Differential Analysis of Clinical Characteristics of Liver Injury in Patients with Primary Liver Cancer and Non-Hepatic Malignancies Using PD-1/PD-L1

From November 10th to 14th, 2023, the American Association for the Study of Liver Diseases (AASLD 2023) was grandly held in Boston, USA. A recent research achievement in the field of hepatotoxicity by Dr. Xinyan Zhao's team from Beijing Friendship Hospital affiliated with Capital Medical University was included in the conference proceedings [1]. Hepatology Digest hereby invites the team to elaborate on their research findings, and the relevant content is shared below.

Authors:

- Wang Yan1, Liu Liwei2, Zhao Mengyu1

- Corresponding Author: Xinyan Zhao

- Affiliations:

  1. Liver Disease Center, Beijing Friendship Hospital, Capital Medical University

  2. Department of Liver Diseases, Beijing Youan Hospital, Capital Medical University

  3. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University

In recent years, immune checkpoint inhibitors have been widely used in the treatment of primary liver cancer and other non-hepatic malignant tumors. It is well known that primary liver cancer often occurs in patients with underlying liver diseases such as chronic hepatitis and cirrhosis. Whether the risk and manifestations of liver injury during the use of immune checkpoint inhibitors in these patients differ from those without underlying liver diseases and having other malignancies remains inconclusive. This study aims to explore this issue through a retrospective analysis.

Research Methods

The retrospective study included malignant tumor patients treated with PD-1/PD-L1 inhibitors at Beijing Friendship Hospital affiliated with Capital Medical University from 2015 to 2022. Patient demographic data, laboratory test results, and prognosis data were retrospectively collected. Patients were categorized into groups based on tumor type (primary liver cancer vs. other malignant tumors) and the presence and cause of liver injury during the use of PD-1/PD-L1 inhibitors (no liver injury, immune-mediated liver injury, other causes of liver injury). The clinical differences among these groups were compared.

Research Results

A total of 1335 cases of malignant tumor patients receiving PD-1/PD-L1 inhibitor treatment were included in the study, including 87 cases of primary liver cancer and 1248 cases of other non-hepatic malignant tumors (502 gastrointestinal tumors, 348 urological tumors, 272 other malignant tumors, see Figure 2). The number of treatment cycles in the primary liver cancer group was significantly lower than that in the other non-hepatic malignant tumor group [2 (1-5) vs. 3 (2-6) cycles, P=0.025]. Biochemical indicators (ALT, AST, ALP, GGT, TBIL) in the primary liver cancer group were significantly higher than those in the other malignant tumor group.

The incidence of all-cause liver injury in the primary liver cancer group was significantly higher than that in the non-hepatic malignant tumor group [29 (33.0%) vs. 288 (23.1%), P=0.037]. However, the rate of immune-mediated liver injury in the primary liver cancer group was not significantly higher than that in the non-hepatic malignant tumor group [4 (4.6%) vs. 62 (5.0%), P=0.878]. The increased incidence of all-cause liver injury in the primary liver cancer group was more related to tumor progression rather than immune-mediated liver injury (see Figure 3).

Research Conclusion

In conclusion, this study suggests that the incidence of all-cause liver injury in patients with primary liver cancer during the use of immune checkpoint inhibitors is higher than that in patients with other non-hepatic malignant tumors. However, there is no significant difference in the rate of immune-mediated liver injury between the primary liver cancer group and the other malignant tumor group. The increased incidence of liver injury is more associated with liver cancer progression than immune-mediated liver injury.

Reference:

[1] Wang Y, Liu L, Zhao M, et al. A comparative analysis of liver injury induced by programmed cell death protein-1 inhibitors in patients with hepatocellular carcinoma and other malignant tumors. AASLD 2023. Poster 1705-A.