Liver biopsy findings and clinical correlates in immune-mediated liver injury from checkpoint inhibitors.

backgroundImmune-mediated liver injury from checkpoint inhibitors develops in up to 10% of treated patients. The aim of this study was to describe the relationship between standard liver histopathological findings and clinical presentation and outcomes in a cohort of 67 adult patients.

methodsLiver biopsies from 67 ICI-treated patients enrolled in the Drug-Induced Liver Injury Network and from the Montpellier, France, registry were scored for 42 features. Exploratory analyses of histological features with clinical presentation and outcomes are provided.

resultsThe median age of patients was 62.5 years, 45% received pembrolizumab, and 24% received ipilimumab-nivolumab. The median latency to liver injury onset was 72 days, and the median time to liver biopsy was 20 days. The 52% with acute hepatocellular injury were significantly younger and had more severe inflammatory scores, granulomas, and necrosis on biopsy than those with mixed- or cholestatic injury, who had more ductular reaction and cholangitis. Patients biopsied on corticosteroids had significantly less severe inflammation, fewer granulomas, and less cholestasis. Mild macrovesicular steatosis was common (65%) and associated with diabetes and patient BMI but not corticosteroid use. Pembrolizumab-treated patients presented later and were more likely to have a cholestatic enzyme pattern and ductular injury on biopsy compared with those with hepatitis from ipilimumab/nivolumab.

conclusionsLiver histology findings were associated with presenting laboratory features in this retrospective, exploratory study of 67 ICI hepatitis patients. Necroinflammatory activity was substantially less in subjects biopsied while on corticosteroids, which may impact clinical management decisions.