Autoimmune, Cholestatic and Biliary Disease
Article first published online: 8 AUG 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 54, Issue 3, pages 931–939, 2 September 2011
How to Cite
Suzuki, A., Brunt, E. M., Kleiner, D. E., Miquel, R., Smyrk, T. C., Andrade, R. J., Isabel Lucena, M., Castiella, A., Lindor, K. and Björnsson, E. (2011), The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury. Hepatology, 54: 931–939. doi: 10.1002/hep.24481
Potential conflict of interest: Nothing to report.
The Spanish DILI Registry is supported, in part, by research grants from the Agencia Española del Medicamento and Fondo de Investigación Sanitaria (PS 09/01384). This research was also supported, in part, by the Intramural Research Program of the National Iinstitues of Health, National Cancer Institute.
- Issue published online: 25 AUG 2011
- Article first published online: 8 AUG 2011
- Accepted manuscript online: 14 JUN 2011 08:07AM EST
- Manuscript Accepted: 27 MAY 2011
- Manuscript Received: 7 JAN 2011
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 versus 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, the presence or absence of emperipolesis, rosette formation, and cholestasis in a blinded fashion by four experienced hepatopathologists. Histologic diagnosis was concordant with clinical diagnosis in 65% of cases; but agreement on final diagnosis among the four pathologists was complete in only 46% of cases. Interface hepatitis, focal necrosis, and portal inflammation were present in all 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 receiver operating characteristic curve (AUROC) of 0.90 in predicting DILI (HC) versus AIH. All Ishak inflammation scores were more severe in AIH than DILI (CS) (P ≤ 0.05). The four AIH-favoring features listed above were consistently more prevalent in AIH, whereas 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) versus AIH. Conclusion: Although an overlap of histologic findings exists for AIH and DILI, sufficient differences exist so that pathologists can use the pattern of injury to suggest the correct diagnosis. (Hepatology 2011;)