Evidence map›Paper›PMID 42919405›Full record

SynthesisVirology journal2026

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.

Shuqi Yang, Yijie Lin, Wenjin Yuan, Yanlan Liang, Huatang Zhang, Xing Wang, Jiaxuan Li, Wenwu Lin, Wencong Hong, Zhijun Su and 1 more

Abstract readSystematic ReviewMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Virology journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Shuqi Yang *Department of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital, Quanzhou, 362000, China.
Yijie Lin *Department of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital, Quanzhou, 362000, China.
Wenjin YuanDepartment of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital, Quanzhou, 362000, China.
Yanlan LiangDepartment of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital, Quanzhou, 362000, China.
Huatang ZhangDepartment of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital, Quanzhou, 362000, China.
Xing WangDepartment of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital, Quanzhou, 362000, China.
Jiaxuan LiThe School of Clinical Medicine, Fujian Medical University, Fuzhou, 350122, China.
Wenwu LinDepartment of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital, Quanzhou, 362000, China.
Wencong HongDepartment of Respiratory and Critical Care Medicine, Nan 'an Hospital, Quanzhou, 362000, China.
Zhijun SuDepartment of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital, Quanzhou, 362000, China. su2366@sina.com.
Xueping YuDepartment of Infection Disease, Clinical Medical Research Center for Bacterial an d Fungal Infectious Diseases of Fujian province, Fujian Medical University Affiliated First Quanzhou hospital, Quanzhou, 362000, China. xpyu15@fudan.edu.cn.

Funding

Major Science and Technology innovation Project of Fujian Province 2023Y9269National Natural Science Foundation of China 82570707Natural Science Foundation of Fujian Province 2023J01239
6 · The paper itself

Abstract

backgroundWhether tenofovir disoproxil fumarate (TDF) or entecavir (ETV) combined with pegylated interferon offers superior functional cure potential in chronic hepatitis B remains unclear.

objectiveTo compare the efficacy and safety of TDF plus interferon versus ETV plus interferon against their respective monotherapies.

methodsSystematic review and meta-analysis of 16 randomized controlled trials from six databases (inception to January 2026).

interventionsTDF (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.

results2,575 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.

conclusionsTDF-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.

Indexed as

Antiviral AgentsGuanineHepatitis B, ChronicInterferon-alphaTenofovirDrug Therapy, CombinationHepatitis B e AntigensHumansPolyethylene GlycolsRandomized Controlled Trials as TopicRecombinant ProteinsTreatment OutcomeAntiviral AgentsentecavirGuanineHepatitis B e AntigensInterferon-alphapeginterferon alfa-2aPolyethylene GlycolsRecombinant ProteinsTenofovirChronic hepatitis BEntecavirFunctional cureMeta-analysisPegylated interferonTenofovir disoproxil fumarate

Identifiers

PMID42919405

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.