{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T01:48:58Z","timestamp":1781920138298,"version":"3.54.5"},"reference-count":52,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T00:00:00Z","timestamp":1589760000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>The aim of this study was to analyze the utility of liver function tests (LFT) and fatty liver index (FLI), a surrogate marker of non-alcoholic fatty liver disease, in the categorization of metabolic phenotypes in a Mediterranean population. A cross-sectional study was performed on a random representative sample of 2233 adults assigned to a health center in M\u00e1laga, Spain. The metabolic phenotypes were determined based on body mass index (BMI) categorization and the presence or absence of two or more cardiometabolic abnormalities (high blood pressure, low high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, pre-diabetes) or type 2 diabetes. No difference was observed between metabolically healthy and metabolically abnormal phenotypes on LFT. The mean FLI of the population was 41.1 \u00b1 28.6. FLI was significantly higher (p &lt; 0.001) in the metabolically abnormal phenotypes in all BMI categories. The proportion of individuals with pathological FLI (\u226560) was significantly higher in the metabolically abnormal overweight and obese phenotypes (p &lt; 0.001). On a multivariate model adjusted for sex, age, and waist circumference, a significant correlation was found between pathological FLI and metabolically abnormal phenotypes in the overweight and obese BMI categories. Area under the curve (AUC) of FLI as a biomarker was 0.76, 0.74, and 0.72 for the metabolically abnormal normal-weight, overweight, and obese groups, respectively. Liver biochemistry is poorly correlated with metabolic phenotypes. Conversely, a good correlation between FLI, as a marker of non-alcoholic fatty liver disease (NAFLD), and metabolically abnormal phenotypes in all BMI ranges was found. Our study suggests that FLI may be a useful marker for characterizing metabolically abnormal phenotypes in individuals who are overweight or obese.<\/jats:p>","DOI":"10.3390\/ijerph17103518","type":"journal-article","created":{"date-parts":[[2020,5,18]],"date-time":"2020-05-18T11:34:14Z","timestamp":1589801654000},"page":"3518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Utility of Liver Function Tests and Fatty Liver Index to Categorize Metabolic Phenotypes in a Mediterranean Population"],"prefix":"10.3390","volume":"17","author":[{"given":"Dariusz","family":"Narankiewicz","sequence":"first","affiliation":[{"name":"Preventive Medicine Department, Virgen de la Victoria University Hospital, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefina","family":"Ruiz-Nava","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Regional University Hospital of M\u00e1laga, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Buonaiuto","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Regional University Hospital of M\u00e1laga, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Isabel","family":"Ruiz-Moreno","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Regional University Hospital of M\u00e1laga, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9333-076X","authenticated-orcid":false,"given":"Mar\u00eda Dolores","family":"L\u00f3pez-Carmona","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Regional University Hospital of M\u00e1laga, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis Miguel","family":"P\u00e9rez-Belmonte","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Regional University Hospital of M\u00e1laga, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"G\u00f3mez-Huelgas","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Regional University Hospital of M\u00e1laga, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), 29010 Malaga, Spain"},{"name":"Ciber Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n. Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Rosa","family":"Bernal-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Regional University Hospital of M\u00e1laga, Instituto de Investigaci\u00f3n Biom\u00e9dica de M\u00e1laga (IBIMA), 29010 Malaga, Spain"},{"name":"Ciber Fisiopatolog\u00eda de la Obesidad y Nutrici\u00f3n. Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.3748\/wjg.v24.i30.3361","article-title":"Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis","volume":"24","author":"Leoni","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic fatty liver disease. A systematic review","volume":"313","author":"Rinella","year":"2015","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1365-2036.2011.04724.x","article-title":"Systematic review: The epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults","volume":"34","author":"Vernon","year":"2011","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"112","DOI":"10.7326\/0003-4819-132-2-200001180-00004","article-title":"Prevalence of and risk factors for hepatic steatosis in Northern Italy","volume":"132","author":"Bellentani","year":"2000","journal-title":"Ann. Int. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.2337\/dc06-2247","article-title":"Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients","volume":"30","author":"Targher","year":"2007","journal-title":"Diabetes Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1053\/jhep.2003.50193","article-title":"Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference","volume":"37","author":"Caldwell","year":"2003","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3803\/EnM.2020.35.1.165","article-title":"Visceral-to-subcutaneous abdominal fat ratio is associated with nonalcoholic fatty liver disease and liver fibrosis","volume":"35","author":"Jung","year":"2020","journal-title":"Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"O\u2019Connell, J., Lynch, L., Cawood, T.J., Kwasnik, A., Nolan, N., Geoghegan, J., McCormick, A., O\u2019Farrelly, C., and O\u2019Shea, D. (2010). The relationship of omental and subcutaneous adipocyte size to metabolic disease in severe obesity. