Retinol-Binding Protein 4: A Promising Circulating Marker of Liver Damage in Pediatric Nonalcoholic Fatty Liver Disease

Abstract

Noninvasive methods are needed to identify pediatric nonalcoholic fatty liver disease (NAFLD), the most frequent chronic liver disease in children and adolescents in industrialized countries. Retinol-binding protein 4 (RBP4) is an adipocytokine that has been associated with the pathogenesis of insulin resistance. We tested the serum levels of RBP4 to assess their associations with the metabolic profile and histologic features in a large well-characterized group of children with NAFLD. The study included 59 children with biopsy-proven NAFLD. Histologic analyses were performed by an experienced hepatopathologist; the NAFLD activity score and fibrosis score were calculated for each patient. RBP4 levels in serum samples were measured by an enzyme-linked immunosorbent assay analysis. Anthropometric, blood pressure, and metabolic profile analyses (including glucose tolerance, fasting glucose, insulin, and lipid panel tests) were performed on samples from all patients. Decreasing levels of RBP4 were associated significantly with increasing levels of serum triglyceride. High levels of RBP4 were associated significantly with low necroinflammatory activity, a low NAFLD activity score, and a low fibrosis score. Furthermore, serum RBP4 levels decreased significantly as disease severity increased; there was a stepwise decrease in RBP4 from children with steatosis (3.8 mg/dL) to borderline nonalcoholic steatohepatitis (2.9 mg/dL) to definitive nonalcoholic steatohepatitis (1.9 mg/dL) (P < .0001). This association remained significant after adjusting for other relevant clinical variables. Our study shows an inverse relationship between RBP4 levels and degree of liver damage. RBP4 therefore might be a potential novel noninvasive marker of severity of pediatric NAFLD.