FABP4 and MMP9 levels identified as predictive factors for poor prognosis in patients with nonalcoholic fatty liver using data mining approaches and gene expression analysis

Nonalcoholic fatty liver (NAFLD) may progress to nonalcoholic steatohepatitis (NASH) and ultimately to cirrhosis and hepatocellular carcinoma (HCC). Prognostic markers for these conditions are poorly defined. The aim of this study was to identify predictive gene markers for the transition from NAFL to NASH and then to poorer conditions. Gene expression omnibus datasets associated with a prediction analysis algorithm were used to create a matrix composed of control subject (n = 52), healthy obese (n = 51), obese with NAFL (n = 42) and NASH patients (n = 37) and 19,085 genes in order to identify specific genes predictive of the transition from steatosis to NASH and from NASH to cirrhosis and HCC and thus patients at high risk of complications. A validation cohort was used to validate these results. We identified two genes, fatty acid binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9), which respectively allowed distinguishing patients at risk of progression from NAFL to NASH and from NASH to cirrhosis and HCC. Thus, NAFL patients expressing high hepatic levels of FABP4 and NASH patients expressing high hepatic levels of MMP9 are likely to experience disease progression. Therefore, using FABP4 and MMP9 as blood markers could help to predict poor outcomes and/or progression of NAFL during clinical trial follow-up.