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009997"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4254\/wjh.v9.i16.715","article-title":"Non-alcoholic fatty liver disease: An expanded review","volume":"9","author":"Benedict","year":"2017","journal-title":"World J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s00018-018-2947-0","article-title":"Molecular pathways of nonalcoholic fatty liver disease development and progression","volume":"76","author":"Bessone","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"592404","DOI":"10.5402\/2011\/592404","article-title":"Obesity, Visceral Fat, and NAFLD: Querying the role of adipokines in the progression of nonalcoholic fatty liver disease","volume":"2011","author":"Mirza","year":"2011","journal-title":"ISRN Gastroenterol."},{"key":"ref_12","first-page":"1","article-title":"Triglyceride metabolism in the liver","volume":"8","author":"Cohen","year":"2017","journal-title":"Compr Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","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":"ref_14","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1053\/j.gastro.2009.06.005","article-title":"Prediction of non-alcoholic fatty liver disease and liver fat using metabolic and genetic factors","volume":"137","author":"Kotronen","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Italian Association for the Study of the Liver (AISF) (2017). AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions. Dig. Liver Dis., 49, 471\u2013483.","DOI":"10.1016\/j.dld.2017.01.147"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e000368","DOI":"10.1136\/bmjgast-2019-000368","article-title":"Effectiveness of phosphatidylcholine as adjunctive therapy in improving liver function tests in patients with non-alcoholic fatty liver disease and metabolic comorbidities: Real-life observational study from Russia","volume":"7","author":"Maev","year":"2020","journal-title":"BMJ Open Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"g4596","DOI":"10.1136\/bmj.g4596","article-title":"Non-alcoholic fatty liver disease","volume":"349","author":"Sattar","year":"2014","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1136\/gut.2010.216077","article-title":"Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease","volume":"59","author":"McPherson","year":"2010","journal-title":"Gut"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/cld.65","article-title":"Nonalcoholic fatty liver disease: Indications for liver biopsy and noninvasive biomarkers","volume":"1","author":"Noureddin","year":"2012","journal-title":"Clin. Liver Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., and Tiribelli, C. (2006). The Fatty Liver Index: A simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol., 6.","DOI":"10.1186\/1471-230X-6-33"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Brand\u00e3o, I., Martins, M.J., and Monteiro, R. (2020). Metabolically healthy obesity-heterogeneity in definitions and unconventional factors. Metabolites, 10.","DOI":"10.3390\/metabo10020048"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2388","DOI":"10.2337\/dc12-1971","article-title":"North West Adelaide Health Study TeamNorth West Adelaide health study team diabetes and cardiovascular disease outcomes in the metabolically healthy obese phenotype: A cohort study","volume":"36","author":"Appleton","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1111\/liv.14184","article-title":"Metabolically healthy versus unhealthy obesity and risk of fibrosis progression in non-alcoholic fatty liver disease","volume":"39","author":"Kim","year":"2019","journal-title":"Liver Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ecl.2004.03.005","article-title":"The metabolic syndrome: Prevalence in worlwide populations","volume":"33","author":"Cameron","year":"2004","journal-title":"Endocrinol. Metab. Clin. N Am."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1640","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":"ref_26","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2014). Standards of medical care in diabetes-2014. Diabetes Care, 37, S14\u2013S80.","DOI":"10.2337\/dc14-S014"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/978-1-4939-9442-7_11","article-title":"ROC Curves for the statistical analysis of microarray data","volume":"1986","author":"Cao","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1080\/10543406.2017.1377728","article-title":"Influence analysis for the area under the receiver operating characteristic curve","volume":"28","author":"Ke","year":"2018","journal-title":"J. Biopharm. Stat."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"57","DOI":"10.3748\/wjg.v19.i1.57","article-title":"Comparison of fatty liver index with noninvasive methods for steatosis detection and quantification","volume":"19","author":"Webb","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1682","DOI":"10.1097\/MD.0000000000001682","article-title":"Validation of the fatty liver index for nonalcoholic fatty liver disease in middle-aged and elderly Chinese","volume":"94","author":"Huang","year":"2015","journal-title":"Medicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1038\/ajg.2017.371","article-title":"Adherence to mediterranean diet and non-alcoholic fatty liver disease: Effect on insulin resistance","volume":"112","author":"Baratta","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15756","DOI":"10.1038\/s41598-017-15943-z","article-title":"PNPLA3 variant and portal\/periportal histological pattern in patients with biopsy-proven non-alcoholic fatty liver disease: A possible role for oxidative stress","volume":"7","author":"Carpino","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.atherosclerosis.2016.12.018","article-title":"Non-alcoholic fatty liver disease and subclinical atherosclerosis: A comparison of metabolically-versus genetically-driven excess fat hepatic storage","volume":"257","author":"Polimeni","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ejim.2012.02.016","article-title":"Metabolic syndrome and vascular risk estimation in a Mediterranean non-diabetic population without cardiovascular disease","volume":"23","author":"Mancera","year":"2012","journal-title":"Eur. J. Int. