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Introduction <p>Oral nucleos(t)ide analogues (NAs) are widely used in managing hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Among first-line therapies, entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are commonly prescribed. However, their comparative efficacy and safety remain unclear in HBV-ACLF.</p> Methods <p>We performed a systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to January 2025 for studies evaluating ETV, TDF, and TAF in HBV-ACLF. The data were analyzed using standardized mean differences (SMD), 95% confidence intervals (95% CI), and surface under the cumulative ranking curve (SUCRA).</p> Results <p>Nine studies (five prospective, four retrospective) were included. TDF significantly improved 12-week survival compared to ETV (SMD = −&#xa0;0.21; 95% CI −&#xa0;0.36 to −&#xa0;0.06), with no significant difference between TDF and TAF. For 12-week HBV-DNA clearance, TAF outperformed ETV (SMD = −&#xa0;0.40; 95% CI −&#xa0;0.77 to −&#xa0;0.02), ranking highest in SUCRA (83.5%). TAF also showed superior virological suppression at 4&#xa0;weeks (SUCRA: TAF 72.2% &gt; ETV 49.1% &gt; TDF 28.8%). TDF improved 12-week model for end-stage liver disease (MELD) scores more than ETV (SMD = 1.05; 95% CI 0.15–1.94). The drugs did not differ significantly in improving liver function at 4&#xa0;weeks, as measured by alanine aminotransferase (ALT) and total bilirubin (TBIL) levels. Regarding renal function, ETV had a greater impact on the 4-week estimated glomerular filtration rate (eGFR) than TAF (SMD = −&#xa0;0.35; 95% CI −&#xa0;0.52 to 0.18), and both TDF and ETV showed a more significant effect on the 4-week creatinine (cr) levels than TAF (TDF: SMD = 0.29; 95% CI 0.00–0.57; ETV: SMD = 0.30; 95% CI 0.09–0.51).</p> Conclusions <p>Overall, TDF and TAF provide superior survival and antiviral benefits over ETV in HBV-ACLF, with three drugs showing similar effects in improving liver function. Moreover, TAF demonstrated the most favorable profile in viral suppression and renal safety.</p>

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Efficacy and Safety of Entecavir, Tenofovir Disoproxil Fumarate, and Tenofovir Alafenamide Fumarate in Treating Acute-on-Chronic Liver Failure with Hepatitis B Virus: A Network Meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月3日

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  • Jia Liu,
  • Yanzhen Bi,
  • Xuefeng Ma,
  • Yongning Xin

摘要

Introduction

Oral nucleos(t)ide analogues (NAs) are widely used in managing hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). Among first-line therapies, entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are commonly prescribed. However, their comparative efficacy and safety remain unclear in HBV-ACLF.

Methods

We performed a systematic search of PubMed, Embase, Cochrane Library, and Web of Science up to January 2025 for studies evaluating ETV, TDF, and TAF in HBV-ACLF. The data were analyzed using standardized mean differences (SMD), 95% confidence intervals (95% CI), and surface under the cumulative ranking curve (SUCRA).

Results

Nine studies (five prospective, four retrospective) were included. TDF significantly improved 12-week survival compared to ETV (SMD = − 0.21; 95% CI − 0.36 to − 0.06), with no significant difference between TDF and TAF. For 12-week HBV-DNA clearance, TAF outperformed ETV (SMD = − 0.40; 95% CI − 0.77 to − 0.02), ranking highest in SUCRA (83.5%). TAF also showed superior virological suppression at 4 weeks (SUCRA: TAF 72.2% > ETV 49.1% > TDF 28.8%). TDF improved 12-week model for end-stage liver disease (MELD) scores more than ETV (SMD = 1.05; 95% CI 0.15–1.94). The drugs did not differ significantly in improving liver function at 4 weeks, as measured by alanine aminotransferase (ALT) and total bilirubin (TBIL) levels. Regarding renal function, ETV had a greater impact on the 4-week estimated glomerular filtration rate (eGFR) than TAF (SMD = − 0.35; 95% CI − 0.52 to 0.18), and both TDF and ETV showed a more significant effect on the 4-week creatinine (cr) levels than TAF (TDF: SMD = 0.29; 95% CI 0.00–0.57; ETV: SMD = 0.30; 95% CI 0.09–0.51).

Conclusions

Overall, TDF and TAF provide superior survival and antiviral benefits over ETV in HBV-ACLF, with three drugs showing similar effects in improving liver function. Moreover, TAF demonstrated the most favorable profile in viral suppression and renal safety.