Unveiling Drug-Induced Autoimmune-Like Hepatitis in Autoimmune Hepatitis Patients: A Multicenter Retrospective Study

Abstract

Background and Aims Acute or chronic exposure to drugs or herbal and dietary supplements (HDS) can cause drug-induced autoimmune-like hepatitis (DI-ALH), a self-limiting condition resembling autoimmune hepatitis (AIH). We investigated the prevalence of drug exposure among AIH patients at diagnosis to recognise cases of DI-ALH and discern features predicting AIH development.Methods We retrospectively included 705 patients diagnosed with AIH. DI-ALH was defined using published criteria. The clinical, biochemical, serological, and histological data of DI-ALH and AIH were analysed to identify predictors of the evolution of each phenotype.Results Most patients were female (n = 496, 70%), with a median age of 57 years and a median follow-up of 55 months. A 59% (n = 417) reported exposure to drugs or HDS, and 8% (n = 58) fulfilled the criteria for DI-ALH. Statins and HDS were the most common culprits. Patients with DI-ALH more frequently had acute severe or fulminant hepatitis (22% vs. 12%, p = 0.013) and higher transaminase levels (ALT: 966 vs. 591, p = 0.001) at diagnosis. In total, 97% of the patients received immunosuppression. DI-ALH patients had a faster biochemical response than i-AIH patients (4 vs. 5, p = 0.031), while treatment withdrawal was attempted in only 29% (n = 17). Approximately 30% (n = 17) of DI-ALH cases presented a flare during follow-up. Neither clinical, histological, nor serological findings nor RUCAM and RECAM could predict a DI-ALH flare.Conclusions DI-ALH is often under-recognised in clinical practice, leading to unnecessary long-term immunosuppression. A causal relationship between drugs and AIH, along with an attempt to withdraw treatment and long-term follow-up, is essential to prevent overtreatment-associated risks.