Treatment of Chronic Hepatitis B
Entecavir or tenofovir are the recommended first-line treatments for chronic hepatitis B due to their high potency and high genetic barrier to resistance. 1
Patient Assessment and Treatment Indications
- Treatment is indicated for chronic hepatitis B patients with HBV DNA levels ≥2,000 IU/mL and ALT levels >2 times upper limit of normal 1
- Patients with evidence of moderate to severe liver inflammation or significant fibrosis on biopsy should be considered for treatment regardless of ALT levels 2, 1
- For HBeAg-positive patients with elevated ALT, observation for 3-6 months is recommended to assess for spontaneous seroconversion before initiating treatment 2
- Patients with cirrhosis and detectable HBV DNA should receive treatment regardless of ALT levels 1
First-Line Treatment Options
- Entecavir is recommended as a first-line treatment option due to its high potency and low resistance rate (1.2% after 5 years in treatment-naïve patients) 1, 3
- Tenofovir is equally recommended as a first-line treatment due to its high potency and no documented resistance in treatment-naïve patients after long-term studies 1, 2
- Both medications have demonstrated superior efficacy compared to older agents like lamivudine and adefovir 2
- In a pooled analysis of tenofovir studies, 51% of patients showed regression of fibrosis after 5 years of treatment, and 74% of patients with baseline cirrhosis no longer had cirrhosis 2
Treatment Duration
- For HBeAg-positive patients, treatment should continue for at least 1 year, with continuation for 3-6 months after HBeAg seroconversion 2, 1
- For HBeAg-negative patients, long-term or indefinite treatment is often required due to high relapse rates after discontinuation 2, 1
- Patients with cirrhosis generally require lifelong treatment 2, 1
- The ideal endpoint for all patients is HBsAg loss with or without anti-HBs seroconversion, though this is rarely achieved 1
Special Populations
Patients with Cirrhosis
- Patients with decompensated cirrhosis should receive oral antiviral therapy (not interferon) and be referred for liver transplant evaluation 2
- Nucleos(t)ide analogues with high genetic barriers to resistance (entecavir, tenofovir) are preferred 1
Patients with Lamivudine Resistance
- Tenofovir is the preferred treatment for patients with lamivudine resistance 2
- Entecavir should not be used in patients with prior lamivudine experience due to increased risk of resistance 2
Pregnant Women
- Telbivudine or tenofovir may be preferred during pregnancy due to their pregnancy category B classification 1, 4
Monitoring During Treatment
- Regular assessment of HBV DNA levels every 3-6 months to evaluate virological response 1
- Monitoring of liver function tests to assess biochemical response 1
- For patients on tenofovir, renal function should be monitored due to potential nephrotoxicity 4
- For patients on entecavir, regular monitoring is still required though the side effect profile is favorable 3, 5
Managing Treatment Failure and Resistance
- Primary non-response should be assessed after 12 weeks of therapy 1
- For patients with viral breakthrough on lamivudine or telbivudine, switching to tenofovir is recommended 2
- For adefovir resistance, tenofovir is generally effective as monotherapy 2
- Combination therapy is rarely needed for treatment-naïve patients when using high-barrier agents like entecavir or tenofovir 2
Potential Pitfalls and Caveats
- Severe acute exacerbations of hepatitis can occur upon discontinuation of therapy, requiring close monitoring of hepatic function for several months after stopping treatment 4, 6
- Non-adherence to medication is a common cause of virological breakthrough rather than true resistance 1
- Patients with unrecognized HIV co-infection may develop HIV resistance if treated with anti-HBV medications that have anti-HIV activity 6
- Renal impairment may require dose adjustment for both adefovir and tenofovir 4, 6