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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. (Hepatology 2011;)
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Histological characteristics do not seem to enable distinction between DI-ALH and AIH.
“Histological characteristics do not seem to enable distinction between these entities.”
From Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report (2023) · cites this paper as [16]
Treatment decisions are often based on experience gained from case reports or expert opinion.
“Treatment decisions are often based on experience gained from case reports or expert opinion.”
From Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report (2023) · cites this paper as [16]
DI-ALH mimics the morphological pattern of AIH, including the prominent lympho-plasmocytic infiltrates in portal spaces and interface hepatitis.
“DI-ALH mimics the morphological pattern of AIH, including the prominent lympho-plasmocytic infiltrates in portal spaces and interface hepatitis.”
From Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report (2023) · cites this paper as [16]
The microscopic findings that might help to discriminate between DI-ALH and AIH are largely unknown, except for advanced fibrosis (i.e., cirrhosis), which is observed only in AIH, but not DI-ALH.
“The microscopic findings that might help to discriminate between the two conditions are largely unknown, except for advanced fibrosis (i.e., cirrhosis), which is observed only in AIH, but not DI-ALH.”
From Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report (2023) · cites this paper as [16]
Whilst a greater degree of fibrosis has been reported in AIH, this may be a reflection of disease chronicity rather than reflective of aetiology.
“Whilst a greater degree of fibrosis has been reported in AIH,14,16,48 this may be a reflection of disease chronicity rather than reflective of aetiology.”
From Nomenclature, diagnosis and management of drug-induced autoimmune-like hepatitis (DI-ALH): An expert opinion meeting report (2023) · cites this paper as [16]
Emperipolesis is a histological feature previously considered typical and pathognomonic for AIH.
“- presence of an intact lymphocyte within cytoplasm of a hepatocyte (emperipolesis),”
From Drug-induced liver injury. Part I: Classification, diagnosis and treatment (2025) · cites this paper as [26]
Interface hepatitis, emperipolesis, and hepatocyte rosette formation are also found in 89%, 34% and 40% of DIAIH cases, respectively.
“are also found in 89%, 34% and 40% of DIAIH cases, respectively [25, 26].”
From Drug-induced liver injury. Part I: Classification, diagnosis and treatment (2025) · cites this paper as [26]
Hepatocyte rosette formation is a histological feature previously considered typical and pathognomonic for AIH.
“- hepatocyte rosette formation (a small group of hepatocytes arranged around a small, sometimes centrally visible lumen), are also found in 89%, 34% and 40% of DIAIH cases, respectively [25, 26].”
From Drug-induced liver injury. Part I: Classification, diagnosis and treatment (2025) · cites this paper as [26]
Interface hepatitis is a histological feature previously considered typical and pathognomonic for AIH.
“- lymphocytic/lymphoplasmacytic infiltrates in portal tracts extending into the lobule beyond the limiting plate into the adjacent lobule with damage and progressive loss of hepatocytes at the portal-lobular interface (interface hepatitis),”
From Drug-induced liver injury. Part I: Classification, diagnosis and treatment (2025) · cites this paper as [26]
Clinical diagnoses of AIH and DIAIH are challenging since both conditions have heterogeneous disease manifestations clinically as well as histopathologically.
“Clinical diagnoses of AIH and DIAIH are challenging since both conditions have heterogeneous disease manifestations clinically as well as histopathologically.”
From Drug-induced liver injury. Part I: Classification, diagnosis and treatment (2025) · cites this paper as [26]
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Research works printed but not linked: 15
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Metadata
- Authors
- Suzuki, A., Brunt, E. M., Kleiner, D. E., Miquel, R., Smyrk, T. C., Andrade, R. J., Lucena, I. M., Castiella, A., Lindor, K., & Björnsson, E.
- Venue
- Hepatology
- Published
- 2011-09-02
- Volume
- 54
- Issue
- 3
- Pages
- 931-939
- ISSN
- 0270-9139
- PMC
- PMC3192933
- Cited by
- 310
- References
- 0
- Language
- en
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