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

Treatment Recommendations for Chronic Hepatitis B

The first-line treatment for chronic hepatitis B is entecavir or tenofovir due to their high antiviral potency and low resistance rates, with treatment decisions based on HBV DNA levels, ALT levels, and stage of liver disease. 1

Patient Evaluation and Treatment Criteria

Initial Assessment

• Complete serological evaluation including:
  • HBsAg, anti-HBs, HBeAg, anti-HBe
  • HBV DNA quantification
  • Liver function tests
  • Assessment for coinfections (HCV, HDV, HIV)
  • Alpha-fetoprotein and ultrasound for HCC screening 1
• Fibrosis assessment using non-invasive methods (FibroScan) or liver biopsy in selected cases 1

Treatment Indications

Treatment is recommended for:

1. HBeAg-positive patients:

   • HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal (ULN) 1
   • Moderate to severe inflammation or significant fibrosis on biopsy 2

2. HBeAg-negative patients:

   • HBV DNA >2,000 IU/mL AND ALT >2× ULN 1
   • Evidence of moderate-severe inflammation or fibrosis 2

3. Regardless of HBeAg status:

   • Any patient with cirrhosis and detectable HBV DNA 2
   • Patients receiving immunosuppressive therapy 2
   • Patients with extrahepatic manifestations and active viral replication 2
   • Family history of HCC or cirrhosis 2

First-Line Treatment Options

Preferred Agents

1. Entecavir (0.5 mg daily) 1

   • High potency with <1.2% resistance after 5 years in treatment-naïve patients 2
   • Preferred in patients with renal dysfunction 1

2. Tenofovir disoproxil fumarate (300 mg daily) 1

   • High potency with no reported resistance after 1.5 years 2
   • Tenofovir alafenamide (TAF) may be considered for patients with or at risk for renal/bone disease 1

3. Pegylated interferon alfa-2a (180 μg weekly for 48 weeks) 1

   • Consider for younger patients with high ALT, low HBV DNA, and without cirrhosis
   • Advantage of finite treatment duration but more side effects 2

Treatment Algorithm

1. For most patients: Start with entecavir or tenofovir as monotherapy 1
2. For pregnant women with high viral load: Consider tenofovir in third trimester 1
3. For HIV coinfection: Include tenofovir in HAART regimen 1
4. For decompensated cirrhosis: Start oral antivirals immediately (not interferon) and refer for liver transplant evaluation 2

Treatment Monitoring

• Monitor ALT and HBV DNA every 3-6 months 1
• Check renal function periodically, especially with tenofovir 1
• Annual HCC surveillance with ultrasound and alpha-fetoprotein 1
• For patients on telbivudine, check HBV DNA at week 24 to determine if treatment should continue 2

Treatment Duration and Endpoints

• HBeAg-positive patients: Continue treatment for at least 12 months after HBeAg seroconversion 1
• HBeAg-negative patients: Usually require long-term therapy due to high relapse rates (80-90%) 2, 1
• Ideal endpoint: HBsAg loss with sustained HBV DNA suppression 1
• Cirrhotic patients: Indefinite treatment recommended 2

Management of Treatment Failure

• For lamivudine-resistant HBV, use adefovir in combination with lamivudine 3
• Consider modifying treatment if serum HBV DNA remains above 1000 copies/mL with continued treatment 3
• For treatment failure, add or switch to an antiviral agent that is not cross-resistant 4

Special Considerations

Acute Hepatitis B

• Antiviral therapy only indicated for fulminant hepatitis B or severe/protracted acute hepatitis B 2

Patients Undergoing Immunosuppression

• All HBsAg-positive patients should receive entecavir or tenofovir before starting immunosuppressive therapy 2

Liver Transplantation

• High-potency nucleos(t)ide analogues should be used in patients awaiting or after liver transplantation 2

Cautions and Pitfalls

1. Never abruptly discontinue therapy due to risk of severe hepatitis flares 1
2. Monitor for nephrotoxicity with adefovir and tenofovir, especially in patients with renal dysfunction 3
3. Test for HIV before starting HBV therapy to prevent HIV resistance 3
4. Avoid lamivudine monotherapy when possible due to high resistance rates (up to 70% after 5 years) 2
5. Recognize that HBV cannot be eradicated due to persistence of cccDNA in hepatocytes; treatment aims to suppress viral replication 2

By following these evidence-based recommendations, clinicians can effectively manage chronic hepatitis B to prevent disease progression, cirrhosis, hepatocellular carcinoma, and liver-related mortality.