Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease

Abstract

The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease

Keywords: Drug-induced liver injury, Autoimmune hepatitis, Drugs, Drug-induced autoimmune hepatitis, Drug-induced autoimmune liver disease

Core tip: Drug-induced autoimmune liver disease (DIAILD) is a poorly defined and under-reported liver disorder, and, probably, a underestimated liver disease. A small number of drug-induced liver injury (DILI) cases exhibit features typical of autoimmune hepatitis (AIH). To differentiate between true AIH triggered by drugs (DI-AIH) and immune mediated DILI still remains a challenge. Patients diagnosed with DIAILD have frequently had a previous episode of hepatotoxicity. We consider that some basic requirements are needed to be considered before supporting a drug as a trigger of AIH and they should be taken into account by authors, reviewers and editors when cases are published and made available to the scientific community.