Introduction
Non-alcoholic fatty liver disease (NAFLD) is a common liver disease and a health threat in obese children.  In addition to obesity, previous studies have identified several risk factors for the development of NAFLD, including sex and metabolic aberrations.  Also, several genetic variants that predispose to the development of NAFLD, have been identified. However, it is not yet fully clear if the factors involved in the development of NAFLD differ between these genetic variants. The aim of this study was to identify determinants of alanine aminotransferase (ALT), as a marker for steatohepatitis, in a population of children with overweight and obesity, and to evaluate if these determinants differ depending on genetic predisposition.

Methods
One hundred and seventy-four children (49% boys) from the Centre for Overweight Adolescent and Children’s Healthcare (COACH) at the Maastricht University Medical Centre were included. PNPLA3 I148M genotypes were determined, as well as liver-related, anthropometric and cardiometabolic risk parameters.

Results
In the whole group, sex, total cholesterol levels, triglyceride levels, HOMA-IR and PNPLA3 risk alleles were all identified as significant predictors of logALT levels. Stratification for genotypes showed that sex and HOMA-IR were significant predictors in both children with and without the PNPLA3 risk allele. Interestingly, triglyceride levels were only a predictor for logALT levels in carriers of the PNPLA3 risk allele. ALT levels were significantly higher in PNPLA3 G allele carriers, despite a normal cardiometabolic risk profile. The percentage of children with ALT levels above the upper limit of normal was significantly higher in PNPLA3 risk allele carriers compared to non-carriers, while the percentage of children with triglyceride levels above normal was the same in both groups.

Conclusion
Determinants of ALT levels cannot be generalized across all children, but are genotype-specific. We also showed that metabolic parameters within the normal range are already associated with elevated ALT levels, in children with a genetic predisposition for developing NAFLD.

05 - EARLY DEVELOPMENT OF NAFLD IN GENETICALLY PREDISPOSED CHILDREN WITH OBESITY DOES NOT COINCIDE WITH METABOLIC DERANGEMENTS