Association Between Plasminogen Activator Inhibitor-1 And Severity Of Liver Injury And Cardiovascular Risk In Children With Non-Alcoholic Fatty Liver Disease

BackgroundPlasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of the endogenous fibrinolytic system and is known to be increased in obesity, insulin resistance and non-alcoholic fatty liver disease (NAFLD). We previously demonstrated that PAI-1 levels were closely related to the amount of hepatic steatosis in children.ObjectivesThe aim of this study was to characterize plasma PAI-1 in relationship to severity of inflammation and fibrosis, as well as to plasma lipids in children with NAFLD.MethodsIn 44 children with NAFLD, plasma PAI-1 levels and lipids were measured at the time of a liver biopsy. Hepatic histological features were systematically scored. Trend analysis was applied to determine the correlation of plasma PAI-1 levels with lipid markers for cardiovascular disease and with the staging of histological features in the liver.ResultsWe found that plasma PAI-1 levels were significantly increased in children with increased severity of steatosis, lobular inflammation, ballooning and fibrosis. Furthermore, PAI-1 was strongly correlated with plasma lipids and insulin resistance indices.ConclusionsPAI-1 appears to be tightly related to both histologic severity of NAFLD as well as systemic features of the disease including insulin resistance and dyslipidemia. PAI-1 may be a mediator of disease progression and future cardiovascular complications in children with NAFLD.