Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance

Nury M. Steuerwald, David M. Foureau, H. James Norton, Jie Zhou, Judith C. Parsons, Naga Chalasani, Robert J. Fontana, Paul B. Watkins, William M. Lee, K. Rajender Reddy, Andrew Stolz, Jayant Talwalkar, Timothy Davern, Dhanonjoy C. Saha, Lauren N. Bell, Huiman Barnhart, Jiezhun Gu, Jose Serrano, Herbert L. Bonkovsky

Research output: Contribution to journalArticle

41 Citations (Scopus)

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%)]. Conclusions: 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.

Original languageEnglish (US)
Article numbere81974
JournalPLoS One
Volume8
Issue number12
DOIs
StatePublished - Dec 27 2013
Externally publishedYes

Fingerprint

Chemical and Drug Induced Liver Injury
blood serum
Liver
cytokines
Cytokines
drugs
liver
Serum
Pharmaceutical Preparations
prognosis
Innate Immunity
antiserum
Immune Sera
interleukin-9
Interleukin-9
death
liver failure
Chemokine CCL5
Acute Liver Failure
Interleukin-17

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Steuerwald, N. M., Foureau, D. M., Norton, H. J., Zhou, J., Parsons, J. C., Chalasani, N., ... Bonkovsky, H. L. (2013). Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance. PLoS One, 8(12), [e81974]. https://doi.org/10.1371/journal.pone.0081974

Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance. / Steuerwald, Nury M.; Foureau, David M.; Norton, H. James; Zhou, Jie; Parsons, Judith C.; Chalasani, Naga; Fontana, Robert J.; Watkins, Paul B.; Lee, William M.; Reddy, K. Rajender; Stolz, Andrew; Talwalkar, Jayant; Davern, Timothy; Saha, Dhanonjoy C.; Bell, Lauren N.; Barnhart, Huiman; Gu, Jiezhun; Serrano, Jose; Bonkovsky, Herbert L.

In: PLoS One, Vol. 8, No. 12, e81974, 27.12.2013.

Research output: Contribution to journalArticle

Steuerwald, NM, Foureau, DM, Norton, HJ, Zhou, J, Parsons, JC, Chalasani, N, Fontana, RJ, Watkins, PB, Lee, WM, Reddy, KR, Stolz, A, Talwalkar, J, Davern, T, Saha, DC, Bell, LN, Barnhart, H, Gu, J, Serrano, J & Bonkovsky, HL 2013, 'Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance', PLoS One, vol. 8, no. 12, e81974. https://doi.org/10.1371/journal.pone.0081974
Steuerwald NM, Foureau DM, Norton HJ, Zhou J, Parsons JC, Chalasani N et al. Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance. PLoS One. 2013 Dec 27;8(12). e81974. https://doi.org/10.1371/journal.pone.0081974
Steuerwald, Nury M. ; Foureau, David M. ; Norton, H. James ; Zhou, Jie ; Parsons, Judith C. ; Chalasani, Naga ; Fontana, Robert J. ; Watkins, Paul B. ; Lee, William M. ; Reddy, K. Rajender ; Stolz, Andrew ; Talwalkar, Jayant ; Davern, Timothy ; Saha, Dhanonjoy C. ; Bell, Lauren N. ; Barnhart, Huiman ; Gu, Jiezhun ; Serrano, Jose ; Bonkovsky, Herbert L. / Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance. In: PLoS One. 2013 ; Vol. 8, No. 12.
@article{a7ef24872ae047bc80c5e1de95960443,
title = "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{\%})]. Conclusions: 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.",
author = "Steuerwald, {Nury M.} and Foureau, {David M.} and Norton, {H. James} and Jie Zhou and Parsons, {Judith C.} and Naga Chalasani and Fontana, {Robert J.} and Watkins, {Paul B.} and Lee, {William M.} and Reddy, {K. Rajender} and Andrew Stolz and Jayant Talwalkar and Timothy Davern and Saha, {Dhanonjoy C.} and Bell, {Lauren N.} and Huiman Barnhart and Jiezhun Gu and Jose Serrano and Bonkovsky, {Herbert L.}",
year = "2013",
month = "12",
day = "27",
doi = "10.1371/journal.pone.0081974",
language = "English (US)",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance

AU - Steuerwald, Nury M.

AU - Foureau, David M.

AU - Norton, H. James

AU - Zhou, Jie

AU - Parsons, Judith C.

AU - Chalasani, Naga

AU - Fontana, Robert J.

AU - Watkins, Paul B.

AU - Lee, William M.

AU - Reddy, K. Rajender

AU - Stolz, Andrew

AU - Talwalkar, Jayant

AU - Davern, Timothy

AU - Saha, Dhanonjoy C.

AU - Bell, Lauren N.

AU - Barnhart, Huiman

AU - Gu, Jiezhun

AU - Serrano, Jose

AU - Bonkovsky, Herbert L.

PY - 2013/12/27

Y1 - 2013/12/27

N2 - 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%)]. Conclusions: 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.

AB - 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%)]. Conclusions: 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.

UR - http://www.scopus.com/inward/record.url?scp=84893663493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893663493&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0081974

DO - 10.1371/journal.pone.0081974

M3 - Article

C2 - 24386086

AN - SCOPUS:84893663493

VL - 8

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e81974

ER -