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

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.