Editor’s Note: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-quarter of the global adult population, imposing a significant health and economic burden. However, there are currently no approved treatments for MASLD, and screening strategies for high-risk groups—such as individuals with obesity and type 2 diabetes (T2D)—are inconsistently implemented in clinical practice, leading to a high rate of missed diagnoses.Non-high-density lipoprotein cholesterol (Non-HDL-C) is calculated by subtracting high-density lipoprotein cholesterol (HDL-C) from total cholesterol (TC). The ratio of Non-HDL-C to HDL-C (NHHR) is an emerging composite lipid marker. Previous studies have demonstrated that NHHR has strong predictive value for cardiovascular and cerebrovascular diseases, surpassing traditional lipid parameters.
Furthermore, research has shown that NHHR is an independent predictor of diabetes risk, likely due to the close interplay between lipid metabolism disorders, insulin resistance, and glucose metabolism dysregulation. However, to date, systematic studies evaluating NHHR’s predictive performance in individuals with or without T2D remain limited.
A recent study published in BMC Gastroenterology explored the association between NHHR and MASLD, specifically assessing its predictive value in obese and T2D populations.
The study analyzed data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES), initially including 9,254 participants. After excluding individuals with incomplete MASLD, HDL-C, or TC data, those with missing baseline covariates, individuals under 20 years old, and participants with extreme NHHR values (below the 1st percentile or above the 99th percentile), a total of 3,784 participants were included in the final analysis.
Participants were divided into three groups based on NHHR tertiles: the low NHHR group (T1, n = 1,261), the middle NHHR group (T2, n = 1,261), and the high NHHR group (T3, n = 1,262). There were no significant differences in age among the three groups. Compared with the low NHHR group, participants in the middle and high NHHR groups had higher prevalence rates of MASLD, hypertension, and T2D.
Association Between NHHR and MASLD
Multivariate logistic regression analysis consistently showed a strong positive association between NHHR and MASLD across all models. In the fully adjusted model (Model 2), each unit increase in NHHR was associated with a 26% higher risk of MASLD (OR = 1.26, 95% CI: 1.18–1.35, P < 0.001). Compared with the middle NHHR group, the high NHHR group had a significantly higher prevalence of MASLD (OR = 1.97, 95% CI: 1.62–2.41, P < 0.001). Additionally, smooth curve fitting analysis further confirmed the positive correlation between NHHR and MASLD.
Subgroup Analysis
Subgroup analysis (Figure 2) demonstrated a significant positive correlation between NHHR and MASLD across all subgroups, including those stratified by age, sex, BMI, and T2D status. However, interaction tests for the BMI and T2D subgroups suggested that the association between NHHR and MASLD might be stronger in non-obese individuals (BMI < 30 kg/m²) and those without T2D (P < 0.05 for both interactions). These findings indicate that NHHR is an independent predictor of MASLD, unaffected by BMI and T2D. Notably, the prevalence of MASLD was higher in non-obese individuals, potentially due to increased visceral fat deposition in non-obese MASLD patients.
Conclusion
This cross-sectional study identified a significant linear positive association between NHHR and MASLD, a relationship that remained robust across different age, sex, BMI, and T2D subgroups. These findings suggest that NHHR has potential as a predictive marker for MASLD screening in individuals with obesity or T2D. Future studies using gold-standard diagnostic methods are needed to validate these findings. Additionally, further research should explore the underlying mechanisms linking NHHR to MASLD and assess its predictive value in other populations.
