What is the treatment for hepatitis B (HBV)?

Treatment of Hepatitis B

For chronic hepatitis B, entecavir or tenofovir should be used as first-line monotherapy due to their superior potency and minimal resistance rates, with peginterferon alfa-2a reserved for select patients who prefer finite-duration therapy. 1, 2

First-Line Treatment Selection

Entecavir and tenofovir are the preferred oral agents because they achieve >90% virologic remission after 3 years with extremely low resistance rates (entecavir: <1% at 4 years in treatment-naïve patients; tenofovir: no documented resistance in initial studies). 3, 1, 2

Specific Drug Recommendations:

• Entecavir 0.5 mg daily is appropriate for treatment-naïve patients without prior lamivudine exposure, offering high potency with 1.2% resistance after 5 years. 1, 2

• Tenofovir 300 mg daily (tenofovir disoproxil fumarate) is equally effective and should be the preferred choice for patients with any history of lamivudine use, as prior lamivudine exposure creates archived resistance mutations that predispose to entecavir resistance. 3, 1, 4

• Peginterferon alfa-2a 180 mg weekly subcutaneously for 48 weeks can be considered for younger patients with genotype A or B, high ALT levels, low HBV DNA, and no cirrhosis who desire finite-duration therapy, as it achieves higher rates of HBeAg seroconversion and HBsAg loss compared to oral agents. 3, 1

Treatment Indications Based on Clinical Parameters

HBeAg-Positive Patients:

• Treat if HBV DNA ≥20,000 IU/mL AND ALT >2× upper limit normal (ULN: 30 IU/L for men, 19 IU/L for women). 3, 2
• Treat if HBV DNA ≥2,000 IU/mL with evidence of moderate/severe inflammation or significant fibrosis on biopsy or non-invasive testing. 3, 2

HBeAg-Negative Patients:

• Treat if HBV DNA ≥2,000 IU/mL AND ALT elevated. 3, 2
• Consider biopsy or transient elastography if HBV DNA ≥2,000 IU/mL with normal ALT; treat if disease present. 3

Cirrhotic Patients:

• All patients with compensated or decompensated cirrhosis and HBV DNA ≥2,000 IU/mL should receive treatment regardless of ALT levels. 3, 2
• Use entecavir or tenofovir; peginterferon is contraindicated in decompensated cirrhosis due to risk of hepatic decompensation. 1, 5
• For decompensated cirrhosis, use entecavir 1 mg daily (higher dose than standard). 1

Treatment Duration

HBeAg-Positive Patients:

• Continue treatment for minimum 1 year, then at least 3-6 months after HBeAg seroconversion (loss of HBeAg with appearance of anti-HBe antibody). 3, 1, 2
• If HBeAg seroconversion does not occur, long-term or indefinite treatment is required due to high relapse risk. 2

HBeAg-Negative Patients:

• Long-term or indefinite treatment is typically required, as relapse rates are 80-90% if treatment is stopped within 1-2 years. 3, 1, 2

Cirrhotic Patients:

• Lifelong treatment is recommended for all patients with compensated or decompensated cirrhosis. 1

Monitoring During Treatment

• Monitor HBV DNA and ALT every 3-6 months to assess virologic and biochemical response. 3, 1, 2

• For entecavir: Measure ALT every 6 months. 3

• For tenofovir: Measure baseline serum creatinine and spot urine protein/creatinine ratio, then monitor creatinine and ALT every 6 months due to potential nephrotoxicity. 3, 6

• Monitor HBeAg status in initially HBeAg-positive patients to determine treatment endpoints. 1, 2

• Assess renal function regularly with tenofovir; use with caution and reduced dosing if renal impairment develops, and manage comorbidities like diabetes and hypertension to reduce nephrotoxicity risk. 3, 6

Special Populations

HIV/HBV Co-infection:

• All HIV-infected individuals should be tested for HBsAg. 3
• Use triple antiretroviral therapy including two agents active against HBV: either emtricitabine/tenofovir or lamivudine/tenofovir (preferably as fixed-dose combinations). 3
• Continue treatment for at least 18 months after completion of therapy. 3

Pregnant Women:

• Tenofovir or telbivudine (pregnancy category B) may be used to prevent vertical transmission in HBeAg-positive pregnant women with high viral loads. 3, 1, 2

Children:

• Children with HBV rarely have progressive disease and should only be treated if they have advanced fibrosis or cirrhosis. 3
• Use entecavir for children >2 years of age, or entecavir/tenofovir for children >12 years of age. 3

Cancer Patients Receiving Chemotherapy:

• Patients with chronic HBV (HBsAg-positive) or past exposure (HBsAg-negative, anti-HBc-positive) receiving higher-risk chemotherapy require antiviral prophylaxis with tenofovir or entecavir. 3
• Continue prophylaxis for minimum 12 months after chemotherapy completion (18 months for rituximab-based regimens). 3

Drugs to Avoid

• Lamivudine, emtricitabine, and telbivudine monotherapy should be avoided due to high resistance rates (up to 70% with lamivudine in 5 years) and difficulties monitoring for viral resistance. 3

• Adefovir is no longer first-line due to inferior efficacy and resistance profile compared to tenofovir. 3

• When entecavir and tenofovir are unavailable, combination therapy with adefovir/lamivudine or adefovir/telbivudine should be used rather than monotherapy with these agents. 3

Treatment Goals

• Primary goal: Suppress HBV replication to prevent progression to cirrhosis, liver failure, and hepatocellular carcinoma. 1, 2

• Secondary goals: ALT normalization and histologic improvement. 1

• Optimal endpoint: HBsAg loss with or without anti-HBs seroconversion (functional cure), though this is achieved in only a minority of patients. 3, 2

Critical Warnings

• Never discontinue treatment without consulting a physician, as severe acute exacerbations of hepatitis can occur within 6 months of stopping therapy, potentially leading to hepatic decompensation. 4, 6

• Test for HIV before starting entecavir or tenofovir in HBV monoinfection, as these drugs have anti-HIV activity and could lead to HIV resistance if HIV is present but untreated. 4

• Monitor for lactic acidosis, particularly in patients who are female, very overweight, or on long-term nucleoside analogue therapy; symptoms include unusual muscle pain, trouble breathing, stomach pain with nausea/vomiting, dizziness, and fast/irregular heartbeat. 4, 6

• Hepatocellular carcinoma surveillance should continue even during successful treatment, following existing practice guidelines, as treatment reduces but does not eliminate HCC risk. 3