Red Flags
- Acute liver failure on chronic hepatitis B (jaundice, INR ≥1.5, encephalopathy) — emergency transplant centre referral; immediate antiviral[1]
- Hepatocellular carcinoma identified on surveillance — multidisciplinary hepatobiliary meeting; multiphasic CT or MRI[1]
- Reactivation of HBV during immunosuppression (rising HBV-DNA or ALT) — start nucleos(t)ide analogue immediately, do not wait for hepatitis[1]
- HBeAg-positive or HBV-DNA >200,000 IU/mL in pregnancy — start tenofovir at week 24–28 to prevent vertical transmission[1]
First-line treatment
Interventions
- Phase-based treatment indication[1]Treat HBeAg-positive or HBeAg-negative chronic hepatitis (HBV-DNA >2000 IU/mL with elevated ALT or histologic activity); cirrhosis with detectable HBV-DNA at any level; immunosuppression-related reactivation; pregnancy with high viraemia
- HCC surveillance with ultrasound + AFP every 6 months[1]Cirrhosis at any HBV-DNA level; non-cirrhotic Asian men >40 or women >50; family history of HCC; co-existent HDV; persistent ALT elevation despite treatment
- Antiviral prophylaxis for immunosuppression[1]All HBsAg-positive patients receiving anti-CD20 (rituximab), corticosteroids ≥10 mg prednisolone equivalent for ≥4 weeks, BMT, or solid organ transplant — start TAF/TDF/entecavir before therapy and continue ≥12 months after immunosuppression ends
- Vertical transmission prevention[1]HBeAg-positive or HBV-DNA >200,000 IU/mL: start tenofovir at week 24–28 of pregnancy; HBIG + birth-dose vaccine to neonate within 12 h; complete vaccination series; check infant HBsAg/anti-HBs at 9–12 months
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Tenofovir alafenamide (TAF)[1] | Nucleotide analogue reverse transcriptase inhibitor | 25 mg PO once daily | Children ≥12 years and ≥35 kg: 25 mg PO once daily | First-line for chronic HBV; preferred over TDF in CKD G3+, osteoporosis, or pre-/post-transplant; high genetic barrier to resistance |
| Tenofovir disoproxil fumarate (TDF)[1] | Nucleotide analogue reverse transcriptase inhibitor | 300 mg PO once daily | ≥12 years and ≥35 kg: 300 mg daily; weight-based for younger | First-line for chronic HBV including pregnancy (most data); monitor for renal tubular injury and bone mineral density; preferred in pregnancy |
| Entecavir[1] | Nucleoside analogue reverse transcriptase inhibitor | 0.5 mg PO once daily on empty stomach (1 mg if lamivudine-resistant or decompensated cirrhosis) | ≥2 years weight-based per package insert | First-line alternative; high genetic barrier; renal dose adjustment; not preferred in pregnancy due to limited data |
| Pegylated interferon alpha-2a (selected)[1] | Pegylated interferon | 180 µg SC once weekly × 48 weeks | — | Selected HBeAg-positive without cirrhosis; younger patients; genotype A; ALT 2–5× ULN; finite duration with chance of HBsAg loss; many side effects, contraindicated in decompensated cirrhosis and pregnancy |
Tenofovir alafenamide (TAF)[1]
Nucleotide analogue reverse transcriptase inhibitor
- Adult
- 25 mg PO once daily
- Paediatric
- Children ≥12 years and ≥35 kg: 25 mg PO once daily
First-line for chronic HBV; preferred over TDF in CKD G3+, osteoporosis, or pre-/post-transplant; high genetic barrier to resistance
Tenofovir disoproxil fumarate (TDF)[1]
Nucleotide analogue reverse transcriptase inhibitor
- Adult
- 300 mg PO once daily
- Paediatric
- ≥12 years and ≥35 kg: 300 mg daily; weight-based for younger
First-line for chronic HBV including pregnancy (most data); monitor for renal tubular injury and bone mineral density; preferred in pregnancy
Entecavir[1]
Nucleoside analogue reverse transcriptase inhibitor
- Adult
- 0.5 mg PO once daily on empty stomach (1 mg if lamivudine-resistant or decompensated cirrhosis)
- Paediatric
- ≥2 years weight-based per package insert
First-line alternative; high genetic barrier; renal dose adjustment; not preferred in pregnancy due to limited data
Pegylated interferon alpha-2a (selected)[1]
Pegylated interferon
- Adult
- 180 µg SC once weekly × 48 weeks
- Paediatric
- —
Selected HBeAg-positive without cirrhosis; younger patients; genotype A; ALT 2–5× ULN; finite duration with chance of HBsAg loss; many side effects, contraindicated in decompensated cirrhosis and pregnancy
Safety-net
- Do not stop antiviral therapy without specialist supervision — discontinuation can trigger flares including life-threatening hepatitis[1]
- Family members and sexual partners should be tested and vaccinated if not immune; avoid sharing razors, toothbrushes, needles[1]
- Yellowing of eyes/skin, abdominal swelling, confusion, or vomiting blood — same-day medical review (cirrhosis decompensation)[1]
Referral criteria
- All chronic HBsAg-positive patientsHepatology or gastroenterology for staging and treatment decision[1]
- Cirrhosis, decompensation, HCC, or transplant evaluationHepatology and transplant centre[1]
- HDV co-infection (anti-HDV positive with HDV-RNA detectable)Specialist hepatology — bulevirtide or interferon-based therapy[1]
- Pregnancy with chronic HBV and high viraemiaJoint hepatology and obstetric clinic by week 24[1]
Clinical summary
Diagnosis, phase classification, treatment indication, and antiviral choice for adults with chronic hepatitis B; HCC surveillance and pregnancy management.