Pathologic Impact of Insulin Resistance and Sensitivity on the Severity of Liver Histopathology in Pediatric Non-Alcoholic Steatohepatitis

Abstract

Purpose: Insulin resistance (IR) has an important role in the development of non-alcoholic steatohepatitis (NASH). We aimed to analyze the association between liver histopathology and IR in pediatric patients with NASH. Materials and Methods: In 24 children with non-alcoholic fatty liver disease (NAFLD), we investigated whether the hepatic pathologic characteristics have relations with following three biochemical indices; IR index including homeostasis model assessment of IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity indices-free fatty acid (ISI-FFA). Results: Among 24 patients, 16 (66.6%) had a high NAFLD activity score (NAS), which is diagnostic of NASH. Higher serum triglyceride level was significantly correlated with a high NAS. Higher steatosis grades were significantly associated with low insulin sensitivity (p=0.023). In addition, severe lobular inflammation was associated with higher IR: HOMA-IR (p= 0.014) and QUICKI (p= 0.023). Severe fibrosis correlated with low insulin sensitivity and high IR indexes: ISI-FFA (p= 0.049), HOMA-IR (p= 0.028), and QUICKI (p= 0.007). Conclusion: Patients with high IR had more severe lobular inflammation and hepatic fibrosis. Analyses of biochemical and endocrine parameters can be applied to determine the severity of the hepatic pathologic status in patients with NASH, especially in children who cannot undergo a liver biopsy.