{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:53:22Z","timestamp":1784735602730,"version":"3.55.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) are important predictive factors for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to analyze the association between the ALT\/HDL-C ratio and NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a retrospective analysis of data from 14,251 individuals participating in the NAGALA project\u2019s health screening program. The presence of NAFLD was diagnosed based on the participants\u2019 alcohol consumption status and liver ultrasonography images. Multivariable logistic regression models were used to assess the association between the ALT\/HDL-C ratio and NAFLD. Receiver operating characteristic (ROC) analysis was performed to determine and compare the effectiveness of ALT, HDL-C, the aspartate aminotransferase to HDL-C (AST\/HDL-C) ratio, the gamma-glutamyl transferase to HDL-C (GGT\/HDL-C) ratio and the ALT\/HDL-C ratio in identifying NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed a significant positive association between the ALT\/HDL-C ratio and the prevalence of NAFLD. For each standard deviation (SD) increase in the ALT\/HDL-C ratio, the adjusted odds ratio (OR) for NAFLD among the participants was 3.05 [95% confidence interval (CI): 2.63, 3.53], with the highest quartile of ALT\/HDL-C ratio having a 9.96-fold increased risk compared to the lowest quartile. In further subgroup analyses stratified by gender, age, and waist circumference (WC), we observed a significantly higher risk of NAFLD associated with the ALT\/HDL-C ratio among individuals aged \u226545 years, males, and those who were abdominal obesity. Furthermore, based on the results of ROC analysis, we found that the ALT\/HDL-C ratio [area under the curves (AUC): 0.8553] was significantly superior to ALT, HDL-C, AST\/HDL-C ratio and GGT\/HDL-C ratio in identifying NAFLD (All Delong <jats:italic>P<\/jats:italic>&amp;lt;0.05); the threshold of suggested ALT\/HDL-C ratio for identifying NAFLD was 15.97.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This population-based study demonstrates a positive association between the ALT\/HDL-C ratio and NAFLD. The ALT\/HDL-C ratio can effectively identify individuals with NAFLD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1239398","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T14:39:17Z","timestamp":1693579157000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["The newly proposed alanine aminotransferase to high-density lipoprotein cholesterol ratio has shown effectiveness in identifying non-alcoholic fatty liver disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Jiajun","family":"Qiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maobin","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiming","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guotai","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.01.052","article-title":"Nonalcoholic fatty liver disease 2020: the state of the disease","volume":"158","author":"Cotter","year":"2020","journal-title":"Gastroenterology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23527","article-title":"The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis","volume":"51","author":"Ascha","year":"2010","journal-title":"Hepatology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26717","article-title":"Extrahepatic complications of nonalcoholic fatty liver disease","volume":"59","author":"Armstrong","year":"2014","journal-title":"Hepatology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012","article-title":"NAFLD: a multisystem disease","volume":"62","author":"Byrne","year":"2015","journal-title":"J Hepatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1080\/03602532.2017.1293683","article-title":"Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters","volume":"49","author":"Cobbina","year":"2017","journal-title":"Drug Metab Rev"},{"key":"B8","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1186\/s12967-023-04367-1","article-title":"Mitochondrial metabolic dysfunction and non-alcoholic fatty liver disease: new insights from pathogenic mechanisms to clinically targeted therapy","volume":"21","author":"Zheng","year":"2023","journal-title":"J Transl Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201900043","article-title":"Mitochondria-mediated pathogenesis and therapeutics for non-alcoholic fatty liver disease","volume":"63","author":"Li","year":"2019","journal-title":"Mol Nutr Food Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112041","article-title":"The role of mitochondria dysfunction and hepatic senescence in NAFLD development and progression","volume":"142","author":"Dabravolski","year":"2021","journal-title":"BioMed Pharmacother"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v21.i3.711","article-title":"Liver enzymes, metabolomics and genome-wide association studies: from systems biology to the personalized medicine","volume":"21","author":"Sookoian","year":"2015","journal-title":"World J Gastroenterol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B0720016","article-title":"Relationship between alanine aminotransferase levels and metabolic syndrome in nonalcoholic fatty liver disease","volume":"9","author":"Chen","year":"2008","journal-title":"J Zhejiang Univ Sci B"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.666","article-title":"Alanine aminotransferase as a marker of non-alcoholic fatty liver disease in relation to type 2 diabetes mellitus and cardiovascular disease","volume":"22","author":"Schindhelm","year":"2006","journal-title":"Diabetes Metab Res Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.11-27","article-title":"Serum alanine aminotransferase concentration as a predictive factor for the development or regression of fatty liver","volume":"49","author":"Omagari","year":"2011","journal-title":"J Clin Biochem Nutr"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2006.081257","article-title":"Higher