Diagnosis and management of immune mediated liver injury from checkpoint inhibitors

The aim is to summarize the latest data on the incidence, clinical manifestations, and management of immune- mediated liver injury from checkpoint inhibitors (ILICI).

ILICI develops in 10-15% of oncology patients receiving immunotherapy with most having asymptomatic serum aminotransferase and/or alkaline phosphatase elevations. Most grade 1-2 ILICI patients improve with drug discontinuation and/or short-term oral corticosteroids. In contrast, the 2-3% with grade 3/4 hepatotoxicity frequently require oral or intravenous corticosteroids and some are hospitalized to initiate further immunosuppression with mycophenolate mofetil or azathioprine. Liver biopsy is generally reserved for patients with atypical features or those with severe hepatotoxicity who fail to respond to treatment. Up to 3% of ILICI patients with a cholestatic profile have MRI evidence of intra or extrahepatic cholangitis that responds poorly to immunosuppression. Most ILICI patients improve during follow-up and liver-related death is very uncommon (<1%). Up to 30% of rechallenged ILICI patients develop recurrent hepatotoxicity with a shorter latency.

ILICI is increasingly encountered by gastroenterologists evaluating oncology patients with abnormal liver biochemistries. A stepwise approach to exclude viral hepatitis, alcohol, hepatic metastases, and pancreaticobiliary disease is recommended. The majority of ILICI patients fully recover with ICI discontinuation and short-term corticosteroids or a second line immunosuppressant.