Association between plasminogen activator inhibitor-1 and severity of liver injury and cardiovascular risk in children with non-alcoholic fatty liver disease

Pediatr Obes. 2018 Jan;13(1):23-29. doi: 10.1111/ijpo.12183. Epub 2016 Oct 20.

Abstract

Background: Plasminogen 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.

Objectives: The 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.

Methods: In 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.

Results: We 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.

Conclusions: PAI-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.

Keywords: Children; NAFLD; PAI-1; lipids.

MeSH terms

  • Biomarkers / blood
  • Biopsy
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / pathology*
  • Child
  • Female
  • Humans
  • Inflammation / pathology
  • Insulin Resistance / physiology
  • Lipids / blood*
  • Liver / pathology*
  • Liver Cirrhosis / pathology
  • Male
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Obesity / complications
  • Plasminogen Activator Inhibitor 1 / blood*
  • Retrospective Studies
  • Risk Factors

Substances

  • Biomarkers
  • Lipids
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human