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The role of microRNAs in phenotipic expression of Non Alcoholic Fatty Liver Disease (NAFLD): since simple steatosis to hepatocellular carcinoma

Grant number: 18/03698-2
Support type:Regular Research Grants
Duration: December 01, 2018 - November 30, 2020
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Claudia Pinto Marques Souza de Oliveira
Grantee:Claudia Pinto Marques Souza de Oliveira
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Non Alcoholic Fatty Liver Disease (NAFLD) is one of the most common causes of liver disease today. It covers a wide spectrum of disease, and may present as simple steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). NAFLD is the most common cause of chronic liver disease in the West and is estimated to affect at least 30% of the US population and about 20% here in Brazil. Metabolic syndrome and its clinical components such as diabetes mellitus and obesity are known risk factors for NAFLD. A subset of patients with NAFLD can develop a more severe form, called non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). The prevalence of CHC related to NASH is increasing worldwide, especially in Western countries where 4-22% of HCC cases are now attributable to it. However, the major molecular mechanisms involved in the pathogenesis of NASH remain unknown and the comprehensive genomic profile of HCC related to NASH has not yet been realized. In addition, there are no efficient biomarkers in predicting progression to steatohepatitis, cirrhosis and hepatocellular carcinoma. There is, therefore, an urgent need to develop methods that can identify non-invasively patients at greater risk. And, since NAFLD has a multifactorial etiology, its evolution is clearly influenced by environmental, genetic and epigenetic factors. The objective of this project is to study the relationship between serum levels of several micro-RNAs, including miR-122, miR-29, miR-33a, miR-21, miR-155 and miR-181 and the phenotypic expression of DHGNA of steatosis to hepatocellular carcinoma, including NASH and cirrhosis. A cross-sectional study will be performed in patients with NAFLD diagnosed by liver biopsy, where clinical, epidemiological, biochemical and mainly histological data (degree of fibrosis, and score to assess necro-inflammatory activity, as well differentiation of tumor in HCC samples) and its correlation with serum levels of micro-RNAs . (AU)