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

Treatment for Hepatitis B Infection

The first-line treatment for chronic hepatitis B infection is long-term administration of 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 patients: Treatment if HBV DNA >20,000 IU/mL
   • HBeAg-negative patients: Treatment if HBV DNA >2,000 IU/mL 1, 2

2. ALT levels:

   • Treatment recommended if ALT >2× upper limit of normal 2

3. Liver disease severity:

   • All cirrhotic patients with detectable HBV DNA should be treated regardless of ALT levels 1
   • Patients with at least moderate histological lesions should be treated 1, 3

First-Line Treatment Options

Nucleos(t)ide Analogues (NAs)

• Preferred agents (high barrier to resistance):
  • Entecavir: 0.5 mg daily
  • Tenofovir disoproxil fumarate: 300 mg daily
  • Tenofovir alafenamide: 25 mg daily 1, 2

Alternative Treatment

• Pegylated interferon alfa-2a: 180 μg weekly for 48 weeks
  • Consider for young patients with high ALT, low HBV DNA, without cirrhosis
  • Advantage: finite treatment duration
  • Disadvantage: frequent side effects 2

Not Recommended as Monotherapy

• Lamivudine, telbivudine, or emtricitabine due to high risk of resistance 1, 2
• Adefovir due to lower potency and risk of nephrotoxicity 4

Treatment Duration

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

Monitoring During Treatment

1. Compliance monitoring: At every visit 1

2. 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, 2

3. HCC surveillance:

   • Ultrasound every 6 months for high-risk patients (cirrhosis, family history of HCC, Asian men >40, Asian women >50) 2

Special Populations

Cirrhotic Patients

• All cirrhotic patients with detectable HBV DNA should be treated regardless of ALT levels 1
• Avoid interferon due to risk of hepatic decompensation 2

HBV/HIV Co-infection

• Use combination antiretroviral therapy including two drugs active against HBV (emtricitabine/tenofovir or lamivudine/tenofovir) 1, 2

Pregnant Women

• Consider tenofovir in third trimester if high viral load to prevent vertical transmission 2

Immunosuppressed Patients

• Antiviral prophylaxis (entecavir, tenofovir) before starting immunosuppressive therapy
• Continue for at least 12 months after completion of immunosuppressive treatment 2

Acute Hepatitis B

• Most patients (95-99%) recover spontaneously without antiviral therapy 1
• Consider NA treatment for severe acute hepatitis or fulminant cases 5, 6

Important Cautions

• Never abruptly discontinue treatment due to risk of severe hepatitis flares 2, 7
• Monitor for drug resistance, especially with lamivudine 7
• Be aware of potential nephrotoxicity with adefovir and tenofovir 4
• Lactic acidosis and severe hepatomegaly with steatosis are rare but serious potential complications of nucleoside analogues 4, 7

Treatment Goals

The main goals of therapy are to:

1. Improve survival and quality of life
2. Prevent disease progression to cirrhosis
3. Reduce risk of hepatocellular carcinoma
4. Achieve long-term suppression of HBV replication
5. Ultimately achieve HBsAg loss (optimal endpoint but rare) 1