Micro RNA Levels in NAFLD

Overview

* Epidemiological study of NAFLD, NASH patients. * Descriptions of altered miRNA profiles in NAFLD patients especially with fibrosis. - Explore the role of circulating miRNAs as biomarkers for the early diagnosis and evaluation of NAFLD patient with fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic steatosis (\>5%-10% of hepatocytes are fatty) in people without history of excessive alcohol consumption (\>21 drinks/week in men and \> 14drinks/week in women) and other disease etiologies that result in fatty liver. The presence of coexisting risk factors such as diabetes, metabolic syndrome, and obesity increases the risk of NAFLD. As a consequence of obesity pandemic and type 2 diabetes, an increased number of patients with NASH-the most severe form of NAFLD-is expected in the near future. According to the latest epidemiological studies, the prevalence of NAFLD is approximately 25% worldwide. In developed countries such as the United States, the prevalence of NAFLD is 30%. In developing countries such as China, the prevalence has reached up to 32.9%. NAFLD comprises a spectrum of pathological conditions, Including simple steatosis (NAFL), nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Studies have shown that approximately one-sixth of NAFL patients progress to NASH, and 20% of NASH patients can develop cirrhosis. The traditional view suggests that HCC formation is a multi-stage process, involving inflammation, fibrosis and cirrhosis. However, recent research found that NASH can progress to HCC without fibrosis and cirrhosis. NAFLD patients are often associated with higher risk of developing both cardiovascular disease and type 2diabetes, therefore early diagnosis of NAFLD and intervention would greatly benefit the patient by preventing the progression of major hepatic and extra hepatic manifestations. In patients with NAFLD, the most important factor is the assessment of fibrosis severity and monitoring fibrosis progression. Most patients remain asymptomatic until their liver functionis compromised. Thus, the identification of the presence and severity of liver fibrosis remains a clinical challenge. Therefore, early predictors need to be investigated. Multiple factors are involved in NAFLD development, including lipotoxicity, insulin resistance, endoplasmic reticulum stress, adipose tissue, gut microbiota, and genetics \[9\]. Our understanding of the pathogenesis of this disease remains limited because of its broad range and complexity. Liver biopsy is the current gold standard in diagnosis and prognosis; nevertheless, it is an expensive and invasive procedure with high sampling error and risk of complications including pain bleeding; and, in very rare cases, death. A biomarker is a patient characteristic assessed as an indicator of a normal or a pathologic process or of a biological response to treatment. Unfortunately, to date, existing non- or minimally invasive biomarkers are inadequate. Circulating extracellular vesicles (exosomes and ectosomes) contain various cellular molecules such as proteins, mRNA, miRNAs, and DNA can serve as biomarkers in NAFLD and NASH. MicroRNAs (miRNAs) are short, non-coding single stranded RNAs strand of 20-25 nucleotides. miRNAs play complicated and important roles in regulating the expression of downstream genes . MiRNAs contribute to the pathogenesis of NAFLD/NASH at various levels of disease development and progression and probably are the most extensively studied epigenetic modifications in NAFLD . miR-122 is the most abundant miRNA in human liver, representing more than 70% of the total liver miRNA pool. During hepatocytes maturation, miR-122 stimulates the expression of 24 hepatocytes-specific genes, including hepatocyte nuclear factor 6 (HNF6) \[13\], and in liver regeneration it has been reported to regulate hepatocytes proliferation and differentiation, recapitulating the developmental processes.

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Central Contacts