concentrations of alanine aminotransferase within the reference interval predict nonalcoholic fatty liver disease","volume":"53","author":"Chang","year":"2007","journal-title":"Clin Chem"},{"key":"B16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.pcad.2015.05.004","article-title":"High-density lipoprotein function measurement in human studies: focus on cholesterol efflux capacity","volume":"58","author":"Rohatgi","year":"2015","journal-title":"Prog Cardiovasc Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136949","article-title":"Mitochondrial lipid homeostasis at the crossroads of liver and heart diseases","volume":"22","author":"Dabravolski","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8120625","article-title":"HDL-mediated cholesterol efflux and plasma loading capacities are altered in subjects with metabolically- but not genetically driven non-alcoholic fatty liver disease (NAFLD)","volume":"8","author":"Di Costanzo","year":"2020","journal-title":"Biomedicines"},{"key":"B19","doi-asserted-by":"publisher","first-page":"11691","DOI":"10.1038\/s41598-018-29639-5","article-title":"Impaired HDL cholesterol efflux capacity in patients with non-alcoholic fatty liver disease is associated with subclinical atherosclerosis","volume":"8","author":"Fadaei","year":"2018","journal-title":"Sci Rep"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1016\/j.cgh.2013.08.014","article-title":"Management of dyslipidemia as a cardiovascular risk factor in individuals with nonalcoholic fatty liver disease","volume":"12","author":"Corey","year":"2014","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-022-00868-3","article-title":"Lifestyle and metabolic factors for nonalcoholic fatty liver disease: Mendelian randomization study","volume":"37","author":"Yuan","year":"2022","journal-title":"Eur J Epidemiol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s12902-023-01382-7","article-title":"The nonlinear correlation between alanine aminotransferase to high-density lipoprotein cholesterol ratio and the risk of diabetes: a historical Japanese cohort study","volume":"23","author":"Cao","year":"2023","journal-title":"BMC Endocr Disord"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.5061\/dryad.8q0p192","article-title":"Data from: ectopic fat obesity presents the greatest risk for incident type 2 diabetes: a population-based longitudinal study","author":"Okamura","year":"2019"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-018-0076-3","article-title":"Ectopic fat obesity presents the greatest risk for incident type 2 diabetes: a population-based longitudinal study","volume":"43","author":"Okamura","year":"2019","journal-title":"Int J Obes (Lond)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2020.0163","article-title":"The effect of moderate alcohol drinking in nonalcoholic fatty liver disease","volume":"26","author":"Choi","year":"2020","journal-title":"Clin Mol Hepatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12786","article-title":"Modest alcohol consumption reduces the incidence of fatty liver in men: a population-based large-scale cohort study","volume":"30","author":"Hashimoto","year":"2015","journal-title":"J Gastroenterol Hepatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.192644","article-title":"Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity","volume":"120","author":"Alberti","year":"2009","journal-title":"Circulation"},{"key":"B28","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01526.x","article-title":"The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation","volume":"102","author":"Hamaguchi","year":"2007","journal-title":"Am J Gastroenterol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)30082-2","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI): an extension of the STROBE statement for neonatal infection research","volume":"16","author":"Fitchett","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4097\/kja.19087","article-title":"Multicollinearity and misleading statistical results","volume":"72","author":"Kim","year":"2019","journal-title":"Korean J Anesthesiol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.genm.2011.02.004","article-title":"World Health Day 2012 focuses on ageing and health","volume":"18","author":"Arabic","year":"2012","journal-title":"East Mediterr Health J"},{"key":"B33","doi-asserted-by":"crossref","DOI":"10.2307\/2531595","article-title":"Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach","volume":"44","author":"DeLong","year":"1988","journal-title":"Biometrics"},{"key":"B34","doi-asserted-by":"publisher","first-page":"27","DOI":"10.3350\/kjhep.2011.17.1.27","article-title":"Association of serum alanine aminotransferase and \u03b3-glutamyltransferase levels within the reference range with metabolic syndrome and nonalcoholic fatty liver disease","volume":"17","author":"Oh","year":"2011","journal-title":"Korean J Hepatol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23505","article-title":"Estimation of the healthy upper limits for serum alanine aminotransferase in Asian populations with normal liver histology","volume":"51","author":"Lee","year":"2010","journal-title":"Hepatology"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2012.07143.x","article-title":"Upper limit of normal serum alanine and aspartate aminotransferase levels in Korea","volume":"28","author":"Sohn","year":"2013","journal-title":"J Gastroenterol Hepatol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12293","article-title":"Upper limit of normal serum alanine aminotransferase levels in Japanese subjects","volume":"44","author":"Tanaka","year":"2014","journal-title":"Hepatol Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24725","article-title":"Upper limits of normal for alanine aminotransferase activity in the United States population","volume":"55","author":"Ruhl","year":"2012","journal-title":"Hepatology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e43736","DOI":"10.1371\/journal.pone.0043736","article-title":"Upper