Liver Injury due to Intravenous Methylprednisolone in the Drug-Induced Liver Injury Network

Abstract

Background and aims: Short courses of intravenous (iv) methylprednisolone (MP) can cause drug induced liver injury (DILI). The aim of this study was to assess the clinical features and HLA associations of MP-related DILI enrolled in the US DILI Network (DILIN). Methods: DILIN cases with MP as a suspected drug were reviewed. DILIN causality scoring was assigned on a 5-point scale (definite, highly likely, probable, possible, unlikely). All cases with MP causality scores of definite, highly likely or probable were analysed. HLA data from direct sequencing were analysed. Results: Eleven cases of definite, highly likely, or probable MP DILI were identified. The median age was 48 years; 73% were female; median latency to onset was 30 days; 55% were jaundiced; and all had hepatocellular injury with one patient requiring transplantation. Nine of the 11 cases were in patients with multiple sclerosis (MS). Liver biopsies in 7 cases revealed mild acute hepatitis with/without cholestasis. HLA data demonstrated that HLA-DRB115:01, the primary HLA class II allele associated with MS was over-represented. HLA-DQB106:02-HLA-DQA101:02 which is haplotypic with the HLA-DRB115 haplotype was more common in the MP DILI cases compared to other DILI controls (p = 0.03) and to DILI controls exposed to MP (p = 0.04). Conclusion: MP DILI is characterised by hepatocellular injury, short latency and generally rapid recovery. There was no independent HLA haplotype associated with MP DILI.