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Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations.

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Date
2014-02
Authors
Kleiner, David E
Chalasani, Naga P
Lee, William M
Fontana, Robert J
Bonkovsky, Herbert L
Watkins, Paul B
Hayashi, Paul H
Davern, Timothy J
Navarro, Victor
Reddy, Rajender
Talwalkar, Jayant A
Stolz, Andrew
Gu, Jiezhun
Barnhart, Huiman
Hoofnagle, Jay H
Drug-Induced Liver Injury Network (DILIN)
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Abstract
Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion. Liver biopsy may contribute to diagnostic accuracy, but the histological features of DILI and their relationship to biochemical parameters and outcomes are not well defined. We have classified the pathological pattern of liver injury and systematically evaluated histological changes in liver biopsies obtained from 249 patients with suspected DILI enrolled in the prospective, observational study conducted by the Drug Induced Liver Injury Network. Histological features were analyzed for their frequency within different clinical phenotypes of liver injury and to identify associations between clinical and laboratory findings and histological features. The most common histological patterns were acute (21%) and chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and cholestatic hepatitis (29%). Liver histology from 128 patients presenting with hepatocellular injury had more severe inflammation, necrosis, and apoptosis and more frequently demonstrated lobular disarray, rosette formation, and hemorrhage than those with cholestasis. Conversely, histology of the 73 patients with cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or fatal hepatic injury in 46 patients was associated with higher degrees of necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among other findings, whereas eosinophils and granulomas were found more often in those with milder injury.We describe an approach for evaluating liver histology in DILI and demonstrate numerous associations between pathological findings and clinical presentations that may serve as a foundation for future studies correlating DILI pathology with its causality and outcome.
Type
Journal article
Subject
Drug-Induced Liver Injury Network (DILIN)
Liver
Humans
Cholestasis
Hepatitis
Acute Disease
Chronic Disease
Necrosis
Biopsy
Prospective Studies
Apoptosis
Phenotype
Adolescent
Adult
Aged
Aged, 80 and over
Middle Aged
Child
Female
Male
Young Adult
Chemical and Drug Induced Liver Injury
Permalink
https://hdl.handle.net/10161/21124
Published Version (Please cite this version)
10.1002/hep.26709
Publication Info
Kleiner, David E; Chalasani, Naga P; Lee, William M; Fontana, Robert J; Bonkovsky, Herbert L; Watkins, Paul B; ... Drug-Induced Liver Injury Network (DILIN) (2014). Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology (Baltimore, Md.), 59(2). pp. 661-670. 10.1002/hep.26709. Retrieved from https://hdl.handle.net/10161/21124.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Barnhart

Huiman Xie Barnhart

Professor of Biostatistics & Bioinformatics
My research interests include both statistical methodology and disease-specific clinical research biostatistics. My statistical research areas include methods for assessing reliability/agreement between methods or raters, evaluating performance of new medical diagnostic tests, missing data, correlated categorical data and methods for clinical trials. My collaborative research include the following clinical areas: cardiovascular imaging, radiology imaging, cardiovascular disease, renal disea
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