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. The injury may persist in 10%-15% beyond 6 months and about 10% die within 2 years from the time of DILI onset. DILI may progress to liver failure even after the withdrawal of the medication in up to 10% of people and therefore treatment with corticosteroids for its anti-inflammatory property has been used to prevent the progression of DILI. With the advent of highly effective checkpoint inhibitors for the treatment of variety of cancers, corticosteroids are used liberally in high doses with an intent to accelerate resolution of liver injury. However, there is no evidence that corticosteroids hasten the resolution of acute liver injury, nor avert death or need of liver transplantation in acute DILI. Corticosteroids can impair repair and regeneration as well as induce resistance especially when used in checkpoint inhibitor-induced liver injury (ChILI) in high doses over longer periods; in fact, treatment has been associated with a delayed resolution of ChILI and increased adverse effects. When used to treat immune-related adverse events within 2 months of initiation of checkpoint inhibitors for wide range of cancers, corticosteroids have even been associated with reduced overall survival. Corticosteroid sparing approaches are safe and effective in majority of patients with ChILI. A modest dose of prednisolone that is tapered off over 4 weeks may selectively be used in ChILI when bilirubin rises progressively after the drug withdrawal, when liver histology demonstrates marked ongoing necroinflammation and once cholestasis or cholangiopathy have been excluded.