What medications are used to treat chronic hepatitis B?

Medications to Treat Chronic Hepatitis B

First-Line Treatment Recommendation

For chronic hepatitis B, initiate treatment with entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) as first-line monotherapy—these are the only recommended options due to their superior potency and high genetic barriers to resistance. 1, 2

Preferred First-Line Agents

Nucleos(t)ide Analogues with High Genetic Barrier

• Entecavir: Highly potent oral agent with virologic response rates exceeding 90% after 3 years of treatment 1, 3, 4
• Tenofovir disoproxil fumarate (TDF): Equally potent with similar efficacy to entecavir, achieving 90-96% virologic suppression 1, 5
• Tenofovir alafenamide (TAF): Newer formulation with equivalent efficacy to TDF but improved renal and bone safety profile—particularly important for patients at risk of renal dysfunction or metabolic bone disease 1, 2, 6
• Besifovir: Approved in Korea as first-line therapy with similar efficacy to TDF and favorable renal/bone safety, though clinical data remain more limited 1

Peginterferon Alfa

• Peginterferon alfa-2a: Can be used as first-line therapy with the advantage of finite treatment duration (48-52 weeks) and higher rates of HBsAg loss compared to nucleos(t)ide analogues 1
• Achieves HBeAg seroconversion in 32-41% of HBeAg-positive patients at 6 months post-treatment 1
• Major limitations: Subcutaneous administration, significant side effects, and absolutely contraindicated in decompensated cirrhosis due to risk of liver failure 1

Agents to Avoid as First-Line Therapy

Do not use lamivudine, adefovir, telbivudine, or clevudine as first-line treatment due to inferior efficacy and high resistance rates 1, 2:

• Lamivudine: Resistance rates up to 70% over 5 years 2
• Adefovir: Inferior efficacy and resistance profile compared to tenofovir 1
• Telbivudine: High resistance rates despite potent initial activity 1, 2
• Clevudine: Not recommended due to viral resistance concerns 1

Treatment Selection Algorithm

For Treatment-Naïve Patients

Choose between entecavir, TDF, or TAF based on the following considerations 1, 2:

1. If renal dysfunction or bone disease risk exists: Prefer TAF or entecavir over TDF 1, 2, 6
2. If cost is a primary concern: TDF may be more cost-effective than entecavir in some healthcare systems 7
3. If finite treatment duration is desired and liver function is well-preserved: Consider peginterferon alfa-2a, particularly in HBeAg-positive patients with genotype A 1

For Lamivudine-Experienced Patients

Never use entecavir in patients with any history of lamivudine exposure—archived lamivudine-resistant mutations in HBV cccDNA serve as foundation for entecavir resistance 1, 2

Use tenofovir (TDF or TAF) instead 2

For Patients with Cirrhosis

• Compensated cirrhosis: Use nucleos(t)ide analogues with high genetic barrier (entecavir, TDF, or TAF); peginterferon may be considered with careful monitoring if liver function well-preserved 1
• Decompensated cirrhosis: Immediately initiate nucleos(t)ide analogue monotherapy (entecavir, TDF, or TAF) regardless of HBV DNA level; peginterferon is absolutely contraindicated 1, 2

Treatment Indications by Clinical Scenario

HBeAg-Positive Patients

Initiate treatment when HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal (ULN) 1, 2

HBeAg-Negative Patients

Initiate treatment when HBV DNA >2,000 IU/mL AND ALT elevated 1, 2

Patients with Compensated Cirrhosis

Treat if HBV DNA ≥2,000 IU/mL, regardless of ALT level 2

Patients with Decompensated Cirrhosis

Immediately treat all patients with detectable HBV DNA, regardless of viral load, HBeAg status, or ALT level 2

Treatment Duration

HBeAg-Positive Patients

Continue nucleos(t)ide analogue for minimum 1 year, then 3-6 months after confirmed HBeAg seroconversion 1, 2

HBeAg-Negative Patients

Long-term or indefinite treatment is typically required—relapse rates reach 80-90% if treatment stopped within 1-2 years 1, 2

Patients with Cirrhosis

Indefinite nucleos(t)ide analogue treatment is recommended 1

Peginterferon Alfa

Finite treatment duration of 48-52 weeks 1

Monitoring During Treatment

• HBV DNA and ALT: Every 3-6 months 2
• HBeAg status: Regularly in HBeAg-positive patients 2
• Renal function: Particularly with TDF 2, 5
• Bone density: Consider monitoring in patients on TDF with risk factors 2

Treatment Goals and Expected Outcomes

Primary Goal

Sustained suppression of HBV DNA to undetectable levels to prevent progression to cirrhosis, hepatocellular carcinoma, and liver-related mortality 1, 2

Virologic Response Rates

• Entecavir and TDF: Achieve >90% virologic response after 3 years in treatment-adherent patients 1, 3, 4, 8
• TAF: Achieves 96.7-100% virologic response rates 1

HBsAg Loss (Ideal Endpoint)

• Nucleos(t)ide analogues: 3.4-4.9% HBsAg loss after 10 years of tenofovir treatment 1
• Peginterferon alfa: 2-7% HBsAg loss at 1 year post-treatment, increasing to 12% at 5 years 1

Critical Safety Warnings

Post-Treatment Hepatitis Exacerbation

Severe acute exacerbations of hepatitis can occur after discontinuing anti-HBV therapy—monitor hepatic function closely with clinical and laboratory follow-up for at least several months after stopping treatment 5

Decompensated Cirrhosis

Peginterferon alfa is absolutely contraindicated due to risk of precipitating liver failure 1