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cmet.2017.08.002","article-title":"Non-alcoholic fatty liver disease as a nexus of metabolic and hepatic diseases","volume":"27","author":"Samuel","year":"2018","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"21894","DOI":"10.1038\/srep21894","article-title":"Hepatic fat content is a determinant of metabolic phenotypes and increased carotid intima-media thickness in obese adults","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1007\/s10620-014-3214-3","article-title":"Serum alanine aminotransferase independently correlates with intrahepatic triglyceride contents in obese subjects","volume":"59","author":"Chen","year":"2014","journal-title":"Dig. Dis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1001\/archinte.168.15.1609","article-title":"Identification and characterization of metabolically benign obesity in humans","volume":"168","author":"Stefan","year":"2008","journal-title":"Arch Int. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1038\/ijo.2013.208","article-title":"Differences in body composition between metabolically healthy obese and metabolically abnormal obese adults","volume":"38","author":"Camhi","year":"2014","journal-title":"Int. J. Obes."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1159\/000471488","article-title":"The metabolic phenotype in obesity: Fat mass, body fat distribution, and adipose tissue function","volume":"10","author":"Goossens","year":"2017","journal-title":"Obes. Facts."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"124958","DOI":"10.1155\/2013\/124958","article-title":"Independent association between nonalcoholic fatty liver disease and cardiovascular disease: A systematic review and meta-analysis","volume":"2013","author":"Lu","year":"2013","journal-title":"Int. J. Endocrinol"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.metabol.2009.06.020","article-title":"Metabolically healthy but obese individuals: Relationship with hepatic enzymes","volume":"59","author":"Messier","year":"2010","journal-title":"Metabolism"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pajunen, P., Kotronen, A., Korpi-Hy\u00f6v\u00e4lti, E., Kein\u00e4nen-Kiukaanniemi, S., Oksa, H., Niskanen, L., Saaristo, T., Saltevo, J.T., Sundvall, J., and Vanhala, M. (2011). Metabolically healthy and unhealthy obesity phenotypes in the general population: The FIN-D2D Survey. BMC Public Health, 11.","DOI":"10.1186\/1471-2458-11-754"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12933-015-0306-0","article-title":"Combined influence of nonalcoholic fatty liver and body size phenotypes on diabetes risk","volume":"14","author":"Du","year":"2015","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3389\/fcvm.2020.00022","article-title":"Adipose tissue distribution, inflammation and its metabolic consequences, including diabetes and cardiovascular disease","volume":"7","author":"Chait","year":"2020","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.numecd.2013.12.002","article-title":"Current issues in the identification and treatment of metabolically healthy but obese individuals","volume":"24","author":"Plourde","year":"2014","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"758","DOI":"10.4158\/EP12355.OR","article-title":"Prevalence of metabolically discordant phenotypes in a mediterranean population-The IMAP study","volume":"19","author":"Narankiewicz","year":"2013","journal-title":"Endocr. Pract."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bozeman, S.R., Hoaglin, D.C., Burton, T.M., Pashos, C.L., Ben-Joseph, R.H., and Hollenbeak, C.S. (2012). Predicting waist circumference from body mass index. BMC Med. Res. Methodol., 12.","DOI":"10.1186\/1471-2288-12-115"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"210","DOI":"10.2337\/dc10-0665","article-title":"Prevalence, metabolic features, and prognosis of metabolically healthy obese Italian individuals: The Cremona Study","volume":"34","author":"Calori","year":"2011","journal-title":"Diabetes Care"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/hep.24452","article-title":"Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: A meta-analysis","volume":"54","author":"Hernaez","year":"2011","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"984","DOI":"10.2337\/db06-1256","article-title":"Serial metabolic measurements and conversion to type 2 diabetes in the west of Scotland coronary prevention study: Specific elevations in alanine aminotransferase and triglycerides suggest hepatic fat accumulation as a potential contributing factor","volume":"56","author":"Sattar","year":"2007","journal-title":"Diabetes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1530\/EJE-14-0112","article-title":"External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals","volume":"171","author":"Cuthbertson","year":"2014","journal-title":"Eur. J. Endocrinol."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/10\/3518\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:29:51Z","timestamp":1760174991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/10\/3518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,18]]},"references-count":52,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["ijerph17103518"],"URL":"https:\/\/doi.org\/10.3390\/ijerph17103518","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,18]]}}}