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ASC, IL-18 and Galectin-3 as Biomarkers of Non-Alcoholic Steatohepatitis: A Proof of Concept Study.

Abstract
Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease that is growing in prevalence. Symptoms of NASH become apparent when the disease has progressed significantly. Thus, there is a need to identify biomarkers of NASH in order to detect the disease earlier and to monitor disease severity. The inflammasome has been shown to play a role in liver diseases. Here, we performed a proof of concept study of biomarker analyses (cut-off points, positive and negative predictive values, receiver operating characteristic (ROC) curves, and likelihood ratios) on the serum of patients with NASH and healthy controls on apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18, Galectin-3 (Gal-3), and C-reactive protein (CRP). ASC, IL-18, and Gal-3 were elevated in the serum of NASH patients when compared to controls. The area under the curve (AUC) for ASC was the highest (0.7317) with an accuracy of 68%, followed by IL-18 (0.7036) with an accuracy of 66% and Gal-3 (0.6891) with an accuracy of 61%. Moreover, we then fit a stepwise multivariate logistic regression model using ASC, IL-18, and Gal-3 to determine the probability of patients having a NASH diagnosis, which resulted in an AUC of 0.71 and an accuracy of 79%, indicating that combining these biomarkers increases their diagnostic potential for NASH. These results indicate that ASC, IL-18, and Gal-3 are reliable biomarkers of NASH and that combining these analytes increases the biomarker potential of these proteins.
AuthorsBrianna Cyr, Robert W Keane, Juan Pablo de Rivero Vaccari
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 22 (Nov 13 2020) ISSN: 1422-0067 [Electronic] Switzerland
PMID33203036 (Publication Type: Journal Article)
Chemical References
  • Biomarkers
  • Blood Proteins
  • CARD Signaling Adaptor Proteins
  • Galectins
  • IL18 protein, human
  • Interleukin-18
  • LGALS3 protein, human
  • PYCARD protein, human
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers (blood)
  • Blood Proteins
  • CARD Signaling Adaptor Proteins (blood)
  • Female
  • Galectins (blood)
  • Humans
  • Interleukin-18 (blood)
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease (blood)
  • Proof of Concept Study
  • Prospective Studies

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