Non‑high‑density lipoprotein cholesterol to high‑density lipoprotein cholesterol ratio as a biomarker for liver health: Insights from National Health and Nutrition Examination Survey data

Hong,Liekai; Sun,Yifan; Lu,Xiaojia; Xu,Xinwu

doi:10.3892/br.2025.1939

Non‑high‑density lipoprotein cholesterol to high‑density lipoprotein cholesterol ratio as a biomarker for liver health: Insights from National Health and Nutrition Examination Survey data

Authors:
- Liekai Hong
- Yifan Sun
- Xiaojia Lu
- Xinwu Xu
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Affiliations: Department of Cardiology, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515000, P.R. China, Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515000, P.R. China
Published online on: February 7, 2025 https://doi.org/10.3892/br.2025.1939
Article Number: 61
Copyright: © Hong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The non‑high‑density lipoprotein cholesterol to high‑density lipoprotein cholesterol ratio (NHHR), a lipid‑related biomarker, remains underexplored in relation to the risk of advanced fibrosis and hepatic steatosis. The present study aimed to investigate the potential association between the NHHR and these hepatic conditions. A total of 6,907 individuals aged 20 years and older from the National Health and Nutrition Examination Survey 2017‑2020 were included in the present study. Advanced fibrosis and hepatic steatosis were assessed using hepatic vibration‑controlled transient elastography. Multivariate regression analysis and subgroup analysis were performed to explore the independent association between the NHHR and the presence of advanced fibrosis and hepatic steatosis. Among the 6,907 adults included in the present study (mean age, 50.56±17.21 years; 3,398 male patients and 3,509 female patients), 409 (5.92%) were diagnosed with advanced fibrosis and 3,034 (43.93%) were diagnosed with hepatic steatosis. Following multivariable adjustment (age, sex, ethnicity, education level, family income‑to‑poverty ratio, smoking status, alcohol use and vigorous physical activity), logistic regression analysis demonstrated that an elevated NHHR was positively associated with increased possibility for advanced fibrosis [odds ratio (OR), 1.10; 95% confidence interval (CI), 1.03‑1.17; P=0.005]. The restricted cubic spline model indicated a linear dose‑response association between the NHHR and advanced fibrosis. The NHHR also exhibited a significant association with a higher risk of hepatic steatosis after full adjustment for covariates (OR, 1.61; 95% CI, 1.53‑1.68; P<0.001). Using a two‑segment linear regression model, an S‑shaped relationship was identified between the NHHR and hepatic steatosis, with an inflection point at 3.83. In conclusion, the present study established a robust association of the NHHR with advanced fibrosis and hepatic steatosis. The NHHR may serve as a straightforward anthropometric index for predicting these conditions.

