A 35-year-old man from Mumbai is found to have HBeAg-positive chronic hepatitis B with HBV DNA >10^5 copies/mL and elevated transaminases (ALT 180 U/L). He has no evidence of cirrhosis. What is the drug of choice for initiating antiviral therapy?

Explanation

## First-Line Antiviral Therapy in Chronic HBV **Key Point:** Tenofovir disoproxil fumarate (TDF) is the preferred first-line nucleotide reverse transcriptase inhibitor (NtRTI) for treatment-naïve patients with chronic hepatitis B, especially those with high viral loads and active inflammation. ### Why Tenofovir is Preferred **High-Yield:** Tenofovir offers: 1. **Potent viral suppression** — reduces HBV DNA by >6 log~10~ copies/mL 2. **Low resistance barrier** — resistance rates <1% at 5 years in treatment-naïve patients 3. **Broad activity** — effective against wild-type and lamivudine-resistant strains 4. **Renal safety profile** — acceptable in most patients (monitor baseline renal function) ### Comparison of First-Line Agents | Agent | Potency | Resistance (5 yr) | Renal Concern | Use | |-------|---------|-------------------|---------------|-----| | **Tenofovir (TDF)** | Very high | <1% | Monitor | **First-line** | | **Entecavir** | Very high | <1% (naïve) | No | Alternative first-line | | **Lamivudine** | Moderate | 70% | No | **Avoid — high resistance** | | **Adefovir** | Moderate | 29% | Yes | Salvage only | **Clinical Pearl:** In this patient with HBeAg positivity and high viral load (>10^5 copies/mL), potent first-line therapy is mandatory to prevent progression to cirrhosis and HCC. Lamivudine monotherapy is now considered suboptimal due to rapid resistance emergence. **Warning:** Do not use lamivudine or adefovir as monotherapy in treatment-naïve patients — resistance develops rapidly and limits future options. ### Treatment Endpoint Therapy continues until: - HBeAg seroconversion (HBeAg loss + anti-HBe appearance) + undetectable HBV DNA for ≥6 months, OR - Development of cirrhosis (indefinite therapy) [cite:Harrison 21e Ch 295]