Abstract
Non-alcoholic fatty liver disease (NAFLD) contributes essentially to the burden of obesity and can start in childhood. NAFLD can progress to cirrhosis and hepatocellular carcinoma. The early phase of NAFLD is crucial because during this time the disease is fully reversible. Pediatric NAFLD shows unique features of histology and pathophysiology compared to adults. Changes in serum iron parameters are common in adult NAFLD and have been termed dysmetabolic iron overload syndrome characterized by increased serum ferritin levels and normal transferrin saturation; however, the associations of serum ferritin, inflammation, and liver fat content have been incompletely investigated in children. As magnetic resonance imaging (MRI) is an excellent measure for the degree of liver steatosis, we applied this method herein to clarify the interaction between ferritin and fatty liver in male adolescents. For this study, one hundred fifty male pediatric patients with obesity and who are overweight were included. We studied a subgroup of male patients with (n = 44) and without (n = 18) NAFLD in whom we determined liver fat content, visceral adipose tissue, and subcutaneous adipose tissue extent with a 1.5T MRI (Philips NL). All patients underwent a standardized oral glucose tolerance test. We measured uric acid, triglycerides, HDL-, LDL-, total cholesterol, liver transaminases, high sensitive CRP (hsCRP), interleukin-6, HbA1c, and insulin. In univariate analysis, ferritin was associated with MRI liver fat, visceral adipose tissue content, hsCRP, AST, ALT, and GGT, while transferrin and soluble transferrin receptor were not associated with ferritin. Multivariate analysis identified hsCRP and liver fat content as independent predictors of serum ferritin in the pediatric male patients. Our data indicate that serum ferritin in male adolescents with obesity is mainly determined by liver fat content and inflammation but not by body iron status.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and adolescents [1]
Measured by magnetic resonance imaging (MRI), liver fat, and visceral adipose tissue content are significantly elevated in quartile 4
We showed that serum ferritin concentrations in male adolescents are related to hepatic lipid accumulation as verified by MRI and high sensitive CRP (hsCRP) as a marker of concomitant metabolic inflammation
Summary
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and adolescents [1]. Estimations from epidemiological studies suggest that 7–10% of all and up to 30% of children with obesity are affected [2,3,4]. It is dependent on age, ethnicity, and specific genetic determinants and is the highest in children with obesity with up to 38% [5, 6]. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38–61.20), type 2 diabetes (T2D, 22.51%; 95% CI: 17.92–27.89), hyperlipidemia (69.16%; 95% CI: 49.91–83.46%), hypertension (39.34%; 95% CI: 33.15–45.88), and metabolic syndrome (42.54%; 95% CI: 30.06–56.05) [7]. Mechanisms leading to NAFLD include metabolic changes in glucose and lipid homeostasis, disturbed metabolic responses in context of a genetic predisposition, and an excess energy intake [8]
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