Side Effect Management of Immune-related Hepatotoxicity Due to Immune Checkpoint Inhibitors

The mechanism by which immune checkpoint inhibitors (ICI) cause immune-mediated liver injury is unclear. In 2017, the Society for Immunotherapy of Cancer (SITC) published guidelines for managing immunotherapy toxicity. This article aims to compile clinical approaches to cases of hepatotoxicity associated with immunotherapies (ILICI) in a multicenter setting. This will contribute to the literature by providing data from a larger number of patients. This article is important for ILICI clinical management because it enables the continuation of treatment and raises awareness of these immunotherapy side effects. The study included 56 patients from 20 centers. Grade 3-4 hepatic insufficiency occurred in 24 patients (42.9%). Five (8.9%) patients died due to hepatic insufficiency. Liver biopsies of these 5 patients were consistent with ILICI. The median number of treatment cycles before ILICI developed was 5 (minimum: one, maximum: 80). Steroid therapy was administered to all patients except 6. Eighteen patients who were unresponsive to steroids received various second-line treatments. Some patients received various treatments, such as third-, fourth-, and fifth-line treatments, after the second-line treatment. There was no significant correlation between the median number of ICI cycles and serious adverse events (AST, ALT, bilirubin, and hepatic failure) (P=0.186, P=1.000, P=0.599, and P=0.484). In addition, no significant correlation was observed between grade 3-4 adverse events and ICI treatment in the first versus subsequent lines (P>0.05). ILICI is a rare but serious condition, so the treatment modalities used are important. We believe raising awareness of ILICI and evaluating second-line treatments used in steroid-refractory cases contributes to the literature by pooling these treatments together.