Abstract
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of diseases from simple steatosis to non-alcoholic steatohepatitis, with approximately 20% risk of progressing to fibrosis and cirrhosis. The aim of this study was to compare the relative expression levels of circulating miR-21, miR-34a, miR-122, miR-125b and miR-375 between healthy controls and NAFLD patients, and to assess the feasibility of microRNAs as potential biomarkers for NAFLD. A cross-sectional study was conducted to evaluate circulating serum miRNAs as potential diagnostic markers for NAFLD. Twenty-eight clinically diagnosed and histologically-confirmed NAFLD patients, as well as 36 healthy controls were enrolled in this study. The relative expression of serum microRNAs were calculated using the comparative cycle threshold with spiked-in C. elegans miR-39 as exogenous internal control. Serum levels of miR-34a and miR-122 were significantly higher in NAFLD patients than in healthy controls (P = <0.0001). Positive correlations were observed between serum miR-34a with very low density lipoprotein cholesterol (VLDL-C) and triglyceride levels. However, the expression levels of miR-34a and miR-122 did not correlate with the histological features of NAFLD. Interestingly, receiver operating characteristic (ROC) curve analysis revealed that miR-34a and miR-122 are potential markers for discriminating NAFLD patients from healthy controls with an area under the curve (AUC) values of 0.781 and 0.858, respectively. Serum levels of miR-34a and miR-122 were found to be significantly higher among NAFLD patients, and were positively correlated with VLDL-C and triglyceride levels. Thus, circulating miR-34a and miR-122 can be used as potential biomarkers for discriminating NAFLD patients from healthy controls. Larger cohorts are required to validate the utility of miR-34a and miR-122 in monitoring liver injury.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation, as well as hepatic cellular degeneration without a history of excessive alcohol intake, and in the absence of other known liver diseases such as chronic hepatitis B (CHB) and chronic hepatitis C (CHC) virus infection
The serum fasting blood sugar (FBS), triglyceride, high density lipoprotein cholesterol (HDL-C), very low density lipoprotein cholesterol (VLDL-C), aspartate transaminase (AST) and alanine transaminase (ALT) levels were found to be significantly different between heathy controls and NAFLD patients (P =
The serum levels of miR-34a and miR-122 were significantly different between healthy controls and NAFLD patients (Fig 1)
Summary
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation, as well as hepatic cellular degeneration without a history of excessive alcohol intake, and in the absence of other known liver diseases such as chronic hepatitis B (CHB) and chronic hepatitis C (CHC) virus infection. NAFLD can be categorized into 2 phenotypes: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatits (NASH). NAFL is defined as the presence of liver steatosis without evidence of hepatic damage which is usually non-progressive, while NASH is often progressive and can lead to cirrhosis and hepatocellular carcinoma [1,2]. In Europe, the prevalence of NAFLD varied from 2% to 44% [4]. It has been reported that Hispanics bear the highest propensity to develop NAFLD with a prevalence of 45% [5]. It is estimated that 30% to 40% of patients with NASH may develop liver fibrosis; about 15% to 20% may develop cirrhosis and 2% to 3% may develop hepatocellular carcinoma. Children with NAFLD may later on develop end-stage liver disease and possibly need transplantation [3]
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