What is the recommended treatment for chronic hepatitis B?

Treatment of Chronic Hepatitis B

The recommended first-line treatment for chronic hepatitis B is a potent nucleos(t)ide analogue with high barrier to resistance, specifically entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide. 1

Patient Selection for Treatment

Treatment decisions should be based on:

1. HBV DNA levels:

   • HBeAg-positive: Treatment if HBV DNA >20,000 IU/mL
   • HBeAg-negative: Treatment if HBV DNA >2,000 IU/mL 1

2. ALT levels:

   • Treatment indicated if ALT >2× upper limit of normal (ULN) 1
   • If ALT persistently normal or minimally elevated (<2× ULN), treatment is generally not indicated 2

3. Liver histology:

   • Treatment indicated with moderate to severe necroinflammation on biopsy 2, 1

4. Cirrhosis status:

   • All patients with cirrhosis and detectable HBV DNA should be treated regardless of ALT levels 1

Preferred Treatment Options

First-line agents:

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

These agents are preferred due to their high barrier to resistance, potent viral suppression, and favorable safety profiles.

Alternative agents (not preferred due to resistance concerns):

• Lamivudine: 100 mg daily for adults
• Adefovir: 10 mg daily 2, 3

Treatment Algorithm Based on Patient Characteristics

1. HBeAg-positive chronic hepatitis B:

• If HBV DNA >20,000 IU/mL AND ALT >2× ULN:

  • Begin treatment with entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide
  • Minimum treatment duration: 1 year
  • Continue for 3-6 months after HBeAg seroconversion is confirmed 2, 1

• If HBV DNA >20,000 IU/mL but ALT <2× ULN:

  • Consider liver biopsy
  • Treat if moderate/severe necroinflammation is present 2

2. HBeAg-negative chronic hepatitis B:

• If HBV DNA >2,000 IU/mL AND ALT >2× ULN:
  • Begin treatment with entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide
  • Long-term or indefinite treatment is typically required 1

3. Cirrhotic patients:

• Compensated cirrhosis with detectable HBV DNA:

  • Treat with entecavir or tenofovir (avoid interferon due to risk of hepatic decompensation) 2, 1

• Decompensated cirrhosis:

  • Treat with entecavir or tenofovir
  • Coordinate treatment with transplant center
  • Interferon is contraindicated 2

Treatment Duration

• HBeAg-positive patients: Minimum 1 year, continue for 3-6 months after HBeAg seroconversion 2, 1
• HBeAg-negative patients: Long-term or indefinite treatment 1
• Cirrhotic patients: Long-term or indefinite treatment 1

Monitoring During Treatment

• Compliance: Assess at every visit
• Laboratory monitoring:
  • ALT and HBV DNA: Every 3-6 months
  • HBeAg/anti-HBe status: Every 6-12 months
  • Renal function: Every 6 months (especially with tenofovir) 1
• HCC surveillance: Ultrasound every 6 months for high-risk patients 1

Management of Treatment Failure

• Lamivudine resistance: Switch to or add adefovir 2
• Partial response: Consider switching to or adding a more potent agent 4

Important Cautions

• Never abruptly discontinue treatment due to risk of severe hepatitis flares 5
• Avoid interferon in decompensated cirrhosis due to risk of hepatic decompensation 2, 1
• Monitor renal function closely with adefovir or tenofovir 2
• Inactive HBsAg carriers (normal ALT, low HBV DNA) do not require treatment 2

By following this structured approach to treatment selection and monitoring, chronic hepatitis B can be effectively managed to prevent disease progression, reduce the risk of hepatocellular carcinoma, and improve long-term outcomes.