How should I manage a patient with chronic liver disease?

Management of Chronic Liver Disease

The management of chronic liver disease requires immediate identification and treatment of the underlying etiology—whether viral hepatitis, alcohol, metabolic dysfunction, or autoimmune disease—combined with systematic surveillance for complications and hepatocellular carcinoma, as removing the causative factor remains the only intervention proven to reverse early cirrhosis and prevent decompensation. 1, 2

Initial Diagnostic Workup and Etiology Identification

Mandatory Serologic Screening

• Test for HBsAg, anti-HBc, anti-HBs, anti-HCV, and HCV RNA to identify viral hepatitis as the underlying cause 2
• Check anti-HDV if HBsAg is positive to detect hepatitis D co-infection 2
• Obtain autoimmune panel including ANA, ASMA, anti-LKM, and quantitative immunoglobulins to detect autoimmune hepatitis 2
• Perform iron studies, ceruloplasmin with 24-hour urinary copper, and α-1 antitrypsin level to exclude hereditary metabolic diseases 2
• Verify anti-HAV status and vaccinate if seronegative 2

Assess Disease Severity

• Obtain comprehensive liver biochemistry: AST, ALT, GGT, alkaline phosphatase, bilirubin, albumin, and globulins 2
• Monitor platelet count trends, as progressive decline indicates evolving cirrhosis 2
• Check prothrombin time/INR to assess synthetic liver function 2
• Calculate AST/ALT ratio, as AST-dominant pattern (AST > ALT) suggests cirrhosis progression 2

Non-Invasive Fibrosis Assessment

• Begin with FIB-4 score; if elevated (≥1.30), proceed to transient elastography (FibroScan), ELF, or ARFI 2
• Liver stiffness ≤15 kPa with platelets ≥150 × 10⁹/L excludes clinically significant portal hypertension 2
• Liver stiffness ≥20 kPa or platelets <150 × 10⁹/L mandates upper endoscopy for variceal screening 2

Baseline Imaging

• Perform hepatic ultrasound to evaluate liver texture, nodularity, splenomegaly, and ascites 2
• Initiate 6-monthly contrast-enhanced CT or MRI for HCC surveillance in patients with cirrhosis or advanced fibrosis 2

Etiology-Specific Pharmacologic Management

Chronic Hepatitis B

• Initiate entecavir or tenofovir when HBV DNA ≥2,000 IU/mL with ALT elevation or any detectable HBV DNA in cirrhosis 1, 2
• Use WHO-standardized real-time PCR (IU/mL) to quantify HBV DNA for treatment decisions and monitoring 2
• Screen for HBsAg before corticosteroid or tocilizumab therapy and provide antiviral prophylaxis if positive to prevent reactivation 1
• Continue HCC surveillance indefinitely even after viral suppression 2, 3

Chronic Hepatitis C

• Treat with direct-acting antivirals to achieve sustained virological response, which reduces progression and decompensation 2, 3
• Continue HCC surveillance in cirrhotic patients despite SVR 2
• Quantify HCV RNA using the same assay consistently to evaluate treatment response 2

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

• Prescribe resmetirom for patients with stage F2-F3 fibrosis where approved 2
• Use GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) for concurrent type 2 diabetes 2
• Prescribe SGLT2 inhibitors (empagliflozin, dapagliflozin) for diabetes management 2
• Continue metformin in compensated cirrhosis with eGFR >30 mL/min/1.73 m², but avoid in decompensated disease 2
• Prescribe statins according to cardiovascular risk guidelines, as they are safe in compensated cirrhosis and reduce cardiovascular events 2
• Target 7-10% weight loss through caloric restriction and increased physical activity 1, 2

Alcohol-Related Liver Disease

• Mandate complete alcohol cessation, as this can lead to re-compensation and reversal of early cirrhosis 1
• Provide structured alcohol cessation programs and pharmacotherapy as needed 1

Autoimmune Hepatitis

• Initiate immunosuppression when diagnosis is confirmed, typically with prednisone with or without azathioprine 1

Management of Decompensation and Complications

Ascites

• Restrict sodium to 2 grams daily 1, 2
• Start spironolactone with or without furosemide as first-line diuretic therapy 1, 2
• Restrict fluids only if serum sodium falls below 120-125 mmol/L 1

Hepatic Encephalopathy

• Apply a four-pronged approach: assess consciousness level, exclude structural brain lesions (CT/MRI), identify and correct precipitants (infection, GI bleeding, constipation, medications), and start empirical therapy 2
• Prescribe lactulose as first-line treatment, titrating to 2-3 soft stools daily 2, 4
• Add rifaximin 550 mg twice daily as adjunct or alternative to lactulose 2, 4
• Periodically assess gait, cognition, and fall risk in patients with prior encephalopathy 2

Variceal Bleeding Prophylaxis

• Initiate non-selective beta-blockers in patients with clinically significant portal hypertension (LSM ≥20 kPa or platelets <150 × 10⁹/L) unless contraindicated 2
• Perform upper endoscopy for variceal screening when indicated by non-invasive criteria 2

Surveillance and Monitoring Strategy

HCC Surveillance

• Perform contrast-enhanced ultrasound, CT, or MRI every 6 months in cirrhotic patients 2
• Continue surveillance in chronic HBV carriers and HCV patients with F3 fibrosis even without cirrhosis 2

Disease Progression Monitoring

• Schedule regular outpatient follow-up to adjust therapy, monitor for decompensation, and manage precipitating factors 2
• Perform serial non-invasive fibrosis assessments to track disease regression or progression 2
• Use the same quantitative viral load assay consistently for monitoring antiviral efficacy 2

Preventive Care and Patient Education

Vaccination and Contact Screening

• Administer hepatitis A and B vaccines to seronegative individuals 2
• Test first-degree relatives and sexual partners of HBV-positive patients; vaccinate if non-immune 2

Patient and Family Education

• Counsel on medication adherence and expected benefits/adverse effects (e.g., lactulose-related diarrhea) 2
• Educate patients and families on early recognition of decompensation signs: ascites, encephalopathy, and gastrointestinal bleeding 2

Critical Safety Considerations and Medication Pitfalls

Medications to Avoid

• Discontinue all hepatotoxic agents, including over-the-counter and complementary products 2
• Avoid NSAIDs, as they precipitate renal dysfunction and exacerbate ascites 2
• Avoid sulfonylureas in decompensated cirrhosis due to severe hypoglycemia risk 2
• Avoid metformin in decompensated cirrhosis or eGFR <30 mL/min/1.73 m² to prevent lactic acidosis 2

Drug-Drug Interactions in COVID-19 Era

• Exercise caution with lopinavir-ritonavir, remdesivir, chloroquine, hydroxychloroquine, and tocilizumab in patients with chronic liver disease, as these agents carry hepatotoxicity risk 1
• Monitor ALT closely when these medications are necessary 1

Osteoporosis Prevention in Cholestatic Disease

• Supplement with calcium 1,000-1,200 mg/day and vitamin D 400-800 IU/day in patients with chronic cholestatic liver disease 1, 2
• Measure bone mineral density by DXA in patients with cirrhosis or severe cholestasis (bilirubin >3× ULN for >6 months) 1
• Administer parenteral vitamin K prophylactically before invasive procedures in overt cholestasis 2