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

Ayako Suzuki, Elizabeth M. Brunt, David E. Kleiner, Rosa Miquel, Thomas C. Smyrk, Raul J. Andrade, M. Isabel Lucena, Agustin Castiella, Keith Lindor, Einar Björnsson

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)931-939
Number of pages9
JournalHepatology
Volume54
Issue number3
DOIs
StatePublished - Sep 2 2011
Externally publishedYes

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Chemical and Drug Induced Liver Injury
Autoimmune Hepatitis
Biopsy
Liver
Cholestasis
Rosette Formation
Plasma Cells
Wounds and Injuries
Inflammation
Emperipolesis
Neutrophils
Acinar Cells
Eosinophils
ROC Curve
Hepatitis
Area Under Curve
Fibrosis
Necrosis

ASJC Scopus subject areas

  • Hepatology

Cite this

Suzuki, A., Brunt, E. M., Kleiner, D. E., Miquel, R., Smyrk, T. C., Andrade, R. J., ... Björnsson, E. (2011). The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury. Hepatology, 54(3), 931-939. https://doi.org/10.1002/hep.24481

The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury. / Suzuki, Ayako; Brunt, Elizabeth M.; Kleiner, David E.; Miquel, Rosa; Smyrk, Thomas C.; Andrade, Raul J.; Isabel Lucena, M.; Castiella, Agustin; Lindor, Keith; Björnsson, Einar.

In: Hepatology, Vol. 54, No. 3, 02.09.2011, p. 931-939.

Research output: Contribution to journalArticle

Suzuki, A, Brunt, EM, Kleiner, DE, Miquel, R, Smyrk, TC, Andrade, RJ, Isabel Lucena, M, Castiella, A, Lindor, K & Björnsson, E 2011, 'The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury', Hepatology, vol. 54, no. 3, pp. 931-939. https://doi.org/10.1002/hep.24481
Suzuki, Ayako ; Brunt, Elizabeth M. ; Kleiner, David E. ; Miquel, Rosa ; Smyrk, Thomas C. ; Andrade, Raul J. ; Isabel Lucena, M. ; Castiella, Agustin ; Lindor, Keith ; Björnsson, Einar. / The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury. In: Hepatology. 2011 ; Vol. 54, No. 3. pp. 931-939.
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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.",
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