Cytokine profiles in acute liver injury-Results from the US Drug-Induced Liver Injury Network (DILIN) and the Acute Liver Failure Study Group.

Abstract

Changes in levels of cytokines and chemokines have been proposed as possible biomarkers of tissue injury, including liver injury due to drugs. Recently, in acute drug-induced liver injury (DILI), we showed that 19 of 27 immune analytes were differentially expressed and that disparate patterns of immune responses were evident. Lower values of serum albumin (< 2.8 g/dL) and lower levels of only four analytes, namely, IL-9, IL-17, PDGF-bb, and RANTES, were highly predictive of early death [accuracy = 96%]. The goals of this study were to assess levels of the same 27 immune analytes in larger numbers of subjects to learn whether the earlier findings would be confirmed in new and larger cohorts of subjects, compared with a new cohort of healthy controls. We studied 127 subjects with acute DILI enrolled into the US DILIN. We also studied 118 subjects with severe acute liver injury of diverse etiologies, enrolled into the ALF SG registry of subjects. Controls comprised 63 de-identified subjects with no history of liver disease and normal liver tests. Analytes associated with poor outcomes [death before 6 months, n = 32 of the total of 232 non-acetaminophen (Apap) subjects], were lower serum albumin [2.6 vs 3.0 g/dL] and RANTES [6,458 vs 8,999 pg/mL] but higher levels of IL-6 [41 vs 18], IL-8 [78 vs 48], and MELD scores [30 vs 24]. Similar patterns were observed for outcome of death/liver transplant within 6 months. A model that included only serum albumin < 2.8 g/dL and RANTES below its median value of 11,349 had 83% (or 81%) accuracy for predicting early death (or early death/liver transplant) in 127 subjects from DILIN. No patterns of serum immune analytes were reflective of the etiologies of acute liver failure, but there were cytokine patterns that predicted prognosis in both acute DILI and ALF.

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10.1371/journal.pone.0206389

Publication Info

Bonkovsky, Herbert L, Huiman X Barnhart, David M Foureau, Nury Steuerwald, William M Lee, Jiezhun Gu, Robert J Fontana, Paul J Hayashi, et al. (2018). Cytokine profiles in acute liver injury-Results from the US Drug-Induced Liver Injury Network (DILIN) and the Acute Liver Failure Study Group. PloS one, 13(10). p. e0206389. 10.1371/journal.pone.0206389 Retrieved from https://hdl.handle.net/10161/21123.

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Scholars@Duke

Barnhart

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 outcomes, endpoints, estimands, assessing reliability/agreement between methods or raters, evaluating performance of new medical diagnostic tests, and methods for design of clinical trials. My collaborative research include the following clinical areas: liver injury, cardiovascular imaging, radiology imaging, cardiovascular disease, renal disease, reproductive medicine, Parkinson disease, and aging.


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