Morphology: Enveloped, partially double-stranded DNA virus. Family Hepadnaviridae. Replicates via RNA intermediate (reverse transcription). Hepatocyte tropism; persists as cccDNA (covalently closed circular DNA) in nucleus — basis of chronic infection + reactivation risk.
Typical drugs
- #1Tenofovir Alafenamide— **25 mg PO daily** — first-line. Better renal + bone safety than TDF.
- #2Entecavir— **0.5 mg PO daily** (1 mg if lamivudine-experienced). Very high resistance barrier. Take on empty stomach.
Empiric therapy when resistant
TAF + entecavir have very high resistance barriers. Treatment failure → check adherence first, then sequence for resistance mutations.
Resistance mechanisms
altered-target
rt-M204V/I (YMDD motif) → lamivudine resistance
Example: Why lamivudine is no longer first-line; entecavir + TAF have higher genetic barriers.
Resistance notes
TDF, TAF, entecavir all have >95% suppression rates with low resistance over years.
Pearls
5 serologic patterns: (1) immune from vaccine = anti-HBs+ only; (2) immune from past infection = anti-HBs+ + anti-HBc+; (3) acute = HBsAg+ + IgM anti-HBc+; (4) chronic = HBsAg+ × ≥6 mo; (5) window phase = anti-HBc+ only. Treatment indications (AASLD): HBeAg+ with ALT >2× ULN or chronic disease with significant inflammation/fibrosis; HBeAg− with ALT >2× ULN + HBV DNA >2000; cirrhosis with any HBV DNA; reactivation prevention in immunosuppression. HBV reactivation is critical concern with chemo / biologics / rituximab / steroids — check HBsAg + anti-HBc before starting; treat with TAF/ETV prophylaxis. HBV co-infection with HCV / HIV / HDV changes management. Vaccine + HBIG for PEP (perinatal, needle stick, sexual exposure). HCC screening with US ± AFP q6mo in cirrhotic + high-risk non-cirrhotic.
References
- AASLD HBV Practice Guidance (2018)
- WHO Hepatitis B Guidelines (2024)