Treatment of Hepatitis B (HBV)
For chronic hepatitis B, first-line treatment should be either entecavir or tenofovir (disoproxil fumarate or alafenamide), as these agents have superior potency, high genetic barriers to resistance, and the best long-term outcomes for preventing cirrhosis and hepatocellular carcinoma. 1, 2, 3
First-Line Treatment Options
The preferred agents are:
Entecavir 0.5 mg daily (orally): Achieves >90% virologic suppression after 3 years with resistance rates of only 1.2% at 5 years in treatment-naïve patients 1, 2, 4
Tenofovir disoproxil fumarate (TDF) 300 mg daily (orally): Achieves >90% virologic suppression after 3 years with minimal documented resistance 1, 2, 3
Tenofovir alafenamide (TAF): 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 3
Peginterferon alfa-2a 180 mg weekly (subcutaneous for 48 weeks): Has higher rates of HBeAg seroconversion and HBsAg loss compared to oral agents, especially in patients with genotype A or B, high ALT, low HBV DNA, and younger age 1, 2, 5
Treatment Indications Based on Clinical Scenario
For HBeAg-positive patients:
- Initiate treatment when HBV DNA >20,000 IU/mL AND ALT >2× upper limit of normal (ULN) 3
- If HBV DNA >2,000 IU/mL with elevated ALT, consider biopsy or transient elastography; treat if disease present 1
For HBeAg-negative patients:
- Initiate treatment when HBV DNA >2,000 IU/mL AND ALT >2× ULN 1, 3
- Long-term treatment is typically required with oral agents 1, 2
For compensated cirrhosis:
- Treat if HBV DNA ≥2,000 IU/mL, regardless of ALT level 3, 4
- Entecavir or tenofovir are strongly preferred; peginterferon may be considered in select patients 2
For decompensated cirrhosis:
- Immediately treat all patients with detectable HBV DNA, regardless of HBV DNA level, HBeAg status, or ALT level 3
- Use entecavir 1 mg daily or tenofovir; peginterferon is contraindicated 2
Agents to Avoid as First-Line Therapy
Do not use lamivudine, adefovir, or telbivudine as first-line therapy due to high resistance rates (lamivudine resistance reaches 70% over 5 years) and inferior efficacy compared to entecavir and tenofovir 1, 3
Treatment Duration
For HBeAg-positive patients:
- Continue nucleos(t)ide analogue for at least 1 year, then 3-6 months after HBeAg seroconversion 2, 3, 4
For HBeAg-negative patients:
- Long-term or indefinite treatment is typically required, as relapse rates reach 80-90% if stopped within 1-2 years 3, 6
For patients with cirrhosis:
- Lifelong treatment is generally required 2
Special Populations
Lamivudine-experienced patients:
- Avoid entecavir due to risk of cross-resistance from archived mutations in HBV cccDNA 1, 2, 3
- Use tenofovir (TDF or TAF) instead 3
Pregnant women:
- Telbivudine or tenofovir may be preferred during pregnancy (pregnancy category B) to prevent vertical transmission 1, 4
Patients with renal dysfunction:
Monitoring During Treatment
- HBV DNA and ALT every 3-6 months to assess virologic and biochemical response 1, 2, 3
- HBeAg status regularly in HBeAg-positive patients 2, 3
- Renal function (serum creatinine, spot urine protein/creatinine ratio) at baseline and every 6 months, particularly with tenofovir 1, 3
- Bone density monitoring in patients on TDF with risk factors 3
Treatment Goals
The primary goal is sustained suppression of HBV DNA to undetectable levels to prevent progression to cirrhosis, liver failure, and hepatocellular carcinoma 2, 3, 4
The ideal endpoint is HBsAg loss with or without anti-HBs seroconversion, though this is rarely achieved (approximately 2% at 10 years with oral agents) 3, 4, 8
Critical Warnings
Never stop treatment abruptly without medical supervision, as hepatitis B exacerbations with severe ALT elevations can occur after discontinuation, with fatalities reported in some cases 7, 9
HIV testing is mandatory before starting treatment, as subtherapeutic HBV treatment in unrecognized HIV co-infection can lead to rapid HIV resistance 7, 9