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1	Estes C, Razavi H, Loomba R, Younossi Z and Sanyal AJ: Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 67:123–133. 2018.PubMed/NCBI View Article : Google Scholar
2	Le P, Chaitoff A, Rothberg MB, McCullough A, Gupta NM and Alkhouri N: Population-based trends in prevalence of nonalcoholic fatty liver disease in US adults with type 2 diabetes. Clin Gastroenterol Hepatol. 17:2377–2378. 2019.PubMed/NCBI View Article : Google Scholar
3	European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO clinical practice guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 81:492–542. 2024.PubMed/NCBI View Article : Google Scholar
4	Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, Kleiner DE and Loomba R: AASLD practice guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 77:1797–1835. 2023.PubMed/NCBI View Article : Google Scholar
5	European Association for the Study of the Liver; Clinical Practice Guideline Panel; Chair:; EASL Governing Board representative:; Panel members. EASL clinical practice guidelines on non-invasive tests for evaluation of liver disease severity and prognosis-2021 update. J Hepatol. 75:659–689. 2021.PubMed/NCBI View Article : Google Scholar
6	Eddowes PJ, Sasso M, Allison M, Tsochatzis E, Anstee QM, Sheridan D, Guha IN, Cobbold JF, Deeks JJ, Paradis V, et al: Accuracy of fibroscan controlled attenuation parameter and liver stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology. 156:1717–1730. 2019.PubMed/NCBI View Article : Google Scholar
7	Vilar-Gomez E, Vuppalanchi R, Gawrieh S, Samala N and Chalasani N: CAP and LSM as determined by VCTE are independent predictors of all-cause mortality in the US adult population. Hepatology. 77:1241–1252. 2023.PubMed/NCBI View Article : Google Scholar
8	Yu H, Huang Y, Li M, Jiang H, Yang B, Xi X, Smayi A, Wu B and Yang Y: Prognostic significance of dynamic changes in liver stiffness measurement in patients with chronic hepatitis B and compensated advanced chronic liver disease. J Gastroenterol Hepatol. 39:2169–2181. 2024.PubMed/NCBI View Article : Google Scholar
9	Hong H, He Y, Gong Z, Feng J and Qu Y: The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and kidney stones: A cross-sectional study. Lipids Health Dis. 23(102)2024.PubMed/NCBI View Article : Google Scholar
10	Lin W, Luo S, Li W, Liu J, Zhou T, Yang F, Zhou D, Liu Y, Huang W, Feng Y and Luo J: Association between the non-HDL-cholesterol to HDL- cholesterol ratio and abdominal aortic aneurysm from a Chinese screening program. Lipids Health Dis. 22(187)2023.PubMed/NCBI View Article : Google Scholar
11	Tan MY, Weng L, Yang ZH, Zhu SX, Wu S and Su JH: The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio with type 2 diabetes mellitus: Recent findings from NHANES 2007-2018. Lipids Health Dis. 23(151)2024.PubMed/NCBI View Article : Google Scholar
12	Hou K, Song W, He J and Ma Z: The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and prevalence of periodontitis among US adults: A cross-sectional NHANES study. Sci Rep. 14(5558)2024.PubMed/NCBI View Article : Google Scholar
13	Qi X, Wang S, Huang Q, Chen X, Qiu L, Ouyang K and Chen Y: The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and risk of depression among US adults: A cross-sectional NHANES study. J Affect Disord. 344:451–457. 2024.PubMed/NCBI View Article : Google Scholar
14	Yang S, Zhong J, Ye M, Miao L, Lu G, Xu C, Xue Z and Zhou X: Association between the non-HDL-cholesterol to HDL-cholesterol ratio and non-alcoholic fatty liver disease in Chinese children and adolescents: A large single-center cross-sectional study. Lipids Health Dis. 19(242)2020.PubMed/NCBI View Article : Google Scholar
15	Ciardullo S and Perseghin G: Statin use is associated with lower prevalence of advanced liver fibrosis in patients with type 2 diabetes. Metabolism. 121(154752)2021.PubMed/NCBI View Article : Google Scholar
16	Vilar-Gomez E, Nephew LD, Vuppalanchi R, Gawrieh S, Mladenovic A, Pike F, Samala N and Chalasani N: High-quality diet, physical activity, and college education are associated with low risk of NAFLD among the US population. Hepatology. 75:1491–1506. 2022.PubMed/NCBI View Article : Google Scholar
17	Yu H, Li M, Yang B, Sun H, Jiang H, Liang Z, Smayi A, Wu B and Yang Y: Proton pump inhibitor use is associated with increased liver steatosis. Biomed Rep. 21(116)2024.PubMed/NCBI View Article : Google Scholar
18	Leung CW and Tapper EB: Sugar-sweetened beverages are associated with increased liver stiffness and steatosis among apparently healthy adults in the United States. Clin Gastroenterol Hepatol. 20:959–961.e1. 2022.PubMed/NCBI View Article : Google Scholar
19	Ruan Z, Lu T, Chen Y, Yuan M, Yu H, Liu R and Xie X: Association between psoriasis and nonalcoholic fatty liver disease among outpatient US adults. JAMA Dermatol. 158:745–753. 2022.PubMed/NCBI View Article : Google Scholar
20	Siddiqui MS, Vuppalanchi R, Van Natta ML, Hallinan E, Kowdley KV, Abdelmalek M, Neuschwander-Tetri BA, Loomba R, Dasarathy S, Brandman D, et al: Vibration-Controlled transient elastography to assess fibrosis and steatosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 17:156–163.e2. 2019.PubMed/NCBI View Article : Google Scholar
21	Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, Romero D, Abdelmalek MF, Anstee QM, Arab JP, et al: A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Ann Hepatol. 29(101133)2024.PubMed/NCBI View Article : Google Scholar
22	Loomba R, Friedman SL and Shulman GI: Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell. 184:2537–2564. 2021.PubMed/NCBI View Article : Google Scholar
23	Lotta LA, Gulati P, Day FR, Payne F, Ongen H, van de Bunt M, Gaulton KJ, Eicher JD, Sharp SJ, Luan J, et al: Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nat Genet. 49:17–26. 2017.PubMed/NCBI View Article : Google Scholar
24	Petersen KF, Oral EA, Dufour S, Befroy D, Ariyan C, Yu C, Cline GW, DePaoli AM, Taylor SI, Gorden P and Shulman GI: Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest. 109:1345–1350. 2002.PubMed/NCBI View Article : Google Scholar
25	Kelley DE, McKolanis TM, Hegazi RA, Kuller LH and Kalhan SC: Fatty liver in type 2 diabetes mellitus: Relation to regional adiposity, fatty acids, and insulin resistance. Am J Physiol Endocrinol Metab. 285:E906–E916. 2003.PubMed/NCBI View Article : Google Scholar
26	Wueest S, Item F, Lucchini FC, Challa TD, Müller W, Blüher M and Konrad D: Mesenteric fat lipolysis mediates obesity-associated hepatic steatosis and insulin resistance. Diabetes. 65:140–148. 2016.PubMed/NCBI View Article : Google Scholar
27	Caussy C, Tripathi A, Humphrey G, Bassirian S, Singh S, Faulkner C, Bettencourt R, Rizo E, Richards L, Xu ZZ, et al: A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease. Nat Commun. 10(1406)2019.PubMed/NCBI View Article : Google Scholar
28	Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, et al: 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur Heart J. 41:111–188. 2020.PubMed/NCBI View Article : Google Scholar
29	Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, DeFronzo RA, Einhorn D, Fonseca VA, et al: Consensus statement by the American Association of Clinical Endocrinologists and American College Of Endocrinology on the comprehensive type 2 diabetes management algorithm-2019 executive summary. Endocr Pract. 25:69–100. 2019.PubMed/NCBI View Article : Google Scholar
30	Wang K, Shan S, Zheng H, Zhao X, Chen C and Liu C: Non-HDL-cholesterol to HDL-cholesterol ratio is a better predictor of new-onset non-alcoholic fatty liver disease than non-HDL-cholesterol: A cohort study. Lipids Health Dis. 17(196)2018.PubMed/NCBI View Article : Google Scholar