双重检查点抑制剂引起的重度肝毒性在肝细胞癌中比在其他癌症中更常见。
High Grade Hepatotoxicity From Dual Checkpoint Inhibitors Is More Common in Hepatocellular Carcinoma Than Other Cancers.
作者信息
Ennin Elsie, Mallepally Niharika, Ali Myra, Shojaie Layla, Dewberry Sean, Trieu Melissa, Torres Evanthia T Roussos, Zhou Kali, Kahn Jeffrey, Dodge Jennifer L, Dara Lily
机构信息
Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at University of California, Los Angeles, California, USA.
出版信息
Liver Int. 2025 Sep;45(9):e70255. doi: 10.1111/liv.70255.
BACKGROUND & AIMS: Immune checkpoint inhibitors (ICIs) are therapy for many malignancies including hepatocellular carcinoma (HCC), yet the impact of HCC on immune-mediated liver injury from checkpoint inhibitors (ILICI) remains poorly understood and no direct comparison exists for hepatotoxicity rates between ICI and sorafenib in HCC.
METHODS
In this retrospective cohort study, we extracted data on adult patients treated with five ICI regimens for HCC or non-HCC cancers, and HCC patients who received sorafenib between 2010 and 2020. The primary outcome was grade ≥ 3 ILICI or sorafenib (DILI). Logistic regression estimated adjusted odds ratios (OR) for liver injury.
RESULTS
We identified 530 patients, 129 (24%) HCC-ICI, 256 (48%) non-HCC ICI, and 145 (27%) HCC-sorafenib. Compared to non-HCC ICI, HCC-ICI and HCC-sorafenib were more often male (57%, 82%, 77%), Hispanic (14%, 35%, 34%), and cirrhotic (1%, 85%, 88%). Twenty-three patients developed grade ≥ 3 ILICI. ILICI incidence was higher for HCC-ICI (11%, CI 6-18) versus non-HCC ICI (4%, CI 2-6, p = 0.006) and DILI in HCC-sorafenib (3%, CI 1-8, p = 0.02) with incidence highest for ipilimumab-nivolumab (HCC-ICI 42%, CI 15-72 versus non-HCC 10%, CI 3-24; p = 0.02). On multivariable regression, ILICI was associated with HCC (OR 4.5, CI 1.8-11.4, p = 0.002) and treatment with ipilimumab-nivolumab (OR 6.9, CI 2.6-18.3, p < 0.001). Incidence of liver injury in HCC remained elevated for ICI versus sorafenib (OR 3.5, CI 1.2-10.4, p = 0.02).
CONCLUSIONS
We identified an elevated risk of liver injury in HCC patients receiving ICIs compared to ICI-treated non-HCC cancers and sorafenib-treated HCC, with dual ipilimumab-nivolumab therapy carrying the highest risk.
背景与目的
免疫检查点抑制剂（ICI）是用于治疗包括肝细胞癌（HCC）在内的多种恶性肿瘤的疗法，但HCC对检查点抑制剂引起的免疫介导性肝损伤（ILICI）的影响仍知之甚少，且在HCC中，ICI与索拉非尼之间的肝毒性发生率尚无直接比较。
方法
在这项回顾性队列研究中，我们提取了接受五种ICI方案治疗HCC或非HCC癌症的成年患者，以及2010年至2020年间接受索拉非尼治疗的HCC患者的数据。主要结局是≥3级的ILICI或索拉非尼（药物性肝损伤，DILI）。逻辑回归估计肝损伤的调整比值比（OR）。
结果
我们确定了530例患者，其中129例（24%）为HCC-ICI，256例（48%）为非HCC-ICI，145例（27%）为HCC-索拉非尼。与非HCC-ICI相比，HCC-ICI和HCC-索拉非尼患者男性比例更高（分别为57%、82%、77%），西班牙裔比例更高（分别为14%、35%、34%），肝硬化比例更高（分别为1%、85%、88%）。23例患者发生了≥3级的ILICI。HCC-ICI的ILICI发生率高于非HCC-ICI（11%，CI 6-18）（4%，CI 2-6，p=0.006），HCC-索拉非尼的DILI发生率为3%（CI 1-8，p=0.02），其中伊匹木单抗-纳武单抗的发生率最高（HCC-ICI为42%，CI 15-72；非HCC为10%，CI 3-24；p=0.02）。在多变量回归中，ILICI与HCC相关（OR 4.5，CI 1.8-11.4，p=0.002），以及与伊匹木单抗-纳武单抗治疗相关（OR 6.9，CI 2.6-18.3，p<0.001）。与索拉非尼相比，ICI治疗的HCC患者肝损伤发生率仍然较高（OR 3.5，CI 1.2-10.4，p=0.02）。
结论
我们发现，与接受ICI治疗的非HCC癌症患者和接受索拉非尼治疗的HCC患者相比，接受ICI治疗的HCC患者肝损伤风险更高，联合使用伊匹木单抗-纳武单抗治疗的风险最高。
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