Mo1197 Mitochondrial Respiratory Chain Complex Disorders Associated With NAFLD in Childhood Cancer Survivors

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS) and is characterized by increased hepatocyte triglyceride content in the form of lipid droplets. Recent evidence suggests that lysosomal acid lipase (LAL) may play a role in lipid droplet degradation through the autophagic pathway which contributes to the development of insulin resistance. The aim of this study was to investigate the association between LAL activity in the blood and the severity of hepatic steatosis and features of MetS. Methods: Consecutive children with evidence of hepatic steatosis on ultrasound (US) were included. The severity of steatosis was graded as follows: 1 (mild), 2 (moderate), 3 (severe). Demographic, anthropometric, and routine laboratory data were collected on all subjects. Insulin resistance was evaluated by homeostatic model assessment (HOMA-IR). LAL activity was measured in dried blood spot using Lalistat 2 per standard protocol. Spearman rank correlation coefficient (rho) was used to assess the relationship between LAL activity and clinical features. Results: 161 children were included, 56% male, mean age of 12.3 ± 8.6 years, 90% were overweight or obese. Liver US showed mild steatosis in 36%, moderate in 47% and severe in 17%. The mean LAL activity was 1.29 ± 0.66. There was a weak but significant negative correlation between LAL activity and BMI z score (rho = -0.36), fasting insulin (-0.20), HOMA-IR (-0.22) and uric acid (-0.26); p value 90% and severe steatosis (grade 3) on liver US (p < 0.05 for all). Conclusion: Peripheral blood LAL activity correlates with features of the MetS and the severity of hepatic steatosis in children.