What are the guidelines for treating common liver illnesses, such as hepatitis B (HBV) and hepatitis C (HCV), and cirrhosis?

Guidelines for Treating Common Liver Illnesses: Hepatitis B, Hepatitis C, and Cirrhosis

The treatment of common liver illnesses such as hepatitis B, hepatitis C, and cirrhosis should follow evidence-based guidelines with nucleos(t)ide analogues (NAs) with high genetic barrier to resistance being the first-line treatment for hepatitis B, direct-acting antivirals for hepatitis C, and specific management strategies for cirrhosis based on etiology and severity.

Hepatitis B (HBV) Management

Treatment Indications

Treatment decisions for chronic HBV infection are based on:

• HBV DNA levels
• ALT levels
• Severity of liver disease

When to Start Treatment

1. Immediate treatment required for:

   • Decompensated cirrhosis with any detectable HBV DNA 1
   • Compensated cirrhosis with detectable HBV DNA (regardless of ALT) 1, 2
   • Severe HBV reactivation 1
   • Liver failure 2

2. Treatment recommended for:

   • HBeAg-positive patients with HBV DNA ≥20,000 IU/mL AND ALT ≥2× ULN 1, 2
   • HBeAg-negative patients with HBV DNA ≥2,000 IU/mL AND ALT ≥2× ULN 1, 2
   • Patients with HBV DNA >2,000 IU/mL, ALT >ULN, AND moderate liver necroinflammation or significant fibrosis (≥A2 or ≥F2) 1, 2

3. Consider liver biopsy before treatment for:

   • Patients with ALT 1-2× ULN and treat if moderate-to-severe necroinflammation or significant fibrosis 1
   • HBeAg-positive patients >30-40 years with normal ALT but high HBV DNA 1

First-Line Antiviral Agents

High genetic barrier nucleos(t)ide analogues are recommended as first-line therapy 1, 2:

• Entecavir (0.5 mg daily)
• Tenofovir disoproxil fumarate (300 mg daily)
• Tenofovir alafenamide (25 mg daily)
• Besifovir

Treatment Duration

• HBeAg-positive patients: Continue treatment for at least 6 months after HBeAg seroconversion 2
• HBeAg-negative patients: Long-term treatment typically required (80-90% relapse if stopped within 1-2 years) 2

Monitoring During Treatment

• HBV DNA levels: Every 3-6 months 2
• ALT/AST: Every 3-6 months 2
• HBeAg/anti-HBe (in HBeAg-positive patients): Every 6-12 months 2
• Renal function: Every 6-12 months (especially with tenofovir) 2
• Non-invasive fibrosis assessment: Annually 2

Managing Resistance

• Viral resistance to lamivudine: Up to 70% in 5 years 2
• Lower resistance with entecavir (<1% at 4 years) 2
• For resistance: Switch to or add a high-genetic-barrier drug (entecavir or tenofovir) 2

Hepatitis C (HCV) Management

Pre-Treatment Assessment

• Confirm active HCV infection with HCV RNA quantification 1
• Determine HCV genotype and subtype (particularly 1a/1b) 1
• Assess liver disease severity (fibrosis stage) 1
• Screen for HBV and HIV coinfection 1

Treatment Indications

Direct-acting antiviral (DAA) therapy is indicated for all patients with chronic HCV infection, with priority for:

• Patients with significant fibrosis or cirrhosis (METAVIR F2, F3, or F4) 1
• Patients with clinically significant extrahepatic manifestations 1
• Patients with HCV recurrence after liver transplantation 1

Treatment Regimens

Current standard of care is interferon-free DAA regimens based on:

• HCV genotype
• Prior treatment experience
• Presence of cirrhosis
• Presence of decompensation

For genotype 1 HCV:

• Ledipasvir/sofosbuvir for 12 weeks (8 weeks in treatment-naïve non-cirrhotic patients with low viral load) 3
• Sofosbuvir/velpatasvir for 12 weeks 1
• Glecaprevir/pibrentasvir for 8-12 weeks

Special Populations

• Decompensated cirrhosis: IFN-free regimens (e.g., sofosbuvir/ledipasvir + ribavirin) 1, 3
• Post-liver transplant: DAA therapy with ribavirin (e.g., ledipasvir/sofosbuvir + ribavirin) 3
• Renal impairment: Dose-adjusted regimens or specific DAA combinations 3

Cirrhosis Management

Assessment and Monitoring

• Determine etiology (viral, alcoholic, NAFLD, autoimmune, etc.)
• Assess severity: Child-Pugh score, MELD score
• Screen for complications:
  • Varices (endoscopy)
  • Hepatocellular carcinoma (ultrasound every 6 months)
  • Ascites, encephalopathy

Management Based on Etiology

HBV-related Cirrhosis

• Compensated: Treat with high genetic barrier NAs (entecavir or tenofovir) 1, 2
• Decompensated: Urgent antiviral therapy with NAs; consider liver transplantation evaluation 1, 4

HCV-related Cirrhosis

• Compensated: DAA therapy based on genotype 1
• Decompensated: IFN-free regimens; consider liver transplantation evaluation 1

Management of Complications

• Ascites: Sodium restriction, diuretics, paracentesis
• Spontaneous bacterial peritonitis: Antibiotics, prophylaxis in high-risk patients
• Variceal bleeding: Endoscopic band ligation, beta-blockers, TIPS
• Hepatic encephalopathy: Lactulose, rifaximin, identify and treat precipitating factors

Important Clinical Considerations

1. Regression of cirrhosis is possible with sustained viral suppression in both HBV and HCV, seen in 64-70% of patients with effective antiviral therapy 5

2. Risk factors for progression to cirrhosis in chronic HBV include:

   • Older age (>45 years)
   • Male gender
   • Persistent hepatitis (elevated ALT >1.5× ULN for >1 year)
   • Diabetes mellitus 6

3. Coexisting liver disorders should be considered in patients who don't respond to antiviral therapy, particularly NAFLD 4

4. Liver transplantation should be considered early for patients with decompensated cirrhosis who may not improve with antiviral therapy 1, 4

5. Prevention strategies include:

   • HBV vaccination for contacts of infected individuals 1
   • HAV vaccination for HBV/HCV-infected patients 1
   • Alcohol abstinence 2
   • Metabolic risk factor management