The Role of Genetic Predisposition, Programing During Fetal Life, Family Conditions, and Post-natal Diet in the Development of Pediatric Fatty Liver Disease

Abstract

Objective: To evaluate, in patients with nonalcoholic fatty liver disease (NAFLD), the role of lifetime exposures associated with genetic predisposition, family history (parental obesity, economic income), programming during fetal life (gestational age, birthweight), being breastfed or not, and later biomarkers of dietary habits and lifestyle in the development of fibrosis.

Study design: In total, 182 children with overweight/obesity diagnosed with NAFLD proven by biopsy results were enrolled in our study and evaluated for liver fibrosis. We estimated prevalence ORs of fibrosis according to genetics, parental obesity, occupational socioeconomic status (SES), birth weight, breastfeeding, fructose intake (indicator of junk food consumption), and vitamin D status (inflammatory indicator) using logistic regression models, adjusted for age and children's body mass.

Results: One hundred thirty-seven patients (75.3%) had liver fibrosis, and 45 patients (24.7%) did not have liver fibrosis. The ORs of fibrosis were significant (P < .05) for patatin like phospholipase domain-containing 3-GG genotype (OR 2.1), parental obesity (OR 2.9), not being breastfed (OR 3.1), vitamin D status (<20 mg/dL) (OR 1.24), and fructose consumption (OR 1.6 per 1 g/day increase), whereas a high SES maternal occupation was inversely associated with fibrosis (OR 0.30).

Conclusions: Our results show independent roles of the patatin like phospholipase domain-containing 3 gene, parental obesity, maternal SES, and postnatal diet and lifestyle in the development of progressive liver disease secondary to NAFLD.

Keywords: life course; liver fibrosis; pediatric fatty liver disease.