ESPE Abstracts (2015) 84 P-2-328

miR-122 and Non-Alcoholic Fatty Liver Disease in Prepubertal Obese Children

Elena Inzaghia, Stephanie Brandtb, Julian Roosb, Stefano Cianfarania,c, Valerio Nobilia, Mauro Colajacomoa, Tadej Battelinod, Kotnik Primozd, Martin Wabitschb & Pamela Fischer-Posovszkyb

aOspedale Pediatrico Bambino Gesù, Rome, Italy; bUniversitätsklinik für Kinder- und Jugendmedizin, Ulm, Germany; cKarolinska Institutet, Stockholm, Sweden; dUniversity Children’s Hospital, Ljubljana, Slovenia.

Background: The incidence of non-alcoholic fatty liver disease (NAFLD) is dramatically increasing among children worldwide. The gold standard for diagnosis is the liver biopsy. Reliable serum markers are lacking. Recently, circulating miRNAs have been studied as biomarkers of disease progression. Specifically, miR-122 was proposed as predictive marker for liver disease in adults, while no data are available for children.

Objective and hypotheses: To investigate the relationship between circulating miR-122 levels and liver steatosis severity and metabolic parameters in obese children.

Method: Antropometry, biochemical and metabolic assessment were performed in 50 prepubertal obese children (15 female, age 9.78±2.17 yrs, BMI SDS 3.44±1.39). Serum cytokeratin-18 (CK18) fragment, a novel biomarker of NAFLD, was determined by ELISA. In 44 subjects liver ultrasound was performed revealing no (n=19, group 0), mild (n=15, group 1), moderate (n=8, group 2), or severe steatosis (n=2, group 3). Serum miR-122 was determined by qPCR.

Results: CK18 did not display a gender dimorphism, while miR-122 was higher in male subjects (1.06±1.55 vs 0.28±0.29, P 0.045). CK18 positively correlated with serum triglycerides (r=0.38, P=0.006), AST (r=0.54, P<0.0001), ALT (r=0.42, P=0.002), and GGT (r=0.26, P=0.07). miR-122 positively correlated with age (r=0.36, P=0.01), CK18 levels (r=0.40, P=0.006), AST (r=0.40, P=0.007), ALT (r=0.71, P<0.0001) and GTT (r=0.28, P=0.06) levels. After adjustment for age and sex correlations persisted. Serum miR-122 levels were higher in severe steatosis group when compared to the other groups (P<0.05). CK-18 levels were higher in severe steatosis group when compared to subjects without steatosis (P<0.05). There was a positive correlation between miR-122 levels and HOMA-IR, whereas no correlation was found for CK18.

Conclusion: Already in prepubertal children, miR-122 levels were associated with measures of liver disease. Further studies will elucidate if miR-122 provides a useful biomarker for liver disease progression in children.

Funding: This project was supported by an ESPE-RU collaborative project grant.