ESPE Abstracts

Background: The rs72613567:TA variant in the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene has been associated with decreased risk of liver damage.

Aims: To investigate the association between the HSD17B13 rs72613567:TA variant and both hepatic steatosis and biochemical markers of liver damage in obese children and to evaluate its potential effect in NAFLD genetic predisposition.

Methods: 684 obese children were genotyped for HSD17B13, patatin-like phospholipase domain containing 3 (PNPLA3) gene, transmembrane 6 superfamily member 2 (TM6SF2), and membrane bound O-acyltransferase domain containing 7 (MBOAT7) polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) was calculated. The population was clustered in two risk groups (group 1 including subjects carrying up to 3 risk alleles and group 2 including subjects carrying 4-6 risk alleles).

Results: Carriers of the HSD17B13 rare A allele showed lower serum ALT and AST levels than noncarriers, even after adjustments for confounding factors (A carriers ALT means±SD 26.58±18.02, noncarriers 31.83±20.64; P=0.001; A carriers AST means±SD 23.32±8.13, noncarrriers 25.75±9.66; P=0.001). Likewise, these patients showed a lower percentage of hepatic steatosis (carriers 27.1%, noncarriers 72.9%, P=0.0001) and a significant lower PNFI levels than noncarriers (A carriers mean±SD 7.57±2.94, noncarriers 7.99±2.35, P=0.04), even after adjustments for confounding factors (P=0.03).

Similar findings were confirmed in the study population stratified on the basis of the genetic risk score. In fact, both in the group 1 and 2, the patients carrying the HSD17B13 rare A allele presented a statistically significant lower serum ALT levels, PNFI levels, and a lower percentage of liver steatosis compared to noncarriers with the same genetic risk score.

Conclusion: We demonstrated in childhood obesity the protective effect of the rs72613567:TA variant in HSD17B13 gene in reducing liver damage in obese children even regardless of genetic predisposition.