limits of normal for serum alanine aminotransferase levels in Chinese Han population","volume":"7","author":"Zheng","year":"2012","journal-title":"PloS One"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2006.11.007","article-title":"Effect of waist circumference on reference intervals of liver-related enzyme tests in apparently healthy adult Mexican Americans, black and white Americans","volume":"40","author":"Samadi","year":"2007","journal-title":"Clin Biochem"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1695874","article-title":"Alanine aminotransferase and body composition in obese men and women","volume":"2019","author":"Bekkelund","year":"2019","journal-title":"Dis Markers"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a008686","article-title":"Sex difference in high density lipoprotein cholesterol in six countries","volume":"143","author":"Davis","year":"1996","journal-title":"Am J Epidemiol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1007\/BF02265258","article-title":"Sex difference in the regulation of plasma high density lipoprotein cholesterol by genetic and environmental factors","volume":"97","author":"Kauma","year":"1996","journal-title":"Hum Genet"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2006.00636.x","article-title":"Low serum high-density lipoprotein cholesterol in obese subjects with normal serum triglycerides: the role of insulin resistance and inflammatory cytokines","volume":"9","author":"Mooradian","year":"2007","journal-title":"Diabetes Obes Metab"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2015.02.262","article-title":"Effects of menopause, gender and age on lipids and high-density lipoprotein cholesterol subfractions","volume":"81","author":"Anagnostis","year":"2015","journal-title":"Maturitas"},{"key":"B46","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.cgh.2011.10.014","article-title":"Serum levels of alanine aminotransferase decrease with age in longitudinal analysis","volume":"10","author":"Dong","year":"2012","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0014254","article-title":"Alanine aminotransferase decreases with age: the Rancho Bernardo Study","volume":"5","author":"Dong","year":"2010","journal-title":"PloS One"},{"key":"B48","doi-asserted-by":"publisher","first-page":"798","DOI":"10.2105\/ajph.86.6.798","article-title":"Age-related changes in total and high-density-lipoprotein cholesterol in elderly Dutch men","volume":"86","author":"Weijenberg","year":"1996","journal-title":"Am J Public Health"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10215118","article-title":"Association of serum high-density lipoprotein cholesterol with high blood pressures at checkup: results of kanagawa investigation of total checkup data from the national database-9 (KITCHEN-9)","volume":"10","author":"Nakajima","year":"2021","journal-title":"J Clin Med"},{"key":"B50","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s13148-019-0767-1","article-title":"Epigenetic age acceleration and metabolic syndrome in the coronary artery risk development in young adults study","volume":"11","author":"Nannini","year":"2019","journal-title":"Clin Epigenet"},{"key":"B51","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.phrs.2017.03.008","article-title":"Sex- and gender-related prevalence, cardiovascular risk and therapeutic approach in metabolic syndrome: A review of the literature","volume":"120","author":"Pucci","year":"2017","journal-title":"Pharmacol Res"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/nu15020257","article-title":"Waist circumference is an essential factor in predicting insulin resistance and early detection of metabolic syndrome in adults","volume":"15","author":"Ram\u00edrez-Manent","year":"2023","journal-title":"Nutrients"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9030242","article-title":"Obesity affects HDL metabolism, composition and subclass distribution","volume":"9","author":"Stadler","year":"2021","journal-title":"Biomedicines"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.327.7423.1082","article-title":"Liver damage and protective effect of high density lipoprotein cholesterol","volume":"327","author":"Salonen","year":"2003","journal-title":"BMJ"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1053\/j.gastro.2013.08.036","article-title":"Association between high-normal levels of alanine aminotransferase and risk factors for atherogenesis","volume":"145","author":"Siddiqui","year":"2013","journal-title":"Gastroenterology"},{"key":"B56","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1210\/er.2015-1137","article-title":"Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus","volume":"37","author":"Kautzky-Willer","year":"2016","journal-title":"Endocr Rev"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/3920196","article-title":"The intricate relationship between type 2 diabetes mellitus (T2DM), insulin resistance (IR), and nonalcoholic fatty liver disease (NAFLD)","volume":"2020","author":"Tanase","year":"2020","journal-title":"J Diabetes Res"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00003-1","article-title":"A global view of the interplay between non-alcoholic fatty liver disease and diabetes","volume":"10","author":"Stefan","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i23.7392","article-title":"Radiologic evaluation of nonalcoholic fatty liver disease","volume":"20","author":"Lee","year":"2014","journal-title":"World J Gastroenterol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1239398\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T14:39:23Z","timestamp":1693579163000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1239398\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,31]]},"references-count":59,"alternative-id":["10.3389\/fendo.2023.1239398"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1239398","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,31]]},"article-number":"1239398"}}