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

Int J Mol Sci. 2020 Nov 13;21(22):8580. doi: 10.3390/ijms21228580.

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.

Keywords: ASC; NASH; biomarkers; inflammasome; inflammation.

MeSH terms

  • 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

Substances

  • Biomarkers
  • Blood Proteins
  • CARD Signaling Adaptor Proteins
  • Galectins
  • IL18 protein, human
  • Interleukin-18
  • LGALS3 protein, human
  • PYCARD protein, human