Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance.
Abstract
Drug-induced liver injury (DILI) is the most common cause of acute liver failure in
the United-States. The aim of the study was to describe serum immune profiles associated
with acute DILI, to investigate whether there are profiles associated with clinical
features or types of DILI and/or with prognosis, and to assess temporal changes in
levels. Twenty-seven immune analytes were measured in the sera of 78 DILI subjects
in the Drug-Induced Liver Injury Network (DILIN) and compared with 40 healthy controls.
Immune analytes (14 cytokines, 7 chemokines and 6 growth factors) were measured by
BioPlex multiplex ELISA at DILI onset and after 6 months. A modeling process utilizing
immune principles was used to select a final set of variables among 27 immune analytes
and several additional clinical lab values for prediction of early death (within 6
months of DILI onset). Nineteen of the 27 immune analytes were differentially expressed
among healthy control, DILI onset and 6-month cohorts. Disparate patterns of immune
responses, especially innate and adaptive cellular (mostly TH17) immunity were evident.
Low values of four immune analytes (IL-9, IL-17, PDGF-bb and RANTES) and serum albumin
are predictive of early death [PPV = 88% (95% CI, 65%-100%), NPV = 97% (95% CI, 93%-100%),
accuracy = 96% (95% CI, 92%-100%)].Acute DILI is associated with robust and varying
immune responses. High levels of expression of cytokines associated with innate immunity
are associated with a poor prognosis, whereas high levels of expression of adaptive
cytokines are associated with good long-term prognosis and eventual recovery. Serum
immune analyte profiles at DILI onset appear to be of prognostic, and perhaps, diagnostic
significance.
Type
Journal articleSubject
HumansAcute Disease
Cytokines
Enzyme-Linked Immunosorbent Assay
Prognosis
Cohort Studies
Models, Immunological
Immunity, Innate
Chemical and Drug Induced Liver Injury
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https://hdl.handle.net/10161/21125Published Version (Please cite this version)
10.1371/journal.pone.0081974Publication Info
Steuerwald, Nury M; Foureau, David M; Norton, H James; Zhou, Jie; Parsons, Judith
C; Chalasani, Naga; ... Bonkovsky, Herbert L (2013). Profiles of serum cytokines in acute drug-induced liver injury and their prognostic
significance. PloS one, 8(12). pp. e81974. 10.1371/journal.pone.0081974. Retrieved from https://hdl.handle.net/10161/21125.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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