CONICET | Buscador de Institutos y Recursos Humanos

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease which prevalence has been constantly increasing linked to the obesity global epidemic. NAFLD histologic spectrum ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellularcarcinoma. Liver biopsy is the only reliable way to diagnose and stage NASH but its invasive nature limits its use. Therefore, the prediction of hepatic injury by means of the development of new noninvasive tests represents a growing medical need. Our aim was to evaluate matrix deposition [hyaluronic acid (HA) and tissue inhibitor of matrix metalloprotein inhibitor-1 (TIMP-1)] and cell-death markers [cytokeratin-18 (M65) and caspase-cleaved cytokeratin-18 (M30)], which correlate with liver injury in a NAFLD patients cohort.Liver biopsies and serum from 34 NAFLD adult patients were analyzed. Histological parameters were evaluated. HA, TIMP-1, M65 and M30 were measured in serum samples.HA showed association with fibrosis severity (p=0.03) and M30 with steatosis (p=0.013), inflammation (p=0.004) and fibrosis severity (p=0.04). In contrast, TIMP-1 and M65 showed no association with any histological parameter of liver injury. The diagnostic accuracy evaluation demonstrated a good performance as less invasive markers of significant fibrosis of both HA (AUROC 0.928) and M30 (AUROC 0.848). In conclusion, biomarkers are essential tools that may provide a quick and accurate diagnosis to patients with life-threatening NAFLD and NASH. HA and M30, together or sequentially determined, demonstrated to be straightforward tests that may be enough to predict significant fibrosis even in a primary care centre of an underdeveloped country