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

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)

2020-07-01T15:37:05Z

2020-07-01T15:37:05Z

2014-02

2020-07-01T15:37:03Z

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.

0270-9139

1527-3350

https://hdl.handle.net/10161/21124

eng

Wiley

Hepatology (Baltimore, Md.)

10.1002/hep.26709

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

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

Journal article

Barnhart, Huiman|0000-0003-0988-3439

661

670

2

School of Medicine

Duke Clinical Research Institute

Biostatistics & Bioinformatics

Duke

Institutes and Centers

Basic Science Departments

Published

59