Hepatotoxicity of immune checkpoint inhibitors in cancer patients

Purpose: Immunotherapy is being preferred more and more as a treatment option that is increasingly used. Since this new treatment option increases the activation of the immune system against malignancy, some immune side effects and toxicities are also seen. In this study, we aimed to investigate treatment-induced hepatotoxicity in cancer patients treated with immune checkpoint inhibitors. Methods: In the study, the data of 102 patients who had been treated with immunocheckpoint inhibitors in the Oncology Department of Dicle University until November 2021 were analyzed retrospectively. Patients who received treatment for more than one month were included in the study. Demographic characteristics, laboratory and imaging of the patients included in the study were analyzed from the hospital registry system. Results: Of the 102 patients included in the study, 62 (60.8%) were male and 40 (39.2%) were female. 89 (87.3%) patients consisted of patients receiving anti-PD-1 (nivolumab) and 13 (12.7%) patients receiving anti-CTLA (ipilimumab). Liver metastases were detected in 21 (20,5%) of the patients included in the study. The median age of the patients was calculated as 55.5 (min-max value: 19-88) years. The median duration of immunotherapy treatment was 9 months, and the min-max value was 1-72 months. During the follow-up, it was observed that 13 (12.7%) patients developed hepatotoxicity due to immunotherapy. The median value of the time from the start of treatment to the development of hepatitis was 31 days (min-max value: 16-101 days). 11 patients were evaluated as mild (grade 1) and 2 patients as moderate (grade 2) hepatitis. All of the patients who developed hepatitis regressed without treatment, and the onset of hepatitis did not cause any clinical problems. Hepatotoxicity was observed in 4 (30.8%) of 13 patients receiving ipilimumab (Anti-CTLA4), while it developed in 9 (10.1%) of 89 patients receiving nivolumab (Anti-PD1). A higher rate of hepatotoxicity was observed in patients receiving ipilimumab(p=0.037). Conclusion: Immune checkpoint inhibitors are generally safe with side-effect profiles compared to conventional chemotherapy. However, although hepatotoxicity due to immunotherapy is not common, it can be a serious problem in some patients. In the treatment follow-up of the patients, especially in the first 1-3 days after the beginning of the treatment. It can be seen between months, and patients should be followed up for its development. It should be kept in mind that hepatotoxicity can be seen at every stage of treatment, even more rarely.