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.

IF 5.3 3区医学 Q1 INFECTIOUS DISEASES

Infectious Diseases and Therapy Pub Date : 2025-10-01 Epub Date: 2025-09-03 DOI:10.1007/s40121-025-01212-4

Jia Liu, Yanzhen Bi, Xuefeng Ma, Yongning Xin

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引用次数: 0

Abstract

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.

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恩替卡韦、富马酸替诺福韦二奥proxil和富马酸替诺福韦Alafenamide治疗急性慢性乙型肝炎病毒肝衰竭的疗效和安全性：一项网络荟萃分析

口服核苷类似物（NAs）广泛用于治疗乙型肝炎病毒相关的急性-慢性肝衰竭（HBV-ACLF）。在一线治疗中，恩替卡韦（ETV）、富马酸替诺福韦二吡酯（TDF）和替诺福韦阿拉芬胺（TAF）是常用的处方。然而，它们在HBV-ACLF中的相对疗效和安全性仍不清楚。方法：我们系统检索了PubMed、Embase、Cochrane Library和Web of Science，检索了截至2025年1月评估HBV-ACLF中ETV、TDF和TAF的研究。采用标准化平均差（SMD）、95%置信区间（95% CI）和累积排序曲线下曲面（SUCRA）对数据进行分析。结果：纳入9项研究（5项前瞻性研究，4项回顾性研究）。与ETV相比，TDF显著提高了12周生存率（SMD = - 0.21; 95% CI - 0.36至- 0.06），TDF和TAF之间无显著差异。对于12周HBV-DNA清除率，TAF优于ETV (SMD = - 0.40; 95% CI - 0.77至- 0.02)，在SUCRA中排名最高（83.5%）。TAF在4周时也表现出优越的病毒学抑制（SUCRA: TAF 72.2% b> ETV 49.1% b> TDF 28.8%）。TDF改善终末期肝病（MELD） 12周模型评分高于ETV （SMD = 1.05; 95% CI 0.15-1.94）。通过测量丙氨酸转氨酶（ALT）和总胆红素（TBIL）水平，两种药物在改善4周肝功能方面没有显著差异。在肾功能方面，ETV对4周肾小球滤过率（eGFR）的影响大于TAF (SMD = - 0.35; 95% CI - 0.52 ~ 0.18)， TDF和ETV对4周肌酐（cr）水平的影响均大于TAF （TDF: SMD = 0.29; 95% CI 0.00 ~ 0.57; ETV: SMD = 0.30; 95% CI 0.09 ~ 0.51）。结论：总体而言，与ETV相比，TDF和TAF在HBV-ACLF患者中提供了更好的生存和抗病毒益处，三种药物在改善肝功能方面表现出相似的效果。此外，TAF在病毒抑制和肾脏安全方面表现出最有利的特征。

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来源期刊

Infectious Diseases and Therapy Medicine-Microbiology (medical)

CiteScore

8.60

自引率

1.90%

发文量

136

审稿时长

6 weeks

期刊介绍： Infectious Diseases and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of infectious disease therapies and interventions, including vaccines and devices. Studies relating to diagnostic products and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. Areas of focus include, but are not limited to, bacterial and fungal infections, viral infections (including HIV/AIDS and hepatitis), parasitological diseases, tuberculosis and other mycobacterial diseases, vaccinations and other interventions, and drug-resistance, chronic infections, epidemiology and tropical, emergent, pediatric, dermal and sexually-transmitted diseases.