{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:11:00Z","timestamp":1772169060255,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.14974.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000}}],"reference-count":50,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["G0801456"],"award-info":[{"award-number":["G0801456"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_UU_12013\/5"],"award-info":[{"award-number":["MC_UU_12013\/5"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P014437\/1"],"award-info":[{"award-number":["MR\/P014437\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["NF-SI-0611-10196"],"award-info":[{"award-number":["NF-SI-0611-10196"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203738"],"award-info":[{"award-number":["203738"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["102215"],"award-info":[{"award-number":["102215"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT &gt;40 U\/l; AST &gt;40 U\/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Results:<\/ns4:bold>\n                    All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT &gt;40U\/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Conclusions:<\/ns4:bold>\n                    We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health.\n                  <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.14974.2","type":"journal-article","created":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T09:45:09Z","timestamp":1568886309000},"page":"166","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Metabolic profiling of adolescent non-alcoholic fatty liver disease"],"prefix":"10.12688","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4932-1588","authenticated-orcid":false,"given":"April","family":"Hartley","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8923-0117","authenticated-orcid":false,"given":"Diana L.","family":"Santos Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma L.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6793-2262","authenticated-orcid":false,"given":"Debbie A.","family":"Lawlor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2019,9,19]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"305-12","DOI":"10.1016\/j.jadohealth.2012.01.010","article-title":"Nonalcoholic fatty liver in children and adolescents: an overview.","volume":"51","author":"C Della Corte","year":"2012","journal-title":"J Adolesc Health."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"e0140908","DOI":"10.1371\/journal.pone.0140908","article-title":"The Prevalence of Non-Alcoholic Fatty Liver Disease in Children and 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Hartley","year":"2018","journal-title":"OSF."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-166\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-166\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-166\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T03:55:41Z","timestamp":1611201341000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-166\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,19]]},"references-count":50,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.14974.2","relation":{"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.16921.r36509","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,19]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-166\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.16333.r34501, Warwick B. Dunn, School of Biosciences, University of Birmingham, Birmingham, UK, 07 Jan 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-166\/v1#referee-response-34501","order":0,"name":"referee-response-34501","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>April Hartley<\/b>; <i>Posted: 09 Sep 2019<\/i>; We thank Professor Dunn for the detailed review of our manuscript and apologise for the delay in responding to the suggestions to improve the manuscript.We thank Prof. Dunn for the suggestion of constructing the manuscript with a focus on USS steatosis. We agree that clarifying the use of the liver enzymes would be valuable. However, we do not wish to change the focus of the paper to solely the USS outcomes. First, we prefer to maintain all results from our analysis plan in the paper. Second ALT and AST are routinely collected in large population-based studies and elevated ALT is commonly used in epidemiological studies, e.g. to assess prevalence (Anderson <i>et al<\/i>, PLoS One, 2015) or potential risk factors (De Silva <i>et al<\/i>, Diabetes, 2019). Third, as we only observed 25 cases of USS-steatosis in our population and the outcome measure was binary, our confidence intervals were wide for most of the associations with USS, overlapping the null. Presenting the ALT, AST and USS results allows us to contrast the magnitude of effect for the more specific measure (USS) and the less specific biomarkers of NAFLD (ALT, AST). We have revised the discussion to address this.We also agree that exploring UPLC-MS lipidomic data would be an interesting and informative follow-up to the current study. Unfortunately, these data are not currently available in our studies.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-166\/v2#referee-comment-3944","order":1,"name":"referee-comment-3944","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.16333.r34503, Stefan Stender, Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, 14 Jan 2019, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-166\/v1#referee-response-34503","order":2,"name":"referee-response-34503","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>April Hartley<\/b>; <i>Posted: 09 Sep 2019<\/i>; We thank Dr Stender for his suggestions. We have determined the association between the rs738409 C&gt;G SNP (encoding PNPLA3 I148M) in our study population and present and discuss these results in the revised paper. Bearing in mind the same sample sizes for these analyses (794 for USS and 2,242 for ALT\/AST), and that this variant only explains 2.4% of the variance in CT-assessed steatosis (Speliotes <i>et al<\/i>, PLOS Genetics, 2011), we believe our findings support USS as a more specific marker of NAFLD than ALT with little evidence that AST is a marker.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/3-166\/v2#referee-comment-3945","order":3,"name":"referee-comment-3945","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This research was specifically funded by the UK Medical Research Council (Grant ref: G0801456). All authors work in a Unit that receives support from the University of Bristol and UK Medical Research Council (Grant ref: MC_UU_12013\/5). AH is funded by the Wellcome Trust (Grant ref: 203738\/Z\/16\/Z). ELA is supported by an MRC Skills Development Fellowship (MR\/P014437\/1), and DAL is a National Institute of Health Research Senior Investigator (NF-SI-0611-10196). The UK Medical Research Council and Wellcome (Grant ref: 102215\/2\/13\/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and April Hartley and Debbie A Lawlor will serve as guarantors for the contents of this paper. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}