Corticosteroid therapy for drug-induced liver injury: Mind the gap!

Idiosyncratic drug-induced liver injury (DILI) resolves following discontinuation of the causative drug in about 80% of individuals. However, liver injury may persist beyond 6 months in 10%-15% of patients, and about 10% die within 2 years of DILI onset. DILI may progress to liver failure even after withdrawal of the offending medication in up to 10% of patients. Consequently, corticosteroids, because of their anti-inflammatory properties, have been used to prevent progression of DILI. With the advent of highly effective checkpoint inhibitors for the treatment of a variety of cancers, corticosteroids are increasingly used at high doses with the intention of accelerating resolution of liver injury. However, there is no evidence that corticosteroids hasten resolution of acute liver injury or reduce the risk of death or liver transplantation in acute DILI. In fact, corticosteroids can impair tissue repair and regeneration and may induce resistance, particularly when used at high doses for prolonged periods to treat checkpoint inhibitor-induced liver injury (ChILI). Indeed, their use has been associated with delayed resolution of ChILI and increased adverse effects. When used to treat immune-related adverse events within 2 months of initiating checkpoint inhibitors across a wide range of cancers, corticosteroids have even been associated with reduced overall survival. Corticosteroid-sparing approaches appear to be safe and effective in the majority of patients with ChILI. A modest dose of prednisolone, tapered over 4 weeks, may be considered selectively in patients with ChILI when bilirubin continues to rise after withdrawal of the checkpoint inhibitor, liver histology demonstrates marked ongoing necroinflammation, and cholestasis or cholangiopathy has been excluded.