{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:20:53Z","timestamp":1784262053426,"version":"3.55.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to investigate the association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and NAFLD, as well as its relationship with hepatic steatosis and liver fibrosis, in a nationally representative sample of U.S. adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cross-sectional study analyzed data from 3,529 participants from the National Health and Nutrition Examination Survey in 2017\u20132020. Multivariable logistic regression and subgroup analyses were used to assess the association between NHHR and NAFLD. Multivariate linear regression was employed to evaluate the relationship between NHHR and hepatic steatosis (controlled attenuation parameter) and liver fibrosis (liver stiffness measurement). Nonlinear relationships were explored through fitted smoothing curves and threshold effect analysis. Receiver operating curve (ROC) analysis was performed to compare the diagnostic performance of NHHR with body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 3,529 participants (mean age: 51.34\u202fyears, 95% CI: 49.97, 52.72), with 53.53% male. NHHR showed a significant positive association with NAFLD after adjusting for confounders (OR: 1.33, 95% CI: 1.24, 1.42). Subgroup analysis indicated a stronger association in females and individuals with normal weight. A nonlinear relationship was identified, with a significant positive association below an inflection point of 4 (OR: 1.52, 95% CI: 1.38, 1.68). NHHR was positively associated with hepatic steatosis but not with liver fibrosis. For NAFLD diagnosis, NHHR achieved an area under the curve (AUC) of 0.66, outperforming TC (AUC\u202f=\u202f0.51) but indicating lower accuracy than BMI (AUC\u202f=\u202f0.77) and HDL-C (AUC\u202f=\u202f0.68).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NHHR is positively associated with NAFLD and hepatic steatosis in U.S. population, highlighting the important role of lipid control in the prevention and clinical management of NAFLD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1540903","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T04:10:37Z","timestamp":1744344637000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Association of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio with non-alcoholic fatty liver disease and hepatic steatosis in United States adults: insights from NHANES 2017\u20132020"],"prefix":"10.3389","volume":"12","author":[{"given":"Zhen","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Qi","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/s41575-021-00523-4","article-title":"Advancing the global public health agenda for NAFLD: a consensus statement","volume":"19","author":"Lazarus","year":"2022","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-alcoholic fatty liver disease - a global public health perspective","volume":"70","author":"Younossi","year":"2019","journal-title":"J Hepatol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"69","author":"Younossi","year":"2019","journal-title":"Hepatology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention","volume":"18","author":"Huang","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1042\/CS20220572","article-title":"Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways","volume":"136","author":"Badmus","year":"2022","journal-title":"Clin Sci (Lond)"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/s12944-019-1104-6","article-title":"Correlation of triglyceride to high-density lipoprotein cholesterol ratio with nonalcoholic fatty liver disease among the non-obese Chinese population with normal blood lipid levels: a retrospective cohort research","volume":"18","author":"Chen","year":"2019","journal-title":"Lipids Health Dis"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"101092","DOI":"10.1016\/j.molmet.2020.101092","article-title":"Dysregulated lipid metabolism links NAFLD to cardiovascular disease","volume":"42","author":"Deprince","year":"2020","journal-title":"Mol Metab"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.2147\/DMSO.S355980","article-title":"Utility of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio in evaluating incident diabetes risk","volume":"15","author":"Sheng","year":"2022","journal-title":"Diabetes Metab Syndr Obes"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"931","DOI":"10.5603\/KP.a2015.0086","article-title":"Lipoprotein ratios are better than conventional lipid parameters in predicting coronary heart disease in Chinese Han people","volume":"73","author":"Zhu","year":"2015","journal-title":"Kardiol Pol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/s12944-015-0023-4","article-title":"The value of the apoB\/apoA\u0399 ratio and the non-HDL-C\/HDL-C ratio in predicting carotid atherosclerosis among Chinese individuals with metabolic syndrome: a cross-sectional study","volume":"14","author":"Qin","year":"2015","journal-title":"Lipids Health Dis"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s12944-020-01336-1","article-title":"Importance