{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:36:37Z","timestamp":1762176997290,"version":"3.37.3"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T00:00:00Z","timestamp":1501113600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T00:00:00Z","timestamp":1501113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>Healthy volunteers are crucial for biomedical research. Inadvertent inclusion of subjects with nonalcoholic fatty liver disease (NAFLD) as controls can compromise study validity and subject safety. Given the rising prevalence of NAFLD in the general population, we sought to identify its prevalence and potential impact in volunteers for clinical trials. We conducted a cross\u2010sectional study of subjects who were classified as healthy volunteers between 2011 and 2015 and had no known liver disease. Subjects were classified as presumed NAFLD (pNF; alanine aminotransferase [ALT] level\u2009\u2265\u200920 for women or\u2009\u2265\u200931 for men and body mass index [BMI]\u2009&gt;\u200925\u2009kg\/m<jats:sup>2<\/jats:sup>), healthy non\u2010NAFLD controls (normal ALT and BMI), or indeterminate. A total of 3160 subjects participated as healthy volunteers in 149 clinical trials (1\u201029 trials per subject); 1732 of these subjects (55%) had a BMI\u2009&gt;\u200925\u2009kg\/m<jats:sup>2<\/jats:sup> and 1382 (44%) had abnormal ALT. pNF was present in 881 subjects (27.9%), and these subjects were older than healthy control subjects and had higher triglycerides, low\u2010density lipoprotein cholesterol, and HbA1c and lower high\u2010density lipoprotein cholesterol (<jats:italic toggle=\"yes\">P<\/jats:italic>\u2009&lt;\u20090.001 for all). The 149 trials included 101 non\u2010interventional, 33 interventional, and 15 vaccine trials. The impact on study validity of recruiting NAFLD subjects as controls was estimated as likely, probable, and unlikely in 10, 41, and 98 trials, respectively. The proportion of pNF subjects (28%\u201029%) did not differ by impact. Only 14% of trials used both BMI and ALT for screening. ALT cutoffs for screening were based on local reference values. Grade 3\u20104 ALT elevations during the study period were rare but more common in pNF subjects than in healthy control subjects (4 versus 1). <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: NAFLD is common and often overlooked in volunteers for clinical trials, despite its potential impact on subject safety and validity of study findings. Increased awareness of NAFLD prevalence and stricter ALT cutoffs may ameliorate this problem. (H<jats:sc>epatology<\/jats:sc> 2017;66:825\u2013833)<\/jats:p>","DOI":"10.1002\/hep.29247","type":"journal-article","created":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T23:36:43Z","timestamp":1493854603000},"page":"825-833","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":29,"title":["How healthy are the \u201cHealthy volunteers\u201d? Penetrance of NAFLD in the biomedical research volunteer pool"],"prefix":"10.1097","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2895-3095","authenticated-orcid":false,"given":"Varun","family":"Takyar","sequence":"first","affiliation":[{"name":"Liver & Energy Metabolism Unit,Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health,Bethesda,MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand","family":"Nath","sequence":"additional","affiliation":[{"name":"Liver & Energy Metabolism Unit,Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health,Bethesda,MD"},{"name":"Department of Medicine,Medstar Washington Hospital Center,Washington,DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Beri","sequence":"additional","affiliation":[{"name":"Laboratory for Informatics Development,Biomedical Translational Research Information System, Clinical Center, National Institutes of Health,Bethesda,MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed M.","family":"Gharib","sequence":"additional","affiliation":[{"name":"Biomedical and Metabolic Imaging Branch, National Institute of Diabetes and Digestive and Kidney Diseases,Bethesda,MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaron","family":"Rotman","sequence":"additional","affiliation":[{"name":"Liver & Energy Metabolism Unit,Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health,Bethesda,MD"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2017,7,27]]},"reference":[{"key":"hep29247-bib-0001-20241017","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1053\/j.gastro.2012.04.001","article-title":"The diagnosis and management of non\u2010alcoholic fatty liver 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