What are the recommended medications for treating hepatitis B?

Hepatitis B Medication

First-Line Treatment Recommendations

For chronic hepatitis B, initiate treatment with entecavir or tenofovir (either tenofovir disoproxil fumarate [TDF] or tenofovir alafenamide [TAF]) as first-line monotherapy due to their superior potency and high genetic barriers to resistance. 1, 2

Preferred Agents

• Entecavir and tenofovir are the only recommended first-line options, with resistance rates of <1% at 4 years for entecavir and essentially no documented resistance for tenofovir in treatment-naïve patients 2, 3, 4
• Tenofovir alafenamide (TAF) is equally effective as tenofovir disoproxil fumarate but offers improved renal and bone safety, making it preferable for patients at risk of renal dysfunction or metabolic bone disease 1
• Peginterferon alfa-2a can be used as first-line therapy for specific subgroups who prefer finite treatment duration (48 weeks for HBeAg-positive, 1 year for HBeAg-negative), though it requires subcutaneous injection and has more side effects 2, 4

Agents to Avoid

• Do not use lamivudine, adefovir, or telbivudine as first-line therapy due to high resistance rates (lamivudine: up to 70% over 5 years; adefovir: 30% in 5 years; telbivudine: intermediate resistance) 2, 1, 2
• These older agents are only acceptable when entecavir and tenofovir are unavailable, and then preferably in combination (adefovir/lamivudine or adefovir/telbivudine) 2

Treatment Indications by Clinical Scenario

HBeAg-Positive Patients

• Initiate treatment when HBV DNA ≥20,000 IU/mL (or ≥10^5 copies/mL) AND ALT ≥2× upper limit of normal 1, 2, 5
• Observe for 3-6 months for possible spontaneous HBeAg seroconversion before starting treatment, unless cirrhosis is present 2, 5
• Treatment duration: minimum 1 year, then continue for 3-6 months after confirmed HBeAg seroconversion 2, 1, 3

HBeAg-Negative Patients

• Initiate treatment when HBV DNA ≥2,000 IU/mL AND ALT ≥2× upper limit of normal 1, 2, 3
• Long-term or indefinite treatment is typically required, as relapse rates reach 80-90% if stopped within 1-2 years 2, 1, 3
• Consider liver biopsy or transient elastography if ALT is normal but HBV DNA is elevated to assess for significant liver disease 2

Compensated Cirrhosis

• Treat if HBV DNA ≥2,000 IU/mL, regardless of ALT level 1, 3
• Use entecavir or tenofovir; avoid interferon due to risk of hepatic decompensation from interferon-related hepatitis flares 2, 5

Decompensated Cirrhosis

• Immediately treat all patients with detectable HBV DNA, regardless of level, HBeAg status, or ALT 1
• Use entecavir or tenofovir; interferon is absolutely contraindicated 2, 5
• Coordinate treatment with transplant center and refer for liver transplantation 2
• Monitor renal function closely if using tenofovir (BUN and creatinine every 1-3 months) 2, 5

Special Populations

Lamivudine-Experienced Patients

• Avoid entecavir in patients with any history of lamivudine use due to archived resistance mutations in HBV cccDNA that increase entecavir resistance risk 2, 1
• Use tenofovir (TDF or TAF) as the preferred option 1

Patients with Renal Dysfunction

• Switch from tenofovir DF to tenofovir AF or entecavir based on prior treatment history 1
• Dose adjustment required for tenofovir DF and adefovir when creatinine clearance <50 mL/min 6, 7

Pregnant Women

• Telbivudine (pregnancy category B) has a role in preventing vertical transmission in HBeAg-positive pregnant women, despite not being first-line for other indications 2, 3

Pediatric Patients

• For chronic hepatitis B: tenofovir approved for ages ≥12 years (≥35 kg); entecavir data available for treatment-naïve patients 6
• Children rarely have progressive disease and should only be treated if advanced fibrosis or cirrhosis is present 2

HIV/HBV Coinfection

• Use triple antiretroviral therapy including two agents active against HBV: emtricitabine/tenofovir or lamivudine/tenofovir (preferably as fixed-dose combinations) 2
• If already on lamivudine without tenofovir, add tenofovir to the regimen 2

Monitoring During Treatment

• HBV DNA and ALT every 3-6 months to assess virologic and biochemical response 1, 3
• HBeAg status regularly in HBeAg-positive patients to determine treatment endpoint 1, 3
• Renal function monitoring (serum creatinine, spot urine protein/creatinine ratio) at baseline and every 6 months, particularly with tenofovir DF 2, 1
• Bone density monitoring in patients on tenofovir DF with risk factors for osteoporosis 1

Managing Treatment Failure

Partial Virologic Response

• Switch to tenofovir (DF or TAF) if on lamivudine or telbivudine 1
• Add tenofovir if on entecavir 1

Lamivudine Resistance

• Switch to adefovir or tenofovir, especially if worsening liver disease, decompensated cirrhosis, or need for immunosuppressive therapy 2, 5

Drug Resistance

• Switch to tenofovir (DF or TAF) or combine entecavir with tenofovir 1

Treatment Goals

• Primary goal: Sustained suppression of HBV DNA to undetectable levels by sensitive PCR assay to prevent progression to cirrhosis, liver failure, and hepatocellular carcinoma 1, 3
• Secondary goals: ALT normalization and histologic improvement 1
• Ideal endpoint: HBsAg loss with or without anti-HBs seroconversion 1, 3

Critical Warnings

Post-Treatment Hepatitis Exacerbation

• Severe acute exacerbations of hepatitis can occur after discontinuing anti-HBV therapy 6
• Monitor hepatic function closely with clinical and laboratory follow-up for at least several months after stopping treatment 6
• Resumption of anti-HBV therapy may be warranted if exacerbation occurs 6

Immunosuppressive Therapy

• Hepatitis B carriers receiving immunosuppressive or cancer chemotherapy have 20-50% risk of HBV reactivation 2
• Administer antiviral prophylaxis (entecavir or tenofovir preferred) to reduce frequency and severity of hepatitis flares and improve survival 2