What is the recommended treatment for Hepatitis B (HBV)?

Treatment of Hepatitis B (HBV)

The recommended first-line treatments for chronic hepatitis B are entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide, which have high genetic barriers to resistance and should be selected based on the patient's clinical status, HBV DNA levels, and liver disease severity. 1

Patient Assessment and Treatment Criteria

Treatment decisions should be based on:

• HBV DNA levels
• ALT/AST levels
• HBeAg status
• Presence of cirrhosis
• Age and comorbidities

Treatment Indications:

• HBeAg-positive patients:

  • HBV DNA >20,000 IU/mL and ALT >2× upper limit of normal (ULN) 1, 2
  • Patients >30 years old with HBV DNA >20,000 IU/mL regardless of ALT 2

• HBeAg-negative patients:

  • HBV DNA >2,000 IU/mL and ALT >ULN 1, 2
  • HBV DNA >2,000 IU/mL with significant liver inflammation/fibrosis on biopsy 1

• Cirrhotic patients:

  • Compensated cirrhosis: HBV DNA ≥2,000 IU/mL regardless of ALT 1, 2
  • Decompensated cirrhosis: Treat regardless of HBV DNA or ALT levels 1

Treatment Options

First-Line Agents:

1. Nucleos(t)ide Analogues:

   • Entecavir: 0.5 mg daily 1
   • Tenofovir disoproxil fumarate: 300 mg daily 1
   • Tenofovir alafenamide: 25 mg daily 1

2. Pegylated Interferon alfa-2a:

   • 180 μg weekly for 48 weeks 1
   • Best for young patients with high ALT, low HBV DNA, and without cirrhosis 1
   • Limited by side effects and subcutaneous administration 3

Older Agents (Not First-Line):

1. Lamivudine:

   • Adult dose: 100 mg daily 4
   • Higher risk of resistance development with long-term use 1

2. Adefovir:

   • Adult dose: 10 mg daily 4, 5
   • Slower action and potential nephrotoxicity 1
   • Requires dose adjustment in renal impairment 5

Special Populations

Patients with Cirrhosis:

• Compensated cirrhosis: Oral antivirals preferred over interferon due to risk of hepatic decompensation 4
• Decompensated cirrhosis: Lamivudine or adefovir recommended; interferon contraindicated 4

Patients Requiring Immunosuppression:

• Prophylactic antiviral therapy recommended at onset of chemotherapy or immunosuppressive therapy 4
• Continue for 6 months after completion of immunosuppressive therapy 4
• For patients with high pre-chemotherapy DNA levels (>2,000 IU/mL), continue until reaching therapeutic endpoints for chronic hepatitis B 4
• Lamivudine or entecavir preferred due to rapid onset of action and lack of nephrotoxicity 4

Patients with Acute Symptomatic Hepatitis B:

• Treatment indicated only for fulminant hepatitis B or protracted, severe acute hepatitis B 4
• Lamivudine, telbivudine, or entecavir preferred 4

Treatment Duration

• HBeAg-positive patients: Minimum 1 year; continue 3-6 months after HBeAg seroconversion 4, 1
• HBeAg-negative patients: Longer than 1 year; often indefinite due to high relapse rates (80-90%) 4, 1
• Cirrhotic patients: Long-term (indefinite) treatment regardless of HBeAg status 1

Monitoring During Treatment

• ALT and HBV DNA every 3-6 months
• HBeAg/anti-HBe status every 6-12 months
• Renal function monitoring, especially with adefovir 5
• Ultrasound for HCC surveillance every 6 months 1

Management of Resistance

• For lamivudine-resistant mutants, use adefovir 4
• Consider combination therapy for difficult-to-treat cases 1
• For all patients, consider modifying treatment if serum HBV DNA remains above 1000 copies/mL with continued treatment 5

Important Warnings

• Severe acute exacerbations may occur upon discontinuation of therapy; monitor hepatic function closely 5, 6
• Nephrotoxicity risk with adefovir; monitor renal function 5
• Lactic acidosis and severe hepatomegaly with steatosis have been reported; suspend treatment if suspected 5, 6

The landscape of HBV treatment continues to evolve, with newer agents showing improved efficacy and safety profiles compared to older medications like lamivudine and adefovir.