What is the recommended treatment for chronic Hepatitis B?

Treatment of Chronic Hepatitis B

First-line treatment for chronic hepatitis B should be entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide due to their high potency and high genetic barrier to resistance. 1

Patient Selection for Treatment

Treatment decisions should be based on:

1. HBeAg status
2. HBV DNA levels
3. ALT/AST levels
4. Presence of cirrhosis
5. Age and comorbidities

Treatment is indicated for:

• HBeAg-positive patients:

  • HBV DNA >20,000 IU/mL AND ALT >2× ULN 2, 1
  • OR significant inflammation/fibrosis on biopsy 2

• HBeAg-negative patients:

  • HBV DNA >2,000 IU/mL AND ALT >2× ULN 2, 1
  • OR significant inflammation/fibrosis on biopsy 2

• Cirrhotic patients:

  • Any detectable HBV DNA regardless of ALT 1

• Special populations:

  • Patients >30 years with HBV DNA >20,000 IU/mL regardless of ALT 1

First-Line Treatment Options

Nucleos(t)ide Analogues (NAs)

1. High genetic barrier to resistance (preferred) 1:

   • Entecavir: 0.5 mg daily
   • Tenofovir disoproxil fumarate (TDF): 300 mg daily
   • Tenofovir alafenamide (TAF): 25 mg daily

2. Lower genetic barrier to resistance (not preferred as first-line) 2:

   • Lamivudine: 100 mg daily
   • Adefovir: 10 mg daily
   • Telbivudine

Pegylated Interferon

• Peginterferon alfa-2a: 180 μg weekly for 48 weeks 1
• Consider in young patients with high ALT, low HBV DNA, and without cirrhosis
• Advantages: finite treatment duration, no resistance
• Disadvantages: frequent side effects, contraindicated in decompensated cirrhosis 2

Treatment Duration

• HBeAg-positive patients: Minimum 1 year, continue 3-6 months after HBeAg seroconversion 2
• HBeAg-negative patients: Long-term/indefinite treatment (optimal duration not established) 2
• Cirrhotic patients: Long-term/indefinite treatment 2

Monitoring During Treatment

• ALT and HBV DNA every 3-6 months 1
• HBeAg/anti-HBe status every 6-12 months in HBeAg-positive patients 1
• Renal function monitoring, especially with tenofovir or adefovir 1, 3
• HCC surveillance with ultrasound every 6 months in high-risk patients 1

Management of Antiviral Resistance

Resistance is defined as:

• Virologic breakthrough: Increase in serum HBV DNA by ≥1 log10 above nadir while on treatment 2
• Genotypic resistance: Detection of mutations known to confer resistance 2

Management strategies:

1. Lamivudine resistance: Switch to tenofovir or add adefovir 2
2. Adefovir resistance: Switch to entecavir or add/switch to tenofovir 2
3. Multiple drug resistance: Combine tenofovir and entecavir 1 mg 2

Special Populations

Decompensated Cirrhosis

• Start entecavir or tenofovir immediately 2
• Avoid interferon due to risk of hepatic decompensation 2

Pregnancy

• Consider tenofovir in third trimester for women with high viral load to prevent vertical transmission 1

HIV Coinfection

• Use tenofovir-based regimen as part of HAART 1

Immunosuppression/Chemotherapy

• Prophylactic antiviral therapy (entecavir or tenofovir) should be started before immunosuppressive therapy and continued for at least 12 months after completion 1

Common Pitfalls to Avoid

1. Using lamivudine as first-line therapy - Despite lower cost, high resistance rates (up to 70% after 5 years) make it suboptimal 4

2. Premature discontinuation of therapy - Can lead to severe hepatitis flares 5

3. Inadequate monitoring - Failure to detect viral breakthrough early can lead to clinical deterioration and resistance 2

4. Overlooking renal toxicity - Particularly with adefovir and tenofovir 3

5. Failure to screen for HCC - Regular surveillance is essential in high-risk patients 1