The Higher Incidence of Liver Injury in HCC Patients Compared to Other Malignancies During Immune-Checkpoint Inhibitor Therapy is Primarily Due to Tumor Progression

Yan Wang,1,* Liwei Liu,2,* Mengyu Zhao,1,* Wei Chen,3 Yu Chen,2 Xinyan Zhao1 1Liver Research Center, Beijing Friendship Hospital, Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Disease, Capital Medical University, Beijing, People’s Republic of China; 2Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You’an Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Gastroenterology, Beijing Friendship Hospital, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xinyan Zhao, Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory on Translational Medicine on Cirrhosis, National Clinical Research Center for Digestive Disease, 95 Yong-an Road, Xi-Cheng District, Beijing, 100050, People’s Republic of China, Email [email protected] Yu Chen, Fourth Department of Liver Disease (Difficult & Complicated Liver Diseases and Artificial Liver Center), Beijing You’an Hospital, Capital Medical University, No. 8, Xi Tou Tiao, Youanmen Wai, Fengtai District, Beijing, 100069, People’s Republic of China, Email [email protected]: The study explores the incidence and clinical features of immune-related liver injury (irLI) in hepatocellular carcinoma (HCC) patients compared to those with other malignancies receiving immune checkpoint inhibitors (ICIs).Methods: A retrospective analysis was conducted on patients treated with ICIs at Beijing Friendship Hospital. Individuals who experienced liver injury consistent with the criteria specified in the Common Terminology Criteria for Advanced Event version 5.0 for irLI were included in the study. The cohort was divided into an HCC group and a non-HCC malignancy group. HCC patients were further classified into three subgroups based on liver injury: no injury, irLI, or non-immune-related liver injury. Data on demographics, laboratory results, and mortality rates were compared.Results: The study included 292 hCC patients and 1248 patients with other malignancies. Both groups underwent a similar number of ICIs cycles (p=0.237). Liver injury was more common in HCC patients [98 (33.6%) vs 288 (23.1%), p< 0.001], but the irLI incidence was comparable between the groups [17 (5.8%) vs 62 (5.0%), p=0.556]. Tumor progression-related liver injury was higher in HCC patients (12.0%) compared to other malignancies (4.6%). Mortality rates showed no significant differences between groups.Conclusion: HCC patients with underlying liver disease are more prone to liver injury during ICIs therapy, mainly due to tumor progression rather than irLI. Keywords: immune checkpoint inhibitors, hepatocarcinoma, liver injury