Background: Recent studies suggested that use of antibiotics may interfere with treatment responses to immune checkpoint inhibitors (ICIs). We determined whether concurrent use of antibiotics during ICI therapy was associated with adverse outcomes in patients with advanced hepatocellular carcinoma (HCC). Methods: This is a territory-wide retrospective cohort study including all advanced HCC patients who received ICIs (nivolumab, pembrolizumab, or ipilimumab) between January 2014 and December 2019. Exclusion criteria included prior liver transplantation and use of cabozantinib, regorafenib, or ramucirumab. The exposure of interest was concurrent antibiotic use within 30 days before or after the commencement of ICI. The adjusted hazard ratio (aHR) of cancer-related mortality and all-cause mortality with antibiotic use was derived by propensity score (PS) matching in 1:2 ratio of covariates including baseline characteristics, causes of cirrhosis, Child-Pugh status, prior HCC treatment, comorbidities, concurrent medications, and laboratory results including alpha fetoprotein. Results: A total of 395 HCC patients who had received ICIs were included. During a median follow-up of 16.5 months (interquartile range [IQR]: 5.6–44.3), there were 286 (72.4%) deaths including 231 cancer-related deaths. The median time from the first ICI to event was 7.7 months (IQR: 4.0–16.8). PS matching of 56 antibiotic users with 99 nonusers showed that concurrent antibiotic use with ICI was associated with higher cancer-related (aHR: 1.66; 95% CI: 1.08–2.54) and all-cause mortality (aHR: 1.63; 95% CI: 1.17–2.28). Conclusions: Concurrent antibiotic use during immunotherapy was associated with higher mortality in patients with advanced HCC. Further studies should examine the role of gut dysbiosis on responses to ICI.
Liver Cancer

中文翻译：

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免疫检查点抑制剂治疗期间抗生素的使用与肝细胞癌的较低生存率有关

背景：最近的研究表明，使用抗生素可能会干扰对免疫检查点抑制剂 (ICI) 的治疗反应。我们确定了在 ICI 治疗期间同时使用抗生素是否与晚期肝细胞癌 (HCC) 患者的不良结局相关。方法：这是一项全港性回顾性队列研究，包括所有在 2014 年 1 月至 2019 年 12 月期间接受 ICI（纳武单抗、派姆单抗或伊匹单抗）的晚期 HCC 患者。排除标准包括既往肝移植和使用卡博替尼、瑞戈非尼或雷莫芦单抗。感兴趣的暴露是在 ICI 开始之前或之后 30 天内同时使用抗生素。癌症相关死亡率和抗生素使用全因死亡率的调整风险比 (aHR) 是通过倾向评分 (PS) 以 1:2 的协变量比率匹配得出的，包括基线特征、肝硬化原因、Child-Pugh 状态、既往HCC 治疗、合并症、并发药物治疗和包括甲胎蛋白在内的实验室结果。结果：共纳入 395 名接受过 ICI 的 HCC 患者。在 16.5 个月的中位随访期间（四分位距 [IQR]：5.6-44.3），共有 286 人（72.4%）死亡，其中 231 人死于癌症。从第一次 ICI 到事件的中位时间为 7.7 个月（IQR：4.0-16.8）。56 名抗生素使用者与 99 名非使用者的 PS 匹配表明，同时使用抗生素与 ICI 与更高的癌症相关（aHR：1.66；95% CI：1.08-2.54）和全因死亡率（aHR：1.63；95% CI： 1.17-2.28）。结论：免疫治疗期间同时使用抗生素与晚期 HCC 患者较高的死亡率相关。进一步的研究应该检查肠道菌群失调对 ICI 反应的作用。
肝癌