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

• Published in: PloS one Vol. 8; no. 12; p. e81974
• Main Authors: 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, Bell, Lauren N, Barnhart, Huiman, Gu, Jiezhun, Serrano, Jose, Bonkovsky, Herbert L
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.12.2013; Public Library of Science (PLoS)
• Subjects: Acute Disease; Albumin; Analytical chemistry; Bile; Chemical and Drug Induced Liver Injury - blood; Chemical and Drug Induced Liver Injury - diagnosis; Chemical and Drug Induced Liver Injury - immunology; Chemokines; Cohort Studies; Cytokines; Cytokines - blood; Diagnostic systems; Enzyme-Linked Immunosorbent Assay; Growth factors; Helper cells; Humans; Immune response; Immunity; Immunity, Innate; Immunoassay; Injuries; Injury analysis; Innate immunity; Interleukin 17; Interleukin 9; Liver; Liver diseases; Lymphocytes T; Medical prognosis; Models, Immunological; Movie theaters; Multiplexing; Platelet-derived growth factor; Platelet-derived growth factor BB; Predictions; Prognosis; RANTES; Rodents; Serum albumin; Tumor necrosis factor-TNF; North Carolina; California; Indiana; United States > US; Indianapolis Indiana
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0081974

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.