{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T20:28:20Z","timestamp":1790800100398,"version":"4.1.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Poor adherence to medication can lead to treatment failure in healthcare workers (HWCs) with latent tuberculosis infection (LTBI) who are at high risk of developing active tuberculosis. However, the factors associated with non-completion of nine-month LTBI treatment with isoniazid (9\u2009H) have not been well studied. We investigated the completion rate and factors affecting adherence to LTBI treatment with 9\u2009H among HCWs. A prospective cohort study of 114 HCWs who were diagnosed with LTBI by QuantiFERON-TB Gold In-Tube tests were performed in a single university hospital between June 2016 and December 2017. All patients received the 9\u2009H LTBI treatment. At each visit, treatment adherence and development of adverse reactions to isoniazid were evaluated via a standard questionnaire. To evaluate the impact of the severity of hepatotoxicity on non-completion of LTBI treatment, we classified hepatotoxicity into two groups: severe hepatotoxicity was defined as alanine aminotransferase &gt;3.0 times the upper normal limit (UNL) with symptoms or \u2009=\u20095.0 times the UNL. Mild hepatotoxicity was defined as alanine aminotransferase&gt;UNL, but not meet the definition of severe hepatotoxicity. Overall, 71 HCWs (62.3%) completed LTBI treatment with 9\u2009H while 43 HCWs (37.7%) discontinued their treatment. Most discontinuation (81.4%, 35\/43) occurred during the first three months of treatment. There were no significant differences in age, sex, occupation, or comorbidities between the HCWs who completed and those who discontinued LTBI treatment. However, HCWs who discontinued LTBI treatment had more hepatotoxicity than those who completed treatment (44.2% vs. 11.3%, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Cox proportional hazard analysis revealed that hepatotoxicity is the only factor significantly associated with discontinuation of 9\u2009H LTBI treatment (unadjusted HR\u2009=\u20092.89, 95% CI\u2009=\u20091.62\u20135.46). In multivariable analysis, not only severe hepatotoxicity (adjusted HR\u2009=\u20097.99, 95% CI\u2009=\u20093.05\u201320.94) but also mild hepatotoxicity was significantly associated with discontinuation of LTBI treatment (adjusted HR\u2009=\u20092.34, 95% CI\u2009=\u20091.05\u20135.21). The completion rate of 9\u2009H LTBI treatment was 62.3% among HCWs. While age, sex, occupation, and pretreatment comorbidities were not associated with treatment completion, isoniazid-induced hepatotoxicity significantly affected adherence.<\/jats:p>","DOI":"10.1038\/s41598-020-63156-8","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T10:03:27Z","timestamp":1586945007000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Adherence to nine-month isoniazid for latent tuberculosis infection in healthcare workers: a