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替诺福韦与恩替卡韦对慢性乙型肝炎病毒感染患者肝细胞癌风险的影响:一项系统评价和荟萃分析

Effects of Tenofovir vs Entecavir on Risk of Hepatocellular Carcinoma in Patients With Chronic HBV Infection: A Systematic Review and Meta-analysis.

作者信息

Choi Won-Mook, Choi Jonggi, Lim Young-Suk

机构信息

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

出版信息

Clin Gastroenterol Hepatol. 2021 Feb;19(2):246-258.e9. doi: 10.1016/j.cgh.2020.05.008. Epub 2020 May 11.

Abstract

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) and entecavir are recommended as first-line treatments for chronic hepatitis B virus (HBV) infection. However, there is debate over the comparative effectiveness of these drugs in preventing hepatocellular carcinoma (HCC). We performed a systematic review and meta-analysis of the effectiveness of TDF vs entecavir in reducing the incidence of HCC among patients with chronic HBV infection.

METHODS

We performed a systematic review of the MEDLINE, EMBASE, Web of Science, and Cochrane Library from 2010 through 2019 for full-text articles and conference abstracts on studies of effects of TDF vs entecavir in patients with HBV infection. Extracted data were analyzed with the random-effects model. Potential sources of heterogeneity were investigated using sensitivity, meta-regression, and subgroup analyses.

RESULTS

Our final analysis comprised 15 studies (61,787 patients; 16,101 patients given TDF and 45,686 given entecavir). TDF treatment was associated with a significantly lower risk of HCC than entecavir (hazard ratio, 0.80; 95% CI, 0.69-0.93; P = .003; I = 13%). The lower risk of HCC in patients given TDF compared with entecavir persisted in sensitivity and subcohort analyses performed with propensity score-matched cohorts and cirrhosis subcohorts. Inclusion of patients with decompensated cirrhosis and the sample size were the factors with the largest effects on between-study heterogeneity in meta-regression analyses. Subsequent subgroup analyses showed no statistical differences in the incidence of death or transplantation (hazard ratio, 0.93; 95% CI, 0.73-1.17; P = .519; I = 6%) between patients given TDF vs entecavir.

CONCLUSIONS

In a meta-analysis of studies of patients with chronic HBV infection, we found that TDF treatment was associated with a significantly lower (20%) risk of HCC than entecavir treatment. Randomized trials are needed to support this finding.

摘要

背景与目的

富马酸替诺福韦二吡呋酯(TDF)和恩替卡韦被推荐作为慢性乙型肝炎病毒(HBV)感染的一线治疗药物。然而,关于这些药物在预防肝细胞癌(HCC)方面的相对有效性存在争议。我们对TDF与恩替卡韦在降低慢性HBV感染患者HCC发生率方面的有效性进行了系统评价和荟萃分析。

方法

我们对2010年至2019年期间的MEDLINE、EMBASE、科学网和考克兰图书馆进行了系统检索,以获取关于TDF与恩替卡韦对HBV感染患者影响的研究的全文文章和会议摘要。提取的数据采用随机效应模型进行分析。使用敏感性分析、meta回归分析和亚组分析来研究异质性的潜在来源。

结果

我们的最终分析纳入了15项研究(61787例患者;16101例接受TDF治疗,45686例接受恩替卡韦治疗)。与恩替卡韦相比,TDF治疗与显著更低的HCC风险相关(风险比,0.80;95%置信区间,0.69 - 0.93;P = 0.003;I² = 13%)。在使用倾向评分匹配队列和肝硬化亚队列进行的敏感性分析和亚队列分析中,接受TDF治疗的患者与接受恩替卡韦治疗的患者相比,HCC风险更低这一结果仍然成立。纳入失代偿期肝硬化患者和样本量是meta回归分析中对研究间异质性影响最大的因素。随后的亚组分析显示,接受TDF治疗与接受恩替卡韦治疗的患者在死亡或移植发生率方面无统计学差异(风险比,0.93;95%置信区间,0.73 - 1.17;P = 0.519;I² = 6%)。

结论

在一项对慢性HBV感染患者研究的荟萃分析中,我们发现与恩替卡韦治疗相比,TDF治疗与显著更低(20%)的HCC风险相关。需要进行随机试验来支持这一发现。

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