替諾福韋與恩替卡韋治療慢性乙型肝炎的肝細胞癌發生率：

StephenW

Hepatocellular carcinoma incidence with tenofovir versus entecavir in chronic hepatitis B: a systematic review and meta-analysis

Hepatocellular carcinoma incidence with tenofovir versus entecavir in chronic hepatitis B: a systematic review and meta-analysis

    Cheng-Hao Tseng, MD †
    Yao-Chun Hsu, MD †
    Tzu-Haw Chen, MD
    Fanpu Ji, MD
    I-Sung Chen, MD
    Ying-Nan Tsai, MD
    et al.
   

Published:September 29, 2020DOI:https://doi.org/10.1016/S2468-1253(20)30249-1

Summary
Background
It is unclear whether tenofovir disoproxil fumarate and entecavir differ in their association with risk of hepatocellular carcinoma in patients with chronic hepatitis B, and previous meta-analyses have shown conflicting conclusions with substantial heterogeneity. We aimed to analyse the updated data and elucidate the source of heterogeneity.
Methods
We searched PubMed, Embase, Web of Science, and the Cochrane library for relevant studies with time-to-event data for incident hepatocellular carcinoma occurring in patients with chronic hepatitis B who received tenofovir disoproxil fumarate or entecavir monotherapy with follow-up of at least 1 year. Studies published between Jan 1, 2006, and April 17, 2020, and abstracts from international conferences in 2018 and 2019 were included. We pooled covariate adjusted hazard ratios (HRs) for hepatocellular carcinoma using a random-effects model, assessed heterogeneity among included studies using the I 2 statistic and Cochran's Q test, and identified the source of heterogeneity using prespecified subgroup analyses. This study is registered with PROSPERO, ID CRD42020176513.
Findings
31 studies involving 119 053 patients were analysed. The 5-year cumulative incidence of hepatocellular carcinoma was 5·97% (95% CI 5·81–6·13, 28 studies) for entecavir and 3·06% (2·86–3·26, 13 studies) for tenofovir disoproxil fumarate in studies with unmatched populations (p<0·0001). For all eight studies matched by propensity score, the 5-year cumulative incidence was 3·44% (95% CI 3·08–3·80) for entecavir and 3·39% (2·94–3·83) for tenofovir disoproxil fumarate (p=0·87). Analysis of 14 comparative studies with covariate adjustment found that tenofovir disoproxil fumarate and entecavir had similar risk of hepatocellular carcinoma (primary outcome); adjusted HR 0·88, 95% CI 0·73–1·07; p=0·20), although heterogeneity was significant ( I 2=56·4%, p=0·0038). In a subgroup analysis for hospital-based clinical cohorts, there was no difference in hepatocellular carcinoma incidence between the two regimens (adjusted HR 1·03, 95% CI 0·88–1·21; I 2=0%). However, tenofovir disoproxil fumarate was associated with a lower risk of hepatocellular carcinoma compared with entecavir in administrative database research (adjusted HR 0·67, 0·59–0·76; I 2=0%).
Interpretation
Our study found no significant difference between tenofovir disoproxil fumarate and entecavir in their association with incident hepatocellular carcinoma. We suggest that treatment should be guided by patient tolerability and affordability rather than whether one drug is more effective than the other.
Funding
Supported in part by E-DA Hospital (EDAHP 106008; EDAHP 103046).

StephenW

替諾福韋與恩替卡韋治療慢性乙型肝炎的肝細胞癌發生率：系統評價和薈萃分析

替諾福韋與恩替卡韋治療慢性乙型肝炎的肝細胞癌發生率：系統評價和薈萃分析

    曾成浩，醫學博士†
    徐耀春，醫學博士†
    陳子虎醫師
    吉凡普醫學博士
    陳宜成醫師
    蔡英楠醫師
    等。
   

發佈時間：2020年9月29日DOI：https：//doi.org/10.1016/S2468-1253（20）30249-1

概要
背景
目前尚不清楚替諾福韋酯富馬酸酯和富馬酸恩替卡韋在慢性乙型肝炎患者中與肝細胞癌風險的相關性是否不同，並且先前的薈萃分析已顯示出結論不一致，且異質性很大。我們旨在分析更新的數據並闡明異質性的來源。
方法
我們在PubMed，Embase，Web of Science和Cochrane庫中搜索了有關事件發生時間數據的相關研究，以研究接受替諾福韋酯富馬酸酯或恩替卡韋單藥治療且至少隨訪至少20個月的慢性乙型肝炎患者發生的肝細胞事件1年。研究包括2006年1月1日至2020年4月17日之間發表的研究，以及2018年和2019年國際會議的摘要。我們使用隨機效應模型匯總了肝細胞癌的協變量調整風險比（HR），使用I 2統計量和Cochran Q檢驗評估了納入研究之間的異質性，並使用預先指定的亞組分析確定了異質性的來源。該研究已在PROSPERO註冊，ID為CRD42020176513。
發現
分析了涉及119-053名患者的31項研究。恩替卡韋的肝細胞癌5年累積發生率是5·97％（95％CI 5·81–6·13，28個研究），替諾福韋是3·06％（2·86–3·26，13個研究）人口不匹配的研究中存在富馬酸二甲吡酯（p <0·0001）。對於所有8項與傾向評分匹配的研究，恩替卡韋和替諾福韋的5年累積發生率分別為3·44％（95％CI 3·08–3·80）和3·39％（2·94–3·83）富馬酸吡索非爾（p = 0·87）。通過協變量調整對14項比較研究進行的分析發現，替諾福韋富馬酸替索羅非酯和恩替卡韋具有類似的肝細胞癌風險（主要結局）；調整後的HR 0·88，95％CI 0·73-1·07； p = 0·20），儘管異質性很明顯（I 2 = 56·4％，p = 0·0038）。在基於醫院的臨床隊列的亞組分析中，兩種方案之間的肝細胞癌發生率沒有差異（校正後的HR 1·03，95％CI 0·88-1·21； I 2 = 0％）。但是，在行政數據庫研究中，與恩替卡韋相比，替諾福韋酯富馬酸地索羅非酯與肝細胞癌的風險較低（校正後的HR 0·67、0·59-0·76； I 2 = 0％）。
解釋
我們的研究發現替諾福韋富馬酸替諾福韋酯和恩替卡韋與肝細胞癌的發病率之間無顯著差異。我們建議治療應以患者的耐受性和負擔能力為指導，而不是一種藥物是否比另一種藥物更有效。
資金
由E-DA醫院（EDAHP 106008; EDAHP 103046）部分支持