BackgroundNotable advances have been made in immune checkpoint inhibitors (ICIs) for cancer treatment. However, the adverse effects of ICIs, especially hepatotoxicity, remain a challenging problem. Whether patients in hepatitis B virus (HBV)‐endemic areas are prone to developing hepatic adverse events during ICI treatment warrants further exploration.MethodsFrom 2014 to 2020, the data of all patients with cancer who received ICI treatment at Taipei Veterans General Hospital were retrospectively reviewed. The incidence of and risk factors for hepatic adverse events, including hepatitis flare, immune‐related hepatitis (irHepatitis) and HBV reactivation (HBVr), were analysed through a Cox proportional hazard regression model.ResultsA total of 1283 patients with cancer (190 hepatocellular carcinoma [HCC] patients and 1093 patients with non‐HCC malignancies) were eligible for analysis, of whom 283 (22.1%) were HBsAg‐positive. The incidence of hepatitis flare events of any grade was significantly higher in HCC patients than in non‐HCC patients (45.8% vs. 25.6%, p < 0.001). HCC and baseline alanine aminotransferase (ALT) > 40 U/L were independent risk factors for ≥ grade 3 hepatitis flare events. No difference was observed in irHepatitis risk between HCC patients and non‐HCC patients. ALT > 40 U/L was an independent risk factor for irHepatitis. Among 283 HBsAg‐positive patients, six patients (2.1%) experienced HBVr. HCC patients had a higher risk of HBVr than non‐HCC patients (4.4% vs. 0.6%). No specific risk factor for HBVr could be identified. However, none of the patients under nucleos/tide analogue (NUC) prophylaxis experienced HBVr in this study.ConclusionsUnder ICI treatment, HCC patients had a higher risk of hepatitis flare events than non‐HCC patients. Abnormal baseline ALT levels are a risk factor for hepatic adverse events. NUC prophylaxis can minimise the risk of HBVr.

中文翻译：

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乙型肝炎流行地区肝脏和非肝脏恶性肿瘤免疫检查点抑制剂治疗期间的肝脏事件


背景用于癌症治疗的免疫检查点抑制剂 （ICI） 已取得显着进展。然而，ICIs 的不良反应，尤其是肝毒性，仍然是一个具有挑战性的问题。乙型肝炎病毒 （HBV） 流行地区的患者在 ICI 治疗期间是否容易发生肝脏不良事件，值得进一步探讨。方法回顾性分析2014—2020年在台北荣民总医院接受ICI治疗的所有癌症患者的资料。通过 Cox 比例风险回归模型分析肝脏不良事件的发生率和危险因素，包括肝炎发作、免疫相关肝炎 （irHepatitis） 和 HBV 再激活 （HBVr）。结果共有 1283 例癌症患者 （190 例肝细胞癌 [HCC] 患者和 1093 例非 HCC 恶性肿瘤患者）符合分析条件，其中 283 例 （22.1%） 为 HBsAg 阳性。HCC 患者任何级别肝炎发作事件的发生率均显著高于非 HCC 患者 （45.8% vs. 25.6%，p < 0.001）。HCC 和基线丙氨酸氨基转移酶 （ALT） > 40 U/L 是 ≥ 级肝炎发作事件的独立危险因素。在 HCC 患者和非 HCC 患者之间未观察到 irHepatitis 风险差异。ALT > 40 U/L 是 irHepatity 的独立危险因素。在 283 例 HBsAg 阳性患者中，6 例患者 （2.1%） 经历了 HBVr。HCC 患者发生 HBVr 的风险高于非 HCC 患者 （4.4% vs. 0.6%）。无法确定 HBVr 的特定危险因素。然而，在本研究中，接受核/潮汐类似物 （NUC） 预防的患者均未出现 HBVr。结论在 ICI 治疗下，HCC 患者发生肝炎发作事件的风险高于非 HCC 患者。 异常基线 ALT 水平是肝脏不良事件的危险因素。NUC 预防可以最大限度地降低 HBVr 的风险。