Endocrine Abstracts

Metabolic (dysregulation)-associated fatty liver disease (MAFLD) is the main cause of liver dysfunction, showing a prevalence of 20-30% in the general population and 57-74% among patients with obesity. MAFLD comprises a spectrum of chronic liver diseases, ranging from simple hepatic steatosis to non-alcoholic steatohepatitis or NASH, which can lead to advanced fibrosis and cirrhosis, increasing the risk of hepatocellular carcinoma (HCC). HCC is the most frequent, heterogeneous, aggressive and worst-prognosis primary liver subtype, representing 80-90% of all cases and exhibiting a 5-year survival rate of 17%. The development of HCC is a complex process that normally occurs in the context of chronic liver disease and cirrhosis, which has been recently shown to be closely associated with the presence of obesity and MAFLD. This represents a serious threat for global health in that the prevalence of obesity and MAFLD has increased dramatically and can lead to an increment of cases of advanced liver disease, cirrhosis and HCC. Therefore, we are trying to understand the cellular and molecular events associated to the development and progression of chronic liver disease. One of the most drastically altered biological processes during the progression of MAFLD is the processing of RNA and its alternative splicing. For this reason, we are characterizing the landscape of spliceosomal (spliceosome components and splicing factors) changes occurring during the development and progression of chronic liver disease from MAFLD and NASH to HCC, as well as their molecular and clinical implications to identify novel molecular markers for the diagnostic and/or prognostic of the different stages of MAFLD, as well as therapeutic targets in the management of this prevalent pathology.