In the present retrospective cohort study, we found for first time that a higher non-HDL-c/ HDL-c rate had a higher risk of NAFLD among children and adolescence. It is noteworthy that the mentioned relationship lasted when potential confounders were regulated. Moreover, the non-HDL-c/HDL-c rate a better predictive value for NAFLD than the non-HDL-c and HDL-c in both boys and girls. The findings of this study suggested that the non-HDL-c/HDL-c ratio may help early identify NALFD among children and adolescents.
Previous studies had confirmed that metabolic syndrome(MetS) and obesity are the major risk factors for paediatric NAFLD and dyslipidemia play a pivotal role in NAFLD pathogenesis[4, 15]. Recent clinical trials suggest that statin-based therapies (lipid-lowing drug statin treatment) could improve liver tests and live ultrasonographic evidence of NAFLD patients[16]. The dyslipidemia in NAFLD is characterized by elevated conditions of TG and dense low-density lipoprotein (LDL) particles and decreased conditions of low high-density lipoprotein (HDL) cholesterol[17]. In NAFLD, as driven by lipid metabolism abnormalities, excess fat undergoes accumulation in the hepatocytes. The mentioned intrahepatic lipid accumulating was attributed to decreased triglycerides (TG) export and significantly low density lipoprotein (VLDL) synthesis as well as liver free fatty acid (FFA) uptake [18, 19]. Ectopic lipid overloading in hepatocytes are associated with an induction of inflammation and oxidative stress, and the secreting of several cytokines (including adiponectin, interleukins (ILs) and tumor necrosis factor (TNF))[20]. Moreover, excess of FFAs form to fatty acyl-CoAs catalyzed by acetyl coenzyme A (acyl-CoA), thereby probably inducing β-oxidation pathways. The above inflammation, oxidative stress are involved in NAFLD initiation and progression [21, 22].
Non-HDL-c contains multiple lipoproteins(lipoprotein A, intermediate-density lipoprotein (IDL), low density lipoprotein (LDL) and very-low-density lipoprotein (VLDL)) and was demonstrated as a secondary targets for lipid-lowering therapy[23]. In comparison with the non-HDL-c, the non-HDL-c/HDL-c rate can cover more comprehensive abilities of lipid dysregulation and better for assessing lipid-related disease risk. Existing studies reported that non-HDL-c/HDL-c rate more effectively predicts CVD in type 2 diabetes than non-HDL-c[11], and the ratio exhibits higher predictive value than the apoB/apoA1 rate in terms of insulin resistance and MS[8]. Moreover, as revealed from a perspective cohort study, non-HDL-c/HDL-c rate outperforms non-HDL-c in predicting new-onset NAFLD in Chinese adult population[11]. Thus, the associations of the non-HDL-c/HDL-c rate and the risk of NAFLD among children and adolescence should be explored.
Dividing the baseline characteristical data of 7759 participants into tertiles according to non-HDL-c/HDL-c ratio, we found anthropometric variables such as ALT, TG, LDL, HBA1C(%), FBG were higher in the highest tertile than the lowest one, The similar results can be found in previous studies[24]. As expected, the incidence of obesity significantly increased across non-HDL-c/HDL-c tertiles. In addition, the prevalence of NAFLD increased as the tertiles of the non-HDL-c/HDL-c ratio rose. The binary logistics regression analysis suggested that higher non-HDL-c/HDL-c ratio was highly positively associated with an increased risk of NAFLD. In terms of gender distribution, Our study found the prevalence of NAFLD by gender was significant higher in boys compared to girls. The result of this study complies with Brunt EM et al.[25] and Welsh JA et al.[26], demonstrating that boys are more likely to develop NAFLD than girls. It has been indicated this phenomenon may be attributed to the potential protective role of estrogen against hepatic steatosis[27, 28].
The findings here are of certain clinical implications. We performed ROC curve analyses to explore the predictive value of the non-HDL-c/HDL-c ratio for NAFLD risk. Our findings suggest that the non-HDL-c/HDL-c ratio may serve as a more effective predictor for pediatric NAFLD than non-HDL-c and HDL-c. The optimal cutoff values of the non-HDL-c/HDL-c rate to identify NAFLD was 2.475 in boys and 2.695 in girls. Besides, the non-HDL-c/HDL-c rate exhibits simplicity and feasibility to determine. Accordingly, the non-HDL-c/HDL-c rate might feasibly achieve prediction and be used for screening for NALFD among children and adolescents.
Some limits are worth noting here. First, the diagnosis of NAFLD was performed using ultrasonography instead of liver biopsy (gold standard for diagnosing NAFLD) which is limited for its complications and invasiveness. However, the sensitivity of ultrasonography is low when NAFLD with fat contents less than 30%, thereby probably causing misdiagnosis[29]. Second, since this was a single center cohort study, largescale and multiple center studies should be conducted to confirm our conclusions of the present study. Third, this study had a retrospectively designing process, so the causality between non-HDL-c/HDL-c rate and NAFLD is not able to be overall set. The association requires confirmation by prospective retrospective study.