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.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease, which ranges from steatosis to non-alcoholic steatohepatitis (NASH), the most severe type [1]
Serum samples from NASH patients and normal age-matched controls were analyzed for the protein levels of a caspase recruitment domain (ASC) (p = 0.0003, Figure 1A), IL-18 (p = 0.0014, Figure 1B), Gal-3 (p = 0.008, Figure 1C), and C-reactive protein (CRP) (p = 0.4385, (Figure 1D)
We provide evidence that ASC, IL-18, and Gal-3 potentially play a role in the pathology of NASH and may serve as reliable biomarkers of NASH
Summary
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease, which ranges from steatosis to non-alcoholic steatohepatitis (NASH), the most severe type [1]. A patient with steatosis may eventually progress to NASH if no treatment is initiated. NASH is characterized by steatosis, inflammation, and a characteristic pattern of hepatocellular injury [1]. NASH may progress to cirrhosis, cancer, and eventually the patient may require a liver transplant [1]. The prevalence of NASH has grown over the last few decades, and it is predicted to increase in frequency. The diagnosis of NASH is made by a liver biopsy. Due to the invasive nature of this diagnostic method and the severity of the disease, it is imperative to develop a less invasive test using blood biomarkers in order to diagnose and monitor the disease with more ease and accuracy
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