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 druginduced 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

Monocyte-derived hepatocyte-like cells for causality assessment of idiosyncratic drug-induced liver injury

“…These findings are consistent with previous reports showing NSAIDs, anti-infectives and immunomodulatory drugs as frequent causes of iDILI 36–40. Phenprocoumon is an oral anticoagulant used predominantly in Germany, yet also linked to iDILI with a potential autoimmune mechanism 41 42. Metamizole has been rarely linked to liver injury, yet immunological mechanisms are suspected 43…”

Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis

“…DILI cases with negative titres of all four AAB types during the episode were considered to be AAB negative, whereas AAB-positive cases had positive titres of at least one of the AABs during the DILI episode and no further symptoms indicative of AIH. Drug-induced AIH cases (AIH phenotypes induced by drugs, typically minocycline, nitrofurantoin, statins and biologic agents [24]) were excluded from the current study. Fifty cases diagnosed with idiopathic AIH by the authors A.C., P.O.…”

Antituberculosis Drug-Induced Liver Injury with Autoimmune Features: Facing Diagnostic and Treatment Challenges

“…In this particular patient, 2nd DILI occurred later (more than 2 months after initiating this second-line treatment), while completely different and relatively safe-hepatic drugs were used and with autoimmune features. There are at least three clinical scenarios proposed for DILI with autoimmune features (Table 1): AIH with superimposed DILI, drug-induced AIH (DI-AIH), and immune-mediated DILI (IM-DILI) [3]. There is significant overlap of clinical and histological features between them and, in some instances, mixed features of DI-AIH and IM-DILI, as well as DILI with positive autoantibodies [3].…”