Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Pediatrics, Yale University School of Medicine, New Haven, CT.
Department of Pediatrics, University of Campania "L. Vanvitelli", Napoli, Italy.
Seattle Children's Hospital, Seattle, WA.
We conducted a prospective study in a large, multiethnic cohort of obese adolescents to characterize clinical and genetic features associated with pediatric Non-Alcoholic Fatty Liver (NAFL), the most common cause of chronic liver disease in youth.
A total of 503 obese adolescents were enrolled, including 191 (38.0%) Caucasians, 134 (26.6%) African Americans, and 178 (35.4%) Hispanics. Participants underwent abdominal magnetic resonance imaging (MRI) to quantify hepatic fat content, an oral glucose tolerance test to assess glucose tolerance and insulin sensitivity, and the genotyping of three SNPs associated with fatty liver (PNPLA3 rs738409, GCKR rs1260326, and TM6SF2 rs58542926). Assessments were repeated in 133 patients after a 2-year follow-up.
The prevalence of fatty liver was 41.6% (209 patients) and ranged widely among ethnicities, being 42.9% in Caucasians, 15.7% in African Americans, and 59.6% in Hispanics (p<0.0001). Among patients with fatty liver, African Americans showed the highest prevalence of altered glucose homeostasis (66%, p=0.0003). Risk factors for fatty liver incidence were Caucasian or Hispanic ethnicity (p=0.021), high fasting C-peptide levels (p=0.0006) and weight gain (p=0.0006), while baseline HFF% (p=0.004) and weight loss (p=0.032) predicted resolution of NAFL at follow-up. Adding either gene variant to these variables improved significantly the model predictive performance.
African American obese adolescents are relatively protected from liver steatosis but are more susceptible to the deleterious effects of fatty liver on glucose metabolism. The combination of ethnicity/race with markers of insulin resistance and genetic factors might help identify obese youth at risk for developing fatty liver.