Background

Relative to simple obesity (SO), non-alcoholic steatohepatitis (NASH) carries an increased risk of cardiovascular disease (CVD). Dysfunction of lipid metabolism is suggested as a potential a link. Distribution of both low density lipoprotein (LDL) and high density lipoprotein (HDL) more precisely reflects the atherogenity of lipids and improves CVD risk prediction beyond standard lipid risk markers. We hypothesized that the distribution of lipoprotein subfractions are more proatherogenic in children with NASH compared with SO.

Methods

We measured LDL and HDL subfractions in children (age: 8-17 yrs) with biopsy-proven NASH (n=11; NAS score>2) and SO (n=17; BMI>95th%) along with total cholesterol (TC), LDL, HDL, VLDL and IDL using the Lipoprint Lipoprotein Subfraction testing system.

Results

Children with NASH had significantly lower TC (p=0.04) and HDL, but higher non-HDL to HDL ratio (p=0.03) and similar VLDL and IDL concentrations compared to SO. While LDL1 and LDL2 were lower in NASH than SO (P<0.001), LDL3 (0.01) was higher. LDL4 was present only in NASH. The phenotypical pattern (an algorithmically derived factor based on particle size and weighted area% of individual subfractions of LDL), an indicator of risk for CVD, was found different in NASH compared with SO. All children with NASH, except one (intermediate), fit into pattern B phenotype (more atherogenic). The SO group fell into a mixed pattern consisting of 6 with pattern A (less atherogenic), 6 with intermediate pattern and 5 with pattern B. While children with NASH had lower large (HDL1,2&3) and intermediate (HDL4,5,6&7) subfractions (P<0.05 for both), the small subfractions (HDL8,9&10) were similar (P=0.28).

Conclusions

Children with NASH have different and more unfavorable distribution of HDL and LDL subparticles and LDL phenotype patterns compared to SO. The proatherogenic distribution of lipoprotein subfractions may contribute to increased propensity for CVD risk in NASH vs SO.