of lipid ratios for predicting intracranial atherosclerotic stenosis","volume":"19","author":"Yang","year":"2020","journal-title":"Lipids Health Dis"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1186\/s12944-018-0848-8","article-title":"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","volume":"17","author":"Wang","year":"2018","journal-title":"Lipids Health Dis"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1186\/s12944-018-0720-x","article-title":"Higher non-HDL-cholesterol to HDL-cholesterol ratio linked with increased nonalcoholic steatohepatitis","volume":"17","author":"Wang","year":"2018","journal-title":"Lipids Health Dis"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s12944-020-01421-5","article-title":"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","volume":"19","author":"Yang","year":"2020","journal-title":"Lipids Health Dis"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1001\/jama.2012.40","article-title":"Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010","volume":"307","author":"Ogden","year":"2012","journal-title":"JAMA"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"100323","DOI":"10.1016\/j.jnha.2024.100323","article-title":"Association of visceral adiposity index with phenotypic age acceleration: insight from NHANES 1999-2010","volume":"28","author":"Xu","year":"2024","journal-title":"J Nutr Health Aging"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/S2468-1253(23)00066-3","article-title":"Non-invasive diagnosis and monitoring of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis","volume":"8","author":"Tincopa","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.cgh.2018.04.043","article-title":"Vibration-controlled transient Elastography to assess fibrosis and steatosis in patients with nonalcoholic fatty liver disease","volume":"17","author":"Siddiqui","year":"2019","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1016\/j.jand.2018.05.021","article-title":"Update of the healthy eating index: HEI-2015","volume":"118","author":"Krebs-Smith","year":"2018","journal-title":"J Acad Nutr Diet"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"l5584","DOI":"10.1136\/bmj.l5584","article-title":"Weight change across adulthood in relation to all cause and cause specific mortality: prospective cohort study","volume":"367","author":"Chen","year":"2019","journal-title":"BMJ"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"e127","DOI":"10.1016\/j.jacc.2017.11.006","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA guideline for the prevention, detection, evaluation, and Management of High Blood Pressure in adults: a report of the American College of Cardiology\/American Heart Association task force on clinical practice guidelines","volume":"71","author":"Whelton","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1001\/jama.2015.10029","article-title":"Prevalence of and trends in diabetes among adults in the United States, 1988-2012","volume":"314","author":"Menke","year":"2015","journal-title":"JAMA"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.molmet.2019.08.019","article-title":"PAR2 controls cholesterol homeostasis and lipid metabolism in nonalcoholic fatty liver disease","volume":"29","author":"Rana","year":"2019","journal-title":"Mol Metab"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"101109","DOI":"10.1016\/j.plipres.2021.101109","article-title":"Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis","volume":"83","author":"Li","year":"2021","journal-title":"Prog Lipid Res"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.numecd.2014.01.010","article-title":"Association of serum triglyceride-to-HDL cholesterol ratio with carotid artery intima-media thickness, insulin resistance and nonalcoholic fatty liver disease in children and adolescents","volume":"24","author":"Pacifico","year":"2014","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1097\/MPG.0000000000000584","article-title":"Improvement in liver histology is associated with reduction in dyslipidemia in children with nonalcoholic fatty liver disease","volume":"60","author":"Corey","year":"2015","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.jacl.2015.12.026","article-title":"Nonalcoholic fatty liver disease severity is associated with the ratios of total cholesterol and triglycerides to high-density lipoprotein cholesterol","volume":"10","author":"Wu","year":"2016","journal-title":"J Clin Lipidol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12944-019-0986-7","article-title":"Triglycerides to high-density lipoprotein cholesterol ratio as a surrogate for nonalcoholic fatty liver disease: a cross-sectional study","volume":"18","author":"Fan","year":"2019","journal-title":"Lipids Health Dis"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1038\/s41467-022-28138-6","article-title":"Formyl peptide receptor 2 determines sex-specific differences in the progression of nonalcoholic fatty liver disease and steatohepatitis","volume":"13","author":"Lee","year":"2022","journal-title":"Nat