{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:24:24Z","timestamp":1792167864169,"version":"4.4.0"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T00:00:00Z","timestamp":1565740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"University of Helsinki\u2019s Doctoral Programme in Clinical Research"},{"name":"Diabetes Research"},{"name":"Finnish Medical"},{"name":"Alfred Kordelin Foundations"},{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The European Federation of Pharmaceutical Industries and Associations Innovative Medicines","award":["115372"],"award-info":[{"award-number":["115372"]}]},{"name":"The European Federation of Pharmaceutical Industries and Associations Innovative Medicines","award":["634413"],"award-info":[{"award-number":["634413"]}]},{"name":"Sigrid Juselius Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Abnormal glucose metabolism and nonalcoholic fatty liver disease (NAFLD) are common in patients with human immunodeficiency virus (HIV+ patients), but longitudinal data are lacking. We determined the natural course of NAFLD (liver fat [LFAT]) and type 2 diabetes mellitus (T2DM) in HIV+ patients with and without lipodystrophy (LD+ and LD\u2013, respectively) during a 16-year longitudinal study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>LFAT (by proton magnetic resonance spectroscopy) and clinical characteristics were measured in 41 HIV+ patients at baseline and after 16 years. Liver fibrosis was estimated by measuring liver stiffness using transient elastography (TE) and magnetic resonance elastography (MRE) at 16 years. We also longitudinally studied 28 healthy subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During follow-up, the HIV+ patients gained more body fat (8.6% \u00b1 0.7%) than the control patients (4.5% \u00b1 0.6%, P &amp;lt; .001). Features of insulin resistance increased significantly in the HIV+ patients but not the control patients. A significant proportion (20%, P &amp;lt; .01 vs 0% at baseline) of the HIV+ but none of the control patients developed T2DM. LFAT was significantly higher at baseline in the LD+ (4.3 [1.9\u201311.8]) than the LD\u2013 (1.0 [0.5\u20131.5]; P &amp;lt; .001) HIV+ patients. LFAT remained stable during follow-up in all groups. At follow-up, liver stiffness measured with TE was similar among all HIV, LD+, LD\u2013, and control patients and between the LD+ and LD\u2013 patients measured with MRE. Advanced fibrosis by MRE was observed in 3 of LD+ and none of LD\u2013 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>During 16 years of follow-up, progression of NAFLD is rare compared to development of T2DM in HIV+ patients.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciz435","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T19:11:31Z","timestamp":1558725091000},"page":"1708-1716","source":"Crossref","is-referenced-by-count":11,"title":["Natural Course of Nonalcoholic Fatty Liver Disease and Type 2 Diabetes in Patients With Human Immunodeficiency Virus With and Without Combination Antiretroviral Therapy\u2013associated Lipodystrophy: A 16-Year Follow-up Study"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9775-6669","authenticated-orcid":false,"given":"Susanna","family":"Lallukka-Br\u00fcck","sequence":"first","affiliation":[{"name":"Minerva Foundation Institute for Medical Research"},{"name":"Department of Medicine, University of Helsinki, and Helsinki University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Isokuortti","sequence":"first","affiliation":[{"name":"Minerva Foundation Institute for Medical Research"},{"name":"Department of Medicine, University of Helsinki, and Helsinki University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panu K","family":"Luukkonen","sequence":"first","affiliation":[{"name":"Minerva Foundation Institute for Medical Research"},{"name":"Department of Medicine, University of Helsinki, and Helsinki University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Hakkarainen","sequence":"first","affiliation":[{"name":"Helsinki University Hospital Medical Imaging Center, Helsinki University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Lundbom","sequence":"first","affiliation":[{"name":"Helsinki University Hospital Medical Imaging Center, Helsinki University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jussi","family":"Sutinen","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, University of Helsinki, and Helsinki University Hospital, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannele","family":"Yki-J\u00e4rvinen","sequence":"first","affiliation":[{"name":"Minerva Foundation Institute for Medical Research"},{"name":"Department of Medicine, University of Helsinki, and Helsinki University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,14]]},"reference":[{"key":"2020041000553230700_CIT0001","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1097\/QAD.0000000000001525","article-title":"Fatty liver disease in HIV: common, underappreciated, and understudied","volume":"31","author":"Morse","year":"2017","journal-title":"AIDS"},{"key":"2020041000553230700_CIT0002","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of non-alcoholic fatty liver disease\u2014meta-analytic assessment of prevalence, incidence and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"2020041000553230700_CIT0003","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1097\/QAD.0000000000001504","article-title":"Prevalence and risk factors of nonalcoholic fatty liver disease in HIV-monoinfection","volume":"31","author":"Maurice","year":"2017","journal-title":"AIDS"},{"key":"2020041000553230700_CIT0004","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1038\/ajg.2014.32","article-title":"Risk factors for fatty liver in the multicenter AIDS Cohort study","volume":"109","author":"Price","year":"2014","journal-title":"Am J