Wang Wenjun, Lie Puyi, Guo Minzhang, He Jianxing
State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
Int J Cancer. 2017 Sep 1;141(5):1018-1028. doi: 10.1002/ijc.30678. Epub 2017 Jun 20.
Although existing evidence from clinical trials has demonstrated manifestation of hepatic adverse events with the use of immune checkpoint inhibitors (ICPIs), overall risks have yet to be reported. Therefore, we assessed the risk of hepatotoxicity associated with inhibitors of the immune checkpoint. We examined data from the Pubmed, Medline and Google Scholar databases. We also examined original studies and review articles for crossreferences Eligible studies included randomized Phase II to Phase III trials of cancer patients treated with nivolumab, pembrolizumab, ipilimumab, tremelimumab. The authors extracted relevant information on participants' characteristics, all-grade and high-grade hepatotoxicity and information on the methodology of the studies. In total, 17 trials were considered eligible for the meta-analysis. The odds ratio for all-grade hepatotoxicity for CTLA-4 inhibitors (Ipilimumab and tremelimumab) was 1.24 (95% confidence interval 0.75, 2.05; p = 0.39) and for high-grade hepatotoxicity was 1.93 (95% confidence interval 0.84, 4.44; p =0.12). Moreover, the odds ratio for all-grade hepatotoxicity for PD-1 inhibitors was 1.52 (95% confidence interval 1.24, 1.86; p < 0.0001) and for high-grade hepatotoxicity was 0.48 (95% confidence interval 0.29, 0.80; p =0.005). The analysis of data showed that CTLA-4 inhibitors seem to be associated with a higher risk of all- and high-grade hepatotoxicity compared with control regimens, whereas PD-1 inhibitors seem to be associated with a lower risk of all- and high-grade hepatotoxicity compared with control regimens.
尽管来自临床试验的现有证据已证明使用免疫检查点抑制剂（ICPI）会出现肝脏不良事件，但总体风险尚未见报道。因此，我们评估了与免疫检查点抑制剂相关的肝毒性风险。我们检索了PubMed、Medline和谷歌学术数据库中的数据。我们还查阅了原始研究和综述文章以进行交叉引用。符合条件的研究包括接受纳武单抗、帕博利珠单抗、伊匹木单抗、曲美木单抗治疗的癌症患者的随机II期至III期试验。作者提取了有关参与者特征、所有级别和高级别肝毒性以及研究方法的相关信息。总共有17项试验被认为符合荟萃分析的条件。CTLA-4抑制剂（伊匹木单抗和曲美木单抗）所有级别肝毒性的比值比为1.24（95%置信区间0.75，2.05；p = 0.39），高级别肝毒性的比值比为1.93（95%置信区间0.84，4.44；p = 0.12）。此外，PD-1抑制剂所有级别肝毒性的比值比为1.52（95%置信区间1.24，1.86；p < 0.0001），高级别肝毒性的比值比为0.48（95%置信区间0.29，0.80；p = 0.005）。数据分析表明，与对照方案相比，CTLA-4抑制剂似乎与所有级别和高级别肝毒性的较高风险相关，而与对照方案相比，PD-1抑制剂似乎与所有级别和高级别肝毒性的较低风险相关。
