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Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations.
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 articleSubject
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
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https://hdl.handle.net/10161/21124Published Version (Please cite this version)
10.1002/hep.26709Publication 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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Show full item recordScholars@Duke
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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