Immune-mediated liver injury caused by checkpoint inhibitors: A case series and review of the literature.
Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 agents, exhibit notable efficacy across various types of cancer. Nevertheless, they can trigger immune-related adverse events, among which immune-mediated liver injury (ILICI) occurs in 5-10% of patients. Corticosteroids are currently recommended for management of ILICI; however, the timing, presentation and response to treatment may vary widely. The present study retrospectively reviewed five male patients (median age, 69 years) with various malignancies receiving ICIs who developed ILICI. All patients were treated with anti-PD-1 therapy, and two additionally received anti-CTLA-4 therapy. No patients had a history of liver disease, autoimmune disorders or notable alcohol use, and no relevant drug allergies or toxic exposures were reported. Four patients developed grade 3-4 hepatotoxicity. The median time to onset was 15.5 months (range: 1-30 months), illustrating the delayed and unpredictable nature of ILICI. All patients underwent comprehensive evaluation to exclude other causes of liver injury. In selected cases, liver biopsy revealed features consistent with autoimmune-like hepatitis, aiding in diagnosis and assessment of severity. All patients received systemic glucocorticoids, with resolution of liver injury in most cases. One patient required additional immunosuppressive therapy due to steroid-refractory disease. Notably, liver function tests normalized in three patients following treatment, whereas two patients died from ILICI. The present case series highlights the variable onset and presentation of ILICI, which may occur shortly or long after initiation of ICIs. Timely recognition and prompt treatment are integral components of clinical care. In addition, liver biopsy, while not routinely recommended, can provide valuable diagnostic information in complex cases. The current study provides detailed clinical documentation and biopsy information; however, its interpretation is influenced by the small sample size and retrospective nature of the study. The findings support existing guidelines,and underscore the need for enhanced clinical awareness and standardized management protocols.