Department of Neurological Surgery and The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
InflamaCORE, LLC, Miami, FL 33156, USA.
Int J Mol Sci. 2020 Nov 13;21(22):8580. doi: 10.3390/ijms21228580.
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.
非酒精性脂肪性肝炎（NASH）是一种日益普遍的非酒精性脂肪性肝病的严重形式。当疾病明显进展时，NASH 的症状才会显现。因此，需要识别 NASH 的生物标志物，以便更早地发现疾病并监测疾病的严重程度。炎症小体已被证明在肝脏疾病中发挥作用。在这里，我们对 NASH 患者和健康对照者的血清进行了生物标志物分析（临界值、阳性和阴性预测值、接受者操作特征（ROC）曲线和似然比）的概念验证研究，涉及凋亡相关斑点样蛋白含有半胱氨酸天冬氨酸蛋白酶募集域（ASC）、白细胞介素（IL）-18、半乳糖凝集素-3（Gal-3）和 C 反应蛋白（CRP）。与对照组相比，NASH 患者的血清中 ASC、IL-18 和 Gal-3 水平升高。ASC 的曲线下面积（AUC）最高（0.7317），准确率为 68%，其次是 IL-18（0.7036），准确率为 66%，Gal-3（0.6891），准确率为 61%。此外，我们使用 ASC、IL-18 和 Gal-3 拟合逐步多元逻辑回归模型，以确定患者患有 NASH 诊断的概率，结果 AUC 为 0.71，准确率为 79%，表明联合这些生物标志物可提高其诊断 NASH 的潜力。这些结果表明，ASC、IL-18 和 Gal-3 是 NASH 的可靠生物标志物，联合分析这些分析物可提高这些蛋白质的生物标志物潜力。
