Hung Yi-Ping, Lee Pei-Chang, Chang Yen-Hwa, Yang Muh-Hwa, Chiu Chao-Hua, Chen Ming-Huang, Lan Keng-Hsin, Lee I-Cheng, Hou Ming-Chih, Chao Yee, Huang Yi-Hsiang
Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Aliment Pharmacol Ther. 2025 Feb;61(3):501-512. doi: 10.1111/apt.18403. Epub 2024 Nov 24.
Notable 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.
From 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.
A 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.
Under 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.
免疫检查点抑制剂（ICI）在癌症治疗方面取得了显著进展。然而，ICI的不良反应，尤其是肝毒性，仍然是一个具有挑战性的问题。在乙型肝炎病毒（HBV）流行地区，患者在ICI治疗期间是否更容易发生肝脏不良事件值得进一步探索。
回顾性分析2014年至2020年在台北荣民总医院接受ICI治疗的所有癌症患者的数据。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）。
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患者任何级别的肝炎发作事件发生率均显著高于非HCC患者（45.8%对25.6%，p<0.001）。HCC和基线丙氨酸氨基转移酶（ALT）>40 U/L是≥3级肝炎发作事件的独立危险因素。HCC患者和非HCC患者的irHepatitis风险无差异。ALT>40 U/L是irHepatitis的独立危险因素。在283例HBsAg阳性患者中，6例（2.1%）发生了HBVr。HCC患者的HBVr风险高于非HCC患者（4.4%对0.6%）。未发现HBVr的特定危险因素。然而，在本研究中，接受核苷/核苷酸类似物（NUC）预防的患者均未发生HBVr。
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。基线ALT水平异常是肝脏不良事件的危险因素。NUC预防可将HBVr风险降至最低。
