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

Abstract

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.

Conflict of interest statement

Conflict of interest: Authors do not have conflict of interest.

Copyright © 2011 American Association for the Study of Liver Diseases.

Figures

Figure 1

Drug Induced Liver Injury. (A) A markedly expanded portal tract (upper) with marked, plasma cell rich inflammation and interface activity (white arrows). There are scattered foci of inflammation in the lobules (black arrow), but hepatocyte rosettes are not seen. (B) The portal tract (upper) has mixed chronic inflammation predominated by plasma cells. There is interface activity and foci of spotty necrosis (white arrow) within the lobules adjacent to the portal tract. A single acidophil body (apoptotic body) is also seen near the center lower portion of the field (black arrow). (C) In this field, the hepatocytes are swollen and have densely eosinophilic cytoplasm and marked anisonucleosis. There is lobular disarray and canalicular cholestasis (black arrows). A mild inflammatory infiltrate is seen; it is predominantly characterized by polymorphonuclear leukocytes in small aggregates. Scattered macrovesicular steatosis is noted. (D) The perivenular hepatocytes are swollen and some have reticulated cytoplasm. Some of the hepatocytes are forming rosettes (white arrow). There is hemorrhage around the terminal hepatic venule (black arrows). Numerous pigmented Kupffer cells are noted in the sinusoids, either in groups or as single cells. In addition, inflammatory cells appear to be within the sinusoids, including plasma cells.

Figure 2. Autoimmune hepatitis

(A) Marked interface activity with disruption of the limiting plate (middle, white arrows). Adjacent hepatocytes are swollen, suggesting hepatocyte injury. The interface activity is dominated by plasma cells (black arrows). (B) An expanded portal tract (right) with marked interface activity (white arrows). There is spotty lobular inflammation composed mainly of lymphocytes (black arrow). Prominent plasma cell infiltration is present. (C) Massive portal expansion and severe interface activity with prominent plasma cell infiltration. Scattered eosinophils are also noted (black arrow). (D) Higher magnification shows the involvement of plasma cells in the interface activity. Russell bodies are seen in some plasma cells (black arrow).