Gastroenterol"},{"key":"2020041000553230700_CIT0005","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1097\/00001432-200502000-00005","article-title":"Interventions for managing antiretroviral therapy-associated lipoatrophy","volume":"18","author":"Sutinen","year":"2005","journal-title":"Curr Opin Infect Dis"},{"key":"2020041000553230700_CIT0006","doi-asserted-by":"crossref","first-page":"R185","DOI":"10.1530\/EJE-13-0967","article-title":"Metabolic and body composition effects of newer antiretrovirals in HIV-infected patients","volume":"170","author":"Srinivasa","year":"2014","journal-title":"Eur J Endocrinol"},{"key":"2020041000553230700_CIT0007","year":"2017"},{"key":"2020041000553230700_CIT0008","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1097\/00002030-200211080-00011","article-title":"Increased fat accumulation in the liver in HIV-infected patients with antiretroviral therapy-associated lipodystrophy","volume":"16","author":"Sutinen","year":"2002","journal-title":"AIDS"},{"key":"2020041000553230700_CIT0009","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/j.cgh.2018.05.059","article-title":"Magnetic resonance vs transient elastography analysis of patients with nonalcoholic fatty liver disease: a systematic review and pooled analysis of individual participants","volume":"17","author":"Hsu","year":"2019","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2020041000553230700_CIT0010","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1177\/135965350300800303","article-title":"Rosiglitazone in the treatment of HAART-associated lipodystrophy","volume":"8","author":"Sutinen","year":"2003","journal-title":"Antivir Ther"},{"key":"2020041000553230700_CIT0011","doi-asserted-by":"crossref","first-page":"14561","DOI":"10.1038\/s41598-017-14706-0","article-title":"Predictors of liver fat and stiffness in non-alcoholic fatty liver disease (NAFLD)","volume":"7","author":"Lallukka","year":"2017","journal-title":"Sci Rep"},{"key":"2020041000553230700_CIT0012","doi-asserted-by":"crossref","first-page":"E462","DOI":"10.1152\/ajpendo.00064.2004","article-title":"Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population","volume":"288","author":"Szczepaniak","year":"2005","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2020041000553230700_CIT0013","doi-asserted-by":"crossref","first-page":"1862","DOI":"10.1038\/ajg.2012.331","article-title":"Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease","volume":"107","author":"Wong","year":"2012","journal-title":"Am J Gastroenterol"},{"key":"2020041000553230700_CIT0014","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"2020041000553230700_CIT0015","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1097\/QAD.0b013e32833ac7a2","article-title":"Regional adipose tissue measured by MRI over 5 years in HIV-infected and control participants indicates persistence of HIV-associated lipoatrophy","volume":"24","author":"Grunfeld","year":"2010","journal-title":"AIDS"},{"key":"2020041000553230700_CIT0016","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/EDE.0000000000000815","article-title":"Incidence and risk factors for prediabetes and diabetes mellitus among HIV-infected adults on antiretroviral therapy: a systematic review and meta-analysis","volume":"29","author":"Nansseu","year":"2018","journal-title":"Epidemiology"},{"key":"2020041000553230700_CIT0017","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.2337\/dc07-2013","article-title":"Incidence and risk factors for new-onset diabetes in HIV-infected patients: the data collection on adverse events of anti-HIV drugs (D:A:D) study","volume":"31","author":"De Wit","year":"2008","journal-title":"Diabetes Care"},{"key":"2020041000553230700_CIT0018","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s11904-016-0330-z","article-title":"Metabolic complications and glucose metabolism in HIV infection: a review of the evidence","volume":"13","author":"Willig","year":"2016","journal-title":"Curr HIV\/AIDS Rep"},{"key":"2020041000553230700_CIT0019","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1210\/jc.2007-0482","article-title":"Liver fat in the metabolic syndrome","volume":"92","author":"Kotronen","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"2020041000553230700_CIT0020","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1002\/hep.21327","article-title":"Long-term follow-up of patients with NAFLD and elevated liver enzymes","volume":"44","author":"Ekstedt","year":"2006","journal-title":"Hepatology"},{"key":"2020041000553230700_CIT0021","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/ajg.2009.587","article-title":"Predicting fibrosis worsening in obese patients with NASH through parenchymal fibronectin, HOMA-IR, and hypertension","volume":"105","author":"Sorrentino","year":"2010","journal-title":"Am J Gastroenterol"},{"key":"2020041000553230700_CIT0022","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.cgh.2014.04.014","article-title":"Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies","volume":"13","author":"Singh","year":"2015","journal-title":"Clin Gastroenterol Hepatol"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciz435\/29187298\/ciz435.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/70\/8\/1708\/33031783\/ciz435.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/cid\/article-pdf\/70\/8\/1708\/33031783\/ciz435.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T16:33:11Z","timestamp":1663518791000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/70\/8\/1708\/5498863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,14]]},"references-count":22,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2019,8,14]]},"published-print":{"date-parts":[[2020,4,10]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciz435","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,4,15]]},"published":{"date-parts":[[2019,8,14]]}}}