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 Saha, Lauren N. Bell, Huiman Barnhart, Jiezhun Gu, Jose Serrano, Herbert L. Bonkovsky

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48 Scopus citations

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

ASJC Scopus subject areas

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

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    Steuerwald, N. M., Foureau, D. M., Norton, H. J., Zhou, J., Parsons, J. C., Chalasani, N., Fontana, R. J., Watkins, P. B., Lee, W. M., Reddy, K. R., Stolz, A., Talwalkar, J., Davern, T., Saha, D., Bell, L. N., Barnhart, H., Gu, J., Serrano, J., & 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