Hepatitis B — chronic infection

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.

References

1.EASL Clinical Practice Guidelines on the Management of Hepatitis B Virus Infection (2025) (2025)