Commun"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2643","DOI":"10.1038\/s41591-023-02553-8","article-title":"Interaction between estrogen receptor-\u03b1 and PNPLA3 p.I148M variant drives fatty liver disease susceptibility in women","volume":"29","author":"Cherubini","year":"2023","journal-title":"Nat Med"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12944-021-01617-3","article-title":"Sex-specific contribution of lipid accumulation product and cardiometabolic index in the identification of nonalcoholic fatty liver disease among Chinese adults","volume":"21","author":"Liu","year":"2022","journal-title":"Lipids Health Dis"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1098078","DOI":"10.3389\/fendo.2023.1098078","article-title":"Remnant cholesterol, stronger than triglycerides, is associated with incident non-alcoholic fatty liver disease","volume":"14","author":"Cheng","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.3748\/wjg.v26.i15.1792","article-title":"Prevalence, clinical characteristics, risk factors, and indicators for lean Chinese adults with nonalcoholic fatty liver disease","volume":"26","author":"Zeng","year":"2020","journal-title":"World J Gastroenterol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s13104-018-3212-1","article-title":"Laboratory parameters in lean NAFLD: comparison of subjects with lean NAFLD with obese subjects without hepatic steatosis","volume":"11","author":"Bernhardt","year":"2018","journal-title":"BMC Res Notes"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s12944-021-01561-2","article-title":"The usefulness of obesity and lipid-related indices to predict the presence of non-alcoholic fatty liver disease","volume":"20","author":"Sheng","year":"2021","journal-title":"Lipids Health Dis"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1002\/hep4.1935","article-title":"Predicting NAFLD prevalence in the United States using National Health and nutrition examination survey 2017-2018 transient elastography data and application of machine learning","volume":"6","author":"Noureddin","year":"2022","journal-title":"Hepatol Commun"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","article-title":"Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease","volume":"75","author":"Ipsen","year":"2018","journal-title":"Cell Mol Life Sci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/s11883-022-01028-4","article-title":"Management of Dyslipidemia in patients with non-alcoholic fatty liver disease","volume":"24","author":"Martin","year":"2022","journal-title":"Curr Atheroscler Rep"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1210\/jc.2015-3111","article-title":"Hepatic steatosis and insulin resistance, but not steatohepatitis, promote Atherogenic dyslipidemia in NAFLD","volume":"101","author":"Bril","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/j.jacl.2017.02.001","article-title":"Relationship between noninvasive scores of nonalcoholic fatty liver disease and nuclear magnetic resonance lipoprotein abnormalities: a focus on atherogenic dyslipidemia","volume":"11","author":"Amor","year":"2017","journal-title":"J Clin Lipidol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"174","DOI":"10.3390\/antiox10020174","article-title":"Role of oxidative stress in the pathogenesis of non-alcoholic fatty liver disease: implications for prevention and therapy","volume":"10","author":"Arroyave-Ospina","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.freeradbiomed.2019.05.029","article-title":"Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease","volume":"144","author":"Svegliati-Baroni","year":"2019","journal-title":"Free Radic Biol Med"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1530\/EJE-20-1240","article-title":"Atherogenic dyslipidemia, but not hyperglycemia, is an independent factor associated with liver fibrosis in subjects with type 2 diabetes and NAFLD: a population-based study","volume":"184","author":"Juli\u00e1n","year":"2021","journal-title":"Eur J Endocrinol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"e13519","DOI":"10.1111\/eci.13519","article-title":"Nonalcoholic fatty liver disease or metabolic dysfunction-associated fatty liver disease diagnoses and cardiovascular diseases: from epidemiology to drug approaches","volume":"51","author":"Dongiovanni","year":"2021","journal-title":"Eur J Clin Investig"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1194\/jlr.P090449","article-title":"PCSK7 gene variation bridges atherogenic dyslipidemia with hepatic inflammation in NAFLD patients","volume":"60","author":"Dongiovanni","year":"2019","journal-title":"J Lipid Res"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1540903\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T04:10:38Z","timestamp":1744344638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1540903\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":46,"alternative-id":["10.3389\/fnut.2025.1540903"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1540903","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]},"article-number":"1540903"}}