{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:51:41Z","timestamp":1782237101409,"version":"3.54.5"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009898","name":"Beckett-Fonden","doi-asserted-by":"publisher","award":["22-2-9924"],"award-info":[{"award-number":["22-2-9924"]}],"id":[{"id":"10.13039\/501100009898","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Infectious Diseases, Copenhagen University Hospital: Hvidovre, Denmark"},{"DOI":"10.13039\/501100007437","name":"TrygFonden","doi-asserted-by":"publisher","award":["101390 580"],"award-info":[{"award-number":["101390 580"]}],"id":[{"id":"10.13039\/501100007437","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007437","name":"TrygFonden","doi-asserted-by":"publisher","award":["20045"],"award-info":[{"award-number":["20045"]}],"id":[{"id":"10.13039\/501100007437","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background &amp; aims<\/jats:title>\n                    <jats:p>Having both chronic hepatitis B and hepatic steatosis increases the risk of liver-related morbidity and mortality. We aimed to investigate if high-intensity interval training could decrease the liver fat-fraction and improve liver status, body composition, lipid- and glucose metabolism, and blood pressure in patients with chronic hepatitis B and hepatic steatosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a randomised, controlled trial, patients with chronic hepatitis B and hepatic steatosis were randomised 1:1 to high-intensity interval training over 12 weeks or no intervention. The primary outcome was reduction in liver fat-fraction (\u2265 2.8%), assessed by magnetic resonance imaging. Secondary outcomes were body composition, indices of glucose metabolism, blood lipids, blood pressure, alanine aminotransferase, physical fitness assessed by maximal oxygen consumption (VO\n                      <jats:sub>2<\/jats:sub>\n                      max), and self-assessed health. The trial was discontinued before reaching the planned sample size due to slow recruitment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nineteen patients were included, and 14 completed the trial (seven per group). Changes in liver fat-fraction showed a between-group difference of \u22122.03% [95% CI: \u22125.5 to 1.4; p\u2009=\u20090.22]. Exercising patients improved VO\n                      <jats:sub>2<\/jats:sub>\n                      max by 5.6 mL\/kg\/min [1.7 to 9.5; p\u2009&lt;\u20090.05] and emotional well-being by 18.07 points [6.6 to 29.6; p\u2009&lt;\u20090.05]. The exercise intervention did not affect total body fat \u22120.35% [\u22122.8 to 2.1] or lean body mass 0.6 kg [\u22120.7 to 1.9]. Changes in glucose tolerance, insulin secretion, Matsuda index \u22120.89 [\u22122.5 to 0.5; p\u2009=\u20090.18], cholesterol 0.29 mmol\/L [\u22120.3 to 0.9; p\u2009=\u20090.32] and systolic blood pressure 6.36 mmHg [\u22126.4 to 19.1; p\u2009=\u20090.29] did not differ significantly between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We did not observe a significant effect of high-intensity interval training on liver fat-fraction in patients with chronic hepatitis B and hepatic steatosis. Due to premature discontinuation and the resulting limited sample size, the study was underpowered, and the findings should be interpreted as exploratory. Nevertheless, the intervention improved physical fitness and emotional well-being.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0351547","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:32:58Z","timestamp":1782235978000},"page":"e0351547","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of high-intensity interval training in patients with chronic hepatitis B and hepatic steatosis: A randomised controlled trial"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5747-1581","authenticated-orcid":true,"given":"Sofie","family":"Jespersen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmita","family":"Fritt-Rasmussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody Garett","family":"Durrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Fallentin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen Sloth","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Thielsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bandholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sten","family":"Madsbad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bente Klarlund","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5095-0624","authenticated-orcid":true,"given":"Christian","family":"Ritz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3133-2724","authenticated-orcid":true,"given":"Nina","family":"Weis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke","family":"Krogh-Madsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"pone.0351547.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/j.jhep.2016.01.027","article-title":"Overview of hepatitis B viral replication and genetic variability","volume":"64","author":"S Tong","year":"2016","journal-title":"J Hepatol"},{"issue":"4","key":"pone.0351547.ref002","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/j.jhep.2015.01.002","article-title":"Risk of hepatocellular carcinoma in chronic hepatitis B: Assessment and modification with current antiviral therapy","volume":"62","author":"GV Papatheodoridis","year":"2015","journal-title":"J Hepatol"},{"issue":"5","key":"pone.0351547.ref003","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s12072-020-10086-2","article-title":"Hepatitis B virus infection and diabetes mellitus: The Kailuan prospective cohort study in China","volume":"14","author":"S Lei","year":"2020","journal-title":"Hepatol Int"},{"issue":"28","key":"pone.0351547.ref004","doi-asserted-by":"crossref","first-page":"3163","DOI":"10.3748\/wjg.v24.i28.3163","article-title":"Health behaviors of Korean adults with hepatitis B: Findings of the 2016 Korean National Health and Nutrition Examination Survey","volume":"24","author":"Y-H Yi","year":"2018","journal-title":"World J Gastroenterol"},{"issue":"1","key":"pone.0351547.ref005","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1111\/j.1365-2036.2007.03538.x","article-title":"Metabolic syndrome is associated with severe fibrosis in chronic viral hepatitis and non-alcoholic steatohepatitis","volume":"27","author":"E Tsochatzis","year":"2008","journal-title":"Aliment Pharmacol Ther"},{"issue":"23","key":"pone.0351547.ref006","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.21037\/atm-21-3052","article-title":"Concurrence and impact of hepatic steatosis on chronic hepatitis B patients: A systematic review and meta-analysis","volume":"9","author":"D Jiang","year":"2021","journal-title":"Ann Transl Med"},{"issue":"3","key":"pone.0351547.ref007","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1111\/jgh.13536","article-title":"Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B","volume":"32","author":"AWH Chan","year":"2017","journal-title":"J Gastroenterol Hepatol"},{"key":"pone.0351547.ref008","article-title":"EASL clinical practice guidelines on the management of hepatitis B virus infection","author":"Liver European Association for the Study of the","year":"2025","journal-title":"J Hepatol"},{"issue":"4","key":"pone.0351547.ref009","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/13813455.2016.1202985","article-title":"Insulin sensitivity, body composition and adipose depots following 12 w combined endurance and strength training in dysglycemic and normoglycemic sedentary men","volume":"122","author":"TM Langleite","year":"2016","journal-title":"Arch Physiol Biochem"},{"issue":"12","key":"pone.0351547.ref010","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1042\/CS20150308","article-title":"Modified high-intensity interval training reduces liver fat and improves cardiac function in non-alcoholic fatty liver disease: A randomized controlled trial","volume":"129","author":"K Hallsworth","year":"2015","journal-title":"Clin Sci (Lond)"},{"issue":"16","key":"pone.0351547.ref011","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.4254\/wjh.v7.i16.2041","article-title":"Physical activity as a treatment of non-alcoholic fatty liver disease: A systematic review","volume":"7","author":"M Whitsett","year":"2015","journal-title":"World J Hepatol"},{"issue":"1","key":"pone.0351547.ref012","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1186\/s13063-023-07385-y","article-title":"Effect of aerobic exercise training on the fat fraction of the liver in persons with chronic hepatitis B and hepatic steatosis: Trial protocol for a randomized controlled intervention trial- The FitLiver study","volume":"24","author":"S Jespersen","year":"2023","journal-title":"Trials"},{"issue":"6","key":"pone.0351547.ref013","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1007\/s00125-016-3902-y","article-title":"EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease","volume":"59","author":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO)","year":"2016","journal-title":"Diabetologia"},{"issue":"1","key":"pone.0351547.ref014","doi-asserted-by":"crossref","first-page":"101133","DOI":"10.1016\/j.aohep.2023.101133","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"29","author":"ME Rinella","year":"2024","journal-title":"Ann Hepatol"},{"issue":"4","key":"pone.0351547.ref015","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1007\/s00330-024-11001-1","article-title":"Evaluation of MRI proton density fat fraction in hepatic steatosis: A systematic review and meta-analysis","volume":"35","author":"N Azizi","year":"2025","journal-title":"Eur Radiol"},{"issue":"9","key":"pone.0351547.ref016","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp","volume":"22","author":"M Matsuda","year":"1999","journal-title":"Diabetes Care"},{"issue":"2","key":"pone.0351547.ref017","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1152\/japplphysiol.00078.2023","article-title":"Impact of high-intensity interval training on cardiac structure and function after COVID-19: An investigator-blinded randomized controlled trial","volume":"135","author":"IE Rasmussen","year":"2023","journal-title":"J Appl Physiol (1985)"},{"key":"pone.0351547.ref018","author":"SN Thomsen","year":"2023"},{"issue":"5","key":"pone.0351547.ref019","first-page":"377","article-title":"Psychophysical bases of perceived exertion","volume":"14","author":"GA Borg","year":"1982","journal-title":"Med Sci Sports Exerc"},{"key":"pone.0351547.ref020","author":"JC Br\u00f8nd"},{"issue":"11","key":"pone.0351547.ref021","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/S0895-4356(98)00091-2","article-title":"The danish SF-36 health survey: Translation and preliminary validity studies","volume":"51","author":"JB Bjorner","year":"1998","journal-title":"J Clin Epidemiol"},{"issue":"6","key":"pone.0351547.ref022","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/00005650-199206000-00002","article-title":"The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection","volume":"30","author":"JE Ware","year":"1992","journal-title":"Med Care"},{"issue":"6846","key":"pone.0351547.ref023","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1136\/bmj.305.6846.160","article-title":"Validating the SF-36 health survey questionnaire: New outcome measure for primary care","volume":"305","author":"JE Brazier","year":"1992","journal-title":"BMJ"},{"issue":"12","key":"pone.0351547.ref024","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1007\/s00296-016-3567-3","article-title":"Validity and reliability of the Short Form 36 Health Surveys (SF-36) among patients with spondyloarthritis in Singapore","volume":"36","author":"YH Kwan","year":"2016","journal-title":"Rheumatol Int"},{"issue":"24","key":"pone.0351547.ref025","article-title":"Reliability, validity, and sensitivity of short-form 36 health survey (SF-36) in patients with sick sinus syndrome","volume":"102","author":"Q Wu","year":"2023","journal-title":"Med"},{"key":"pone.0351547.ref026","year":"1995"},{"issue":"1","key":"pone.0351547.ref027","doi-asserted-by":"crossref","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting linear mixed-effects models using lme4","volume":"67","author":"D Bates","year":"2015","journal-title":"J Stat Softw"},{"issue":"11","key":"pone.0351547.ref028","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1002\/oby.23887","article-title":"Effects of short-term supervised exercise training on liver fat in adolescents with obesity: A randomized controlled trial","volume":"31","author":"E Tas","year":"2023","journal-title":"Obesity (Silver Spring)"},{"issue":"8","key":"pone.0351547.ref029","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1111\/apt.15989","article-title":"Improvement in histological endpoints of MAFLD following a 12-week aerobic exercise intervention","volume":"52","author":"P O\u2019Gorman","year":"2020","journal-title":"Aliment Pharmacol Ther"},{"issue":"08","key":"pone.0351547.ref030","article-title":"A pilot randomised study of the metabolic and histological effects of exercise in non-alcoholic steatohepatitis","volume":"04","author":"IJH Nuala M Byrne","year":"2013","journal-title":"J Diabetes Metab"},{"issue":"1","key":"pone.0351547.ref031","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/hep.26343","article-title":"Liver stiffness is influenced by a standardized meal in patients with chronic hepatitis C virus at different stages of fibrotic evolution","volume":"58","author":"U Arena","year":"2013","journal-title":"Hepatology"},{"issue":"4","key":"pone.0351547.ref032","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1128\/JVI.02604-15","article-title":"Hepatitis B Virus X Protein Induces Hepatic Steatosis by enhancing the expression of liver fatty acid binding protein","volume":"90","author":"YL Wu","year":"2016","journal-title":"J Virol"},{"issue":"1","key":"pone.0351547.ref033","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1007\/s11886-025-02289-6","article-title":"VO2 Max in clinical cardiology: Clinical applications, evidence gaps, and future directions","volume":"27","author":"HM Abdalla","year":"2025","journal-title":"Current Cardiovascular Reports"},{"issue":"9","key":"pone.0351547.ref034","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1136\/gut.2008.151977","article-title":"High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease","volume":"58","author":"K Kantartzis","year":"2009","journal-title":"Gut"},{"issue":"2","key":"pone.0351547.ref035","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.rmed.2009.09.006","article-title":"The SF-36 and SGRQ: Validity and first look at minimum important differences in IPF","volume":"104","author":"JJ Swigris","year":"2010","journal-title":"Respir Med"},{"issue":"1","key":"pone.0351547.ref036","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1378\/chest.07-0275","article-title":"Estimating a minimally important difference in pulmonary arterial hypertension following treatment with sildenafil","volume":"135","author":"C Gilbert","year":"2009","journal-title":"Chest"},{"issue":"5","key":"pone.0351547.ref037","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/MLR.000000000000010311","article-title":"Patient-reported functional health and well-being outcomes with drug therapy: A systematic review of randomized trials using the SF-36 health survey","volume":"52","author":"DM Frendl","year":"2014","journal-title":"Med Care"},{"issue":"1","key":"pone.0351547.ref038","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1249\/01.mss.0000180883.32116.28","article-title":"Inverse association between physical inactivity and mental health in men and women","volume":"38","author":"DI Galper","year":"2006","journal-title":"Med Sci Sports Exerc"},{"key":"pone.0351547.ref039","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.b3410","article-title":"Effect of a multimodal high intensity exercise intervention in cancer patients undergoing chemotherapy: Randomised controlled trial","volume":"339","author":"L Adamsen","year":"2009","journal-title":"BMJ"},{"issue":"1","key":"pone.0351547.ref040","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1080\/23744235.2022.2125065","article-title":"Increasing prevalence of chronic hepatitis B virus infection and low linkage to care in Denmark on 31 December 2016 - an update based on nationwide registers","volume":"55","author":"S Bollerup","year":"2023","journal-title":"Infect Dis (Lond)"},{"issue":"2","key":"pone.0351547.ref041","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s10620-020-06224-3","article-title":"Patient knowledge, beliefs and barriers to hepatitis B care: Results of a multicenter, multiethnic patient survey","volume":"66","author":"NA Mukhtar","year":"2021","journal-title":"Dig Dis Sci"},{"issue":"5","key":"pone.0351547.ref042","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.jhep.2016.12.022","article-title":"Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis","volume":"66","author":"T Karlas","year":"2017","journal-title":"J Hepatol"},{"issue":"3","key":"pone.0351547.ref043","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.jhep.2024.04.031","article-title":"EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)","volume":"81","author":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO)","year":"2024","journal-title":"J Hepatol"},{"issue":"23","key":"pone.0351547.ref044","doi-asserted-by":"crossref","first-page":"4870","DOI":"10.3390\/nu15234870","article-title":"Time-restricted fasting improves liver steatosis in non-alcoholic fatty liver disease-a single blinded crossover trial","volume":"15","author":"J Feehan","year":"2023","journal-title":"Nutrients"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0351547","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:33:06Z","timestamp":1782235986000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0351547"}},"subtitle":[],"editor":[{"given":"Sophia Eugenia","family":"Mart\u00ednez-V\u00e1zquez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0351547","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}