Lipofuscinosis as a novel discriminating feature for drug-induced liver injury from autoimmune hepatitis.

Background and objective: Differentiating drug-induced liver injury (DILI) and autoimmune hepatitis (AIH) is a diagnostic challenge. Liver biopsy is recommended in unclear cases, however, clear distinguishing patterns are unknown. We therefore aimed to further identify histopathological features that can discriminate DILI from AIH.

Methods: The clinical and histological data of well-characterised 136 DILI and 43 AIH patients from our prospective cohort on patients with acute liver injury and potential drug-related cause were analysed. Logistic binary regression was performed to identify models that could differentiate both two entities.

Results: Histopathological findings showed high overlaps between DILI and AIH, and overall concordance between histological and clinical diagnosis was low (48.9%). While interface hepatitis, plasma cell infiltration, and portal-intralobular infiltration were favouring AIH, relevant proportions of DILI patients also presented with those features (44.1%, 46.3% and 29.2%, respectively). Interestingly, on multivariate analysis, lipofuscinosis was the only independent predictor of DILI diagnosis, showing a strong association with DILI diagnosis (odds ratio [OR] 10.8; positive predictive value [PPV] 96.2%). Moreover, logistic regression analysis showed that a model combining different histopathological features (lack of interface hepatitis, fibrosis and eosinophils together with presence of cholestasis, steatosis and lipofuscinosis) could differentiate DILI from AIH with an accuracy of 76.5% and a strikingly high sensitivity of 94.9%.

Conclusions: DILI and AIH showed similar histological patterns, however lipofuscinosis was identified as a novel distinctive feature for DILI with an extraordinarily high PPV. Moreover, a model combining a variety of histological features could differentiate both entities with high sensitivity.