Version July 2025
| Pegylated IFN-alfa-2a[1] | Entecavir* | Tenofovir (TDF or TAF) | |
| Duration of treatment | 48 weeks | >1 year¶ | >1 year¶ |
| Age group (based on FDA approval) | ≥3 years | ≥2 years | ≥2 years (for TDF) ≥6 years (for TAF) |
| Route | Subcutaneous | Oral | Oral |
| Side effectsΔ | Flu-like symptoms (mostly with initial doses), mood/behavior disturbances, cytopenias, anorexia, growth attenuation or weight loss, increases in serum ALT (common) accompanied by hepatic decompensation (rare) | Generally mild (but lactic acidosis can occur in decompensated cirrhosis) | TDF – Potential nephrotoxicity, reduced bone mineral density TAF – Adverse effects on kidney and bone are less common |
| Relative contraindications | Underlying autoimmune disorder, organ transplant, decompensated liver disease, serious neuropsychiatric disease | Previous exposure to lamivudine | None |
| Drug resistance◊ | None | Approximately 1% up to year 6 | None |
ALT: alanine aminotransferase; anti-HBe: antibody to HBeAg; FDA: US Food and Drug Administration; HBeAg: hepatitis B e-antigen; IFN-alfa: interferon alfa; TAF: tenofovir alafenamide; TDF: tenofovir disoproxil fumarate.
* Entecavir is a first-line option for treatment-naïve patients but not for those with lamivudine resistance. Among patients who are resistant to lamivudine who switch to entecavir, up to 50% develop resistance to entecavir within 5 years (based on adult data)[2].
¶ For patients without cirrhosis who are treated with nucleos(t)ide analogs, treatment should continue for at least 12 months after seroconversion from HBeAg to anti-HBe. Many clinicians recommend continuing treatment indefinitely, unless the patient clears HBsAg. For patients with cirrhosis, these drugs generally should be continued indefinitely, unless they clear HBsAg. For all nucleos(t)ide analogs, patients are at risk for exacerbations of hepatitis B after discontinuation of treatment. Patients who stop antiviral therapy should be monitored closely for evidence of disease reactivation.
Δ This is not a complete list of side effects. Refer to drug information monographs included within UpToDate and local prescribing information for more detail.
◊ Data about drug resistance are based primarily on studies in adults.