What is the treatment for hepatitis B?

Treatment for Hepatitis B

First-line treatment for chronic hepatitis B should be entecavir or tenofovir due to their high potency and high genetic barrier to resistance. 1, 2

Patient Assessment and Treatment Indications

• Treatment decisions should be based on HBeAg status, HBV DNA levels, ALT levels, and liver disease severity 1, 2
• For HBeAg-positive patients with ALT >2 times normal or moderate/severe hepatitis on biopsy, treatment is recommended after observing for 3-6 months for possible spontaneous HBeAg seroconversion 2
• For HBeAg-negative patients, treatment is indicated with HBV DNA ≥2,000 IU/mL and ALT ≥2 times normal or moderate/severe hepatitis on biopsy 1
• Patients with persistently normal or minimally elevated ALT (<2 times normal) should not be initiated on treatment unless liver biopsy shows moderate/severe inflammation 2
• All patients with cirrhosis and detectable HBV DNA should be treated regardless of ALT levels 1, 3

First-Line Treatment Options

• Entecavir and tenofovir are preferred first-line agents due to their high potency and high genetic barrier to resistance 4, 1
• Tenofovir has shown histological improvement in 88% of patients by week 240 and regression of cirrhosis in 72% of cirrhotic patients 5
• Monotherapy with lamivudine, emtricitabine, and telbivudine should be avoided due to high rates of resistance 4
• When entecavir and tenofovir are not available, combination therapy with adefovir/lamivudine or adefovir/telbivudine is recommended 4
• Interferon-α can be used for specific subgroups as recommended in practice guidelines, provided appropriate monitoring is available 4, 2

Special Populations

HBV/HIV Co-infection

• Co-infected patients with an indication for treatment of either HBV and/or HIV should receive a triple combination of antiretroviral agents, including two that are active against HBV (either emtricitabine/tenofovir or lamivudine/tenofovir, preferably as fixed-dose formulations) 4
• In patients already being treated with lamivudine without tenofovir who are found to be HBsAg-positive, treatment should be changed to include two drugs that target HBV, one of which should be tenofovir 4

Cirrhosis

• For patients with compensated cirrhosis, entecavir or tenofovir is recommended 1, 2
• For patients with decompensated cirrhosis, lamivudine or tenofovir is recommended with close monitoring of renal function 2, 5
• Interferon-α is contraindicated in decompensated cirrhosis due to risk of serious complications 2

Children

• Children with elevated ALT >2 times normal for >6 months should be considered for treatment 2
• Interferon-α dose for children: 6 MU/m² thrice weekly (maximum 10 MU) 2
• Lamivudine dose for children: 3 mg/kg/day (maximum 100 mg/day) 2

Treatment Duration

• For HBeAg-positive patients, minimum 1 year of treatment, continuing for 3-6 months after HBeAg seroconversion 1, 2
• For HBeAg-negative patients, longer treatment duration is typically required, with optimal duration not established 1, 2
• For patients with cirrhosis, indefinite treatment is generally recommended 1

Monitoring During Treatment

• Regular assessment of HBV DNA levels to evaluate virological response 4, 1
• Monitor ALT every 6 months for patients on entecavir 4
• For patients on tenofovir: measure baseline serum creatinine, spot urine protein creatinine ratio if possible, and monitor ALT and serum creatinine every 6 months 4
• Baseline alpha-fetoprotein and ultrasound in patients at risk of HCC 4

Management of Treatment Failure

• Lamivudine resistance: Switch to adefovir, especially with worsening liver disease, decompensated cirrhosis, or need for immunosuppressive therapy 2
• Prior interferon-α failure: May be retreated with lamivudine or adefovir if they meet treatment criteria 2
• Viral resistance to lamivudine occurs in up to 70% of persons during the first 5 years of treatment 4
• Lower rates of resistance have been observed with adefovir (30% in 5 years), entecavir (<1% at 4 years), and telbivudine (2.3%-5% in 1 year) 4, 6

Common Pitfalls and Caveats

• Strict adherence to ALT thresholds in guidelines may result in missed opportunities to treat patients with significant underlying liver disease 7
• Severe acute exacerbations of hepatitis have been reported in patients infected with HBV who have discontinued treatment 5
• Sequential monotherapy may result in multi-drug resistant virus 6, 7
• The rapidity and robustness of HBV DNA suppression while on nucleoside analogs should be monitored early during treatment as it affects treatment outcome and resistance rates 7
• In the treatment of chronic hepatitis B, the relationship between response and long-term prevention of outcomes such as hepatocellular carcinoma is not fully established 5