Efficacy and safety of Tenofovir disoproxil fumarate (TDF) or Entecavir (ETV) combined with interferon for the treatment of chronic hepatitis B: a systematic review and meta-analysis
- 1Department of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital
- 2The School of Clinical Medicine, Fujian Medical University
- 3Department of Respiratory and Critical Care Medicine, Nan ’an Hospital
Abstract
Background Whether tenofovir disoproxil fumarate (TDF) or entecavir (ETV) combined with pegylated interferon offers superior functional cure potential in chronic hepatitis B remains unclear. Objective To compare the efficacy and safety of TDF plus interferon versus ETV plus interferon against their respective monotherapies. Methods Systematic review and meta-analysis of 16 randomized controlled trials from six databases (inception to January 2026). Interventions: TDF (300 mg/day) or ETV (0.5 mg/day) plus pegylated interferon alfa-2a/2b (180 µg/week) versus monotherapy. Primary outcomes: HBsAg reduction and HBeAg seroconversion. Risk of bias: Cochrane RoB 2; Certainty: GRADE. PROSPERO: CRD42025632412. Results 2,575 patients were included. TDF plus interferon achieved markedly superior HBsAg reduction versus TDF monotherapy (OR 5.16, 95% CI 2.71–9.84; ARD 4.9%, 95% CI 2.0–9.9; NNT 20, 95% CI 10–50), whereas ETV plus interferon showed no significant benefit (OR 1.16, 95% CI 0.56–2.40; P = 0.006 for interaction). HBeAg seroconversion similarly favored TDF-based regimens (OR 2.25 vs. 1.63). HBV DNA negativity improved overall, although this effect was confined to TDF-based regimens. Safety data were highly heterogeneous (I² > 80% within both regimen subgroups) and derived from variable reporting standards; no reliable pooled estimate was constructed. Descriptive synthesis revealed no consistent excess toxicity for TDF-based or ETV-based combinations, though certainty remains very low. Sensitivity analyses excluding high-risk trials demonstrated robustness. GRADE certainty: moderate for serological outcomes, low for HBV DNA, very low for safety. Conclusions TDF-based combination regimens were associated with superior functional cure potential compared with ETV-based alternatives, suggesting a potential efficacy hierarchy that prior pooled analyses obscured. TDF may represent a potential backbone option for patients seeking HBsAg loss, with ETV combinations remaining an appropriate alternative, particularly for those with TDF contraindications or baseline renal impairment or osteopenia. However, these findings are descriptive rather than prescriptive, derive specifically from predominantly HBeAg-positive Asian populations, and should not be generalized to other demographic or disease-stage groups without further validation. The moderate-to-low certainty of evidence, substantial methodological limitations, lack of blinded trials, and insufficient safety data to exclude differential renal or bone toxicity between backbones preclude definitive treatment recommendations. Confirmation in double-blind trials is needed.
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BibTeX
@article{yang2026efficacy,
title = {{Efficacy and safety of Tenofovir disoproxil fumarate (TDF) or Entecavir (ETV) combined with interferon for the treatment of chronic hepatitis B: a systematic review and meta-analysis}},
author = {Shuqi Yang and Yijie Lin and Wenjin Yuan and Yanlan Liang and Huatang Zhang and Xing Wang and Jiaxuan Li and Wenwu Lin and Wencong Hong and Zhijun Su and Xueping Yu},
journal = {Virology Journal},
year = {2026},
month = jul,
doi = {10.1186/s12985-026-03254-7},
url = {https://doi.org/10.1186/s12985-026-03254-7},
note = {CC BY},
}
RIS
TY - JOUR
TI - Efficacy and safety of Tenofovir disoproxil fumarate (TDF) or Entecavir (ETV) combined with interferon for the treatment of chronic hepatitis B: a systematic review and meta-analysis
AU - Shuqi Yang
AU - Yijie Lin
AU - Wenjin Yuan
AU - Yanlan Liang
AU - Huatang Zhang
AU - Xing Wang
AU - Jiaxuan Li
AU - Wenwu Lin
AU - Wencong Hong
AU - Zhijun Su
AU - Xueping Yu
PY - 2026
DA - 2026/07/01
JO - Virology Journal
DO - 10.1186/s12985-026-03254-7
UR - https://doi.org/10.1186/s12985-026-03254-7
AB - Background Whether tenofovir disoproxil fumarate (TDF) or entecavir (ETV) combined with pegylated interferon offers superior functional cure potential in chronic hepatitis B remains unclear. Objective To compare the efficacy and safety of TDF plus interferon versus ETV plus interferon against their respective monotherapies. Methods Systematic review and meta-analysis of 16 randomized controlled trials from six databases (inception to January 2026). Interventions: TDF (300 mg/day) or ETV (0.5 mg/day) plus pegylated interferon alfa-2a/2b (180 µg/week) versus monotherapy. Primary outcomes: HBsAg reduction and HBeAg seroconversion. Risk of bias: Cochrane RoB 2; Certainty: GRADE. PROSPERO: CRD42025632412. Results 2,575 patients were included. TDF plus interferon achieved markedly superior HBsAg reduction versus TDF monotherapy (OR 5.16, 95% CI 2.71–9.84; ARD 4.9%, 95% CI 2.0–9.9; NNT 20, 95% CI 10–50), whereas ETV plus interferon showed no significant benefit (OR 1.16, 95% CI 0.56–2.40; P = 0.006 for interaction). HBeAg seroconversion similarly favored TDF-based regimens (OR 2.25 vs. 1.63). HBV DNA negativity improved overall, although this effect was confined to TDF-based regimens. Safety data were highly heterogeneous (I² > 80% within both regimen subgroups) and derived from variable reporting standards; no reliable pooled estimate was constructed. Descriptive synthesis revealed no consistent excess toxicity for TDF-based or ETV-based combinations, though certainty remains very low. Sensitivity analyses excluding high-risk trials demonstrated robustness. GRADE certainty: moderate for serological outcomes, low for HBV DNA, very low for safety. Conclusions TDF-based combination regimens were associated with superior functional cure potential compared with ETV-based alternatives, suggesting a potential efficacy hierarchy that prior pooled analyses obscured. TDF may represent a potential backbone option for patients seeking HBsAg loss, with ETV combinations remaining an appropriate alternative, particularly for those with TDF contraindications or baseline renal impairment or osteopenia. However, these findings are descriptive rather than prescriptive, derive specifically from predominantly HBeAg-positive Asian populations, and should not be generalized to other demographic or disease-stage groups without further validation. The moderate-to-low certainty of evidence, substantial methodological limitations, lack of blinded trials, and insufficient safety data to exclude differential renal or bone toxicity between backbones preclude definitive treatment recommendations. Confirmation in double-blind trials is needed.
SN - 1743-422X
ER -