Treatment information
First-line oral nucleos(t)ide analogues (NAs): tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir (ETV). Per CASL/AMMI 2025.
Indications for antiviral therapy
Treat when any of the following are present:
- Cirrhosis (compensated or decompensated) with any detectable HBV DNA — treat regardless of ALT.
- HBV DNA > 2,000 IU/mL and ALT above the upper limit of normal (sex-specific ULN: ♂ ≤ 30 U/L, ♀ ≤ 19 U/L), particularly with significant inflammation or fibrosis.
- Significant fibrosis (≥ F2 / LSM ≥ 7 kPa) with detectable HBV DNA.
- Age > 40 in the immune-active or "grey zone"/indeterminate phase, to reduce long-term HCC risk (expanded 2025 indication).
- Prevention of mother-to-child transmission: HBV DNA > 200,000 IU/mL in the late second / early third trimester.
- Prophylaxis for HBsAg-positive (or at-risk isolated anti-HBc–positive) patients undergoing immunosuppression or chemotherapy.
- Extrahepatic manifestations (e.g., HBV-associated vasculitis, glomerulonephritis); acute liver failure or severe acute hepatitis B.
Agent selection
| Agent | Preferred when | Notes |
|---|---|---|
| TDF | Most patients; pregnancy; known/suspected NA resistance | Use TAF instead if renal impairment or osteoporosis risk |
| TAF | eGFR < 60, CKD, osteoporosis / low bone density, older patients | Favorable renal and bone profile; not for eGFR < 15 off dialysis |
| Entecavir | Treatment-naïve without prior lamivudine resistance | Avoid in pregnancy; reduced efficacy if lamivudine-resistant |
Contraindications & cautions
- Entecavir: avoid in pregnancy (insufficient human safety data); reduced efficacy with prior lamivudine resistance.
- TDF: caution with pre-existing renal dysfunction, low bone mineral density, or concurrent nephrotoxins — consider TAF instead.
- TAF: not recommended at eGFR < 15 mL/min without dialysis; more limited pregnancy data than TDF.
- All NAs: risk of severe hepatitis flare on abrupt discontinuation — do not stop without specialist input and close monitoring.
- Screen for HIV before starting HBV monotherapy — undiagnosed HIV/HBV co-infection risks selecting HIV resistance.
Side effects
- TDF: nephrotoxicity (including proximal tubulopathy / Fanconi syndrome) and reduced bone mineral density; otherwise generally well tolerated.
- TAF: lower renal and bone toxicity; modest increases in lipids and weight reported.
- Entecavir: generally very well tolerated; headache, fatigue, and nausea are uncommon.
- Class-wide: theoretical lactic acidosis (rare); post-treatment ALT flares.
Monitoring on treatment
| Parameter | Baseline | On therapy |
|---|---|---|
| HBV DNA | Yes | Every 3–6 months until suppressed, then every 6–12 months |
| ALT / liver panel | Yes | Every 3–6 months |
| Renal function (Cr, eGFR), phosphate, urinalysis | Yes (mandatory before TDF) | Every 6–12 months; more often for TDF + risk factors |
| HBsAg / HBeAg / anti-HBe (quantitative HBsAg) | Yes | Every 6–12 months to assess seroconversion / loss |
| Bone density (DXA) | If risk factors | As clinically indicated (especially long-term TDF) |
| HCC surveillance (US ± AFP q6 months) | Yes if indicated | Ongoing per surveillance criteria — continue even if virally suppressed |
Treatment endpoints
The ideal endpoint of HBV therapy is functional cure — sustained HBsAg loss with undetectable HBV DNA — which is associated with improved clinical outcomes and durable viral suppression after treatment discontinuation. Achievable endpoints, and whether therapy can be stopped, vary according to HBeAg status (reflecting different phases of infection) and the presence of cirrhosis.
HBeAg-negative, non-cirrhotic
Treatment cessation may be considered after loss of HBsAg, or when quantitative HBsAg is < 100 IU/mL in Asian patients or < 1,000 IU/mL in White patients, followed by an additional 12 months of consolidation therapy. Although not part of current guideline recommendations, an anti-HBs level > 100 mIU/mL at the time of HBsAg loss has been associated with improved clinical outcomes and a lower risk of reverse HBV seroconversion.
HBeAg-positive, non-cirrhotic
Treatment cessation may be considered after HBeAg seroconversion, followed by an additional 12 months of consolidation therapy.
HBV-related cirrhosis
Patients with cirrhosis are generally recommended to continue antiviral therapy indefinitely until loss of HBsAg, regardless of HBeAg status.