The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis vs. drug-induced liver injury

• Published in: Hepatology (Baltimore, Md.) Vol. 54; no. 3; pp. 931 - 939
• Main Authors: Suzuki, Ayako, Brunt, Elizabeth M., Kleiner, David E., Miquel, Rosa, Smyrk, Thomas C., Andrade, Raul J., Lucena, Ma Isabel, Castiella, Agustin, Lindor, Keith, Björnsson, Einar
• Format: Journal Article
• Language: English
• Published: 08-08-2011
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.24481

Distinguishing drug-induced liver injury (DILI) from idiopathic autoimmune hepatitis (AIH) can be challenging. We performed a standardized histologic evaluation to explore potential hallmarks to differentiate AIH vs. DILI. Biopsies from patients with clinically well-characterized DILI (n=35, including 19 hepatocellular injury [HC] and 16 cholestatic/mixed injury [CS]) and AIH (n=28) were evaluated for Ishak scores, prominent inflammatory cell types in portal and intra-acinar areas, presence or absence of emperipolesis, rosette formation and cholestasis in a blinded fashion by 4 experienced hepatopathologists. Histologic diagnosis was concordant with clinical diagnosis in 65% of cases; but full agreement on final diagnosis among the 4 pathologists was complete in only 46% of cases. Interface hepatitis, focal necrosis and portal inflammation were present in all the evaluated cases but were more severe in AIH (p<0.05) than DILI (HC). Portal and intra-acinar plasma cells, rosette formation, and emperiopolesis were features that favored AIH (p<0.02). A model combining portal inflammation, portal plasma cells, intra-acinar lymphocytes and eosinophils, rosette formation, and canalicular cholestasis yielded an area under the ROC curve (AUC) of 0.90 in predicting DILI (HC) vs. AIH. All Ishak inflammation scores were more severe in AIH than DILI (CS) (p≤0.05). The 4 AIH-favoring features listed above were consistently more prevalent in AIH while portal neutrophils and intracellular (hepatocellular) cholestasis were more prevalent in DILI (CS) (p<0.02). The combination of portal inflammation, fibrosis, portal neutrophils and plasma cells, and intracellular (hepatocellular) cholestasis yielded an AUC of 0.91 in predicting DILI (CS) vs. AIH.