hepatic Encephalopathy

• Lactulose is first-line therapy, reducing mortality (8.5% vs 14%) and recurrent overt hepatic encephalopathy (25.5% vs 46.8%) 1
• Identify and treat precipitating factors: infection, GI bleeding, constipation, electrolyte abnormalities, and medications 1
• Ensure adequate protein intake (1.2-1.5 g/kg/day) to prevent sarcopenia, which worsens hepatic encephalopathy 1

Surveillance and Monitoring

Hepatocellular Carcinoma Surveillance

• Perform ultrasound with or without alpha-fetoprotein every 6 months in all patients with cirrhosis 1, 2
• Continue surveillance even after achieving sustained virologic response (SVR) in viral hepatitis, as HCC risk persists 1, 2

Variceal Screening

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

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

Post-Viral Clearance Monitoring

• All patients with previous HCV (HCV antibody-positive, HCV RNA-negative) or resolved HBV (HBsAg-negative, HBcAb-positive) should be screened for additional factors of chronic liver damage and evaluated for signs of advanced chronic liver disease even if asymptomatic 3
• Patients with previous diagnosis of advanced fibrosis/cirrhosis should continue with hepatological follow-up despite successful antiviral therapy 3

Nutritional and Bone Health Management

Nutritional Support

• Vitamin D supplementation is recommended for levels below 20 ng/ml to achieve levels above 30 ng/ml 2
• Calcium (1,000-1,500 mg/day) and vitamin D (400-800 IU/day) supplementation for all patients with chronic liver disease 3, 2
• Vitamin K supplementation should be considered in patients with jaundice or cholestatic liver disease 2

Bone Disease Management

• Bone densitometry should be evaluated in patients with previous fragility fractures, those treated with corticosteroids, and before liver transplantation 3, 2
• Bisphosphonates may be considered for patients with established osteoporosis, particularly those with primary biliary cholangitis 2
• Repeat DEXA after 2-3 years in patients with normal BMD; in conditions with rapid bone loss (cholestatic patients, high-dose corticosteroids), repeat in approximately one year 3

Patient Education

Educate patients about salt restriction (2 grams/day), medication adherence, and recognition of warning signs (confusion, abdominal distension, black stools, jaundice) 1:

• Provide written materials and involve caregivers in education sessions 1
• Consider telemedicine and remote monitoring technologies to improve outcomes and reduce hospital readmissions 1

Liver Transplantation Referral

Patients with cirrhosis should be referred for transplantation when they develop evidence of hepatic dysfunction or when they experience their first major complication 2:

• Patients with type I hepatorenal syndrome should have expedited referral for liver transplantation 2