What are the recommended medications for treating Hepatitis B?

Hepatitis B Medication

First-Line Treatment Recommendations

Entecavir or tenofovir are the preferred first-line medications for chronic hepatitis B, with both achieving >90% viral suppression and having high barriers to resistance. 1, 2

Preferred Agents

• Entecavir 0.5 mg daily achieves virologic suppression (HBV DNA <50 IU/mL) in 83% of patients after 96 weeks, with no genotypic resistance detected after 8 years in treatment-naive patients 2
• Tenofovir disoproxil fumarate (TDF) 300 mg daily demonstrates 93% virologic suppression at 48 weeks and maintains efficacy even with baseline viral loads ≥9 log10 copies/mL, with no resistance after 8 years 2, 3
• Tenofovir alafenamide (TAF) is equally effective as TDF but with improved renal and bone safety profile, particularly important for patients at risk of renal dysfunction or metabolic bone disease 2
• Peginterferon alfa-2a 180 mg/week subcutaneously for 48 weeks (HBeAg-positive) or 1 year (HBeAg-negative) offers finite treatment duration with higher rates of HBeAg seroconversion (32%) and HBsAg loss compared to oral agents 1

Treatment Indications by Clinical Scenario

HBeAg-Positive Patients

• Initiate treatment when HBV DNA >20,000 IU/mL AND ALT >2× ULN 1, 2
• Observe for 3-6 months for spontaneous HBeAg seroconversion before starting therapy if compensated liver disease 1
• Consider treatment even with ALT <2× ULN if family history of HCC or cirrhosis exists 2

HBeAg-Negative Patients

• Initiate treatment when HBV DNA ≥2,000 IU/mL AND ALT >2× ULN 1, 2
• Long-term or indefinite treatment typically required, as relapse rates reach 80-90% if stopped within 1-2 years 2

Compensated Cirrhosis

• Treat if HBV DNA ≥2,000 IU/mL, regardless of ALT level 1, 2
• Strongly prefer entecavir and tenofovir over lamivudine due to high resistance rates with lamivudine that could precipitate decompensation 2

Decompensated Cirrhosis

• Immediately treat all patients with any detectable HBV DNA, regardless of viral load level, HBeAg status, or ALT 1, 2, 4
• Consider combination therapy with tenofovir plus lamivudine or entecavir monotherapy to minimize resistance risk 2
• Peginterferon is absolutely contraindicated due to risk of further decompensation 1, 2
• Coordinate treatment with transplant center and refer for liver transplant evaluation 1

Agents to Avoid as First-Line Therapy

• Do not use lamivudine as first-line due to resistance rates up to 70% over 5 years, though it remains acceptable for short-term prophylaxis during chemotherapy or pregnancy 1, 2
• Do not use adefovir as first-line because efficacy and resistance profiles are inferior to tenofovir 1, 2, 5
• Do not use telbivudine as first-line due to high resistance rates despite potent antiviral activity, plus risk of serious muscle-related complications 2

Treatment Duration

HBeAg-Positive Patients

• Minimum 1 year with oral agents, continuing 3-6 months after HBeAg seroconversion is confirmed on two occasions at least 2 months apart 1, 2, 4
• Peginterferon: 48 weeks (16 weeks in older guidelines) 1

HBeAg-Negative Patients

• Long-term or indefinite treatment required with oral agents 1, 2
• Peginterferon: 1 year 1

Cirrhotic Patients

• Lifelong therapy recommended for all patients with decompensated cirrhosis and majority with compensated cirrhosis (F3-F4 fibrosis) at treatment start 1, 2
• May discontinue only if HBsAg loss occurs for 6-12 months or longer, but lifelong HCC screening still required 1, 2

Special Populations and Situations

Lamivudine-Experienced Patients

• Avoid entecavir due to increased risk of resistance from archived mutations in HBV covalently closed circular DNA, even if prior lamivudine exposure was brief 1, 2
• Prefer tenofovir (TDF or TAF) instead 2

Adefovir-Resistant Patients

• Switch to tenofovir monotherapy or tenofovir/entecavir combination 2
• Patients with both rtA181T/V and rtN236T mutations may have inferior response to tenofovir monotherapy and require close monitoring 2

Pediatric Patients

• Age ≥12 years: Entecavir 0.5 mg daily or tenofovir 8 mg/kg daily (maximum 300 mg) 1, 4, 3
• Age 2-11 years: Weight-based tenofovir dosing available for those weighing ≥17 kg 3
• Children with HBV rarely have progressive disease and should only be treated if advanced fibrosis or cirrhosis present 1

Renal Impairment

• Creatinine clearance 30-49 mL/min: Tenofovir 300 mg every 48 hours 3
• Creatinine clearance 10-29 mL/min: Tenofovir 300 mg every 72 hours 3
• Hemodialysis patients: Tenofovir 300 mg every 7 days following dialysis 3
• Adefovir requires dose adjustment for creatinine clearance <50 mL/min, with close monitoring of renal function (BUN and creatinine every 1-3 months) 1, 4, 5

HIV/HBV Co-infection

• All HBV/HIV co-infected patients should receive triple combination antiretroviral therapy including two agents active against HBV (emtricitabine/tenofovir or lamivudine/tenofovir, preferably as fixed-dose formulations) 1, 2
• Lamivudine dose for HIV co-infection: 150 mg twice daily along with other antiretroviral medications 1, 4

Pregnancy

• Telbivudine (pregnancy category B) has a role in preventing vertical transmission in HBeAg-positive pregnant women 1
• Women on antiviral therapy who become pregnant may continue treatment or stop and restart after pregnancy, weighing fetal risk against mother's liver disease stage 1

Managing Inadequate Response

Virologic Breakthrough

• First verify medication adherence—this is the most common cause of breakthrough rather than true resistance 1, 2
• For confirmed lamivudine resistance: Switch to tenofovir or add tenofovir to current regimen 1, 2
• For partial virologic response on entecavir: Add tenofovir 2

Prior Interferon Failure

• May be retreated with entecavir or tenofovir if they meet treatment criteria 1, 4

Monitoring Requirements

• Before treatment: Test for HBV and HIV infection; assess serum creatinine, estimated creatinine clearance, urine glucose, urine protein; in chronic kidney disease patients also assess serum phosphorus 3
• During treatment: Monitor HBV DNA and ALT every 3-6 months 2
• With tenofovir: Monitor renal function (serum creatinine, spot urine protein/creatinine ratio) every 6 months; consider bone density monitoring in patients with risk factors 1, 2
• After discontinuation: Monitor hepatic function closely with clinical and laboratory follow-up for at least several months, as severe acute exacerbations can occur 3, 5

Critical Pitfalls to Avoid

• Never use entecavir in patients with any prior lamivudine exposure, even if brief, due to risk of archived resistance mutations 2
• Never discontinue therapy prematurely in HBeAg-negative patients or those with cirrhosis, as this can lead to severe hepatitis flares 2
• Never use combination therapy as initial treatment in treatment-naive patients unless decompensated cirrhosis is present, as monotherapy with entecavir or tenofovir is equally effective and reduces cost and potential toxicity 2
• Never assume virologic breakthrough represents resistance without first confirming medication adherence 2
• Never use tenofovir alone in HIV-infected patients—this can lead to HIV resistance 3
• Never use interferon in decompensated cirrhosis due to risk of serious complications and further decompensation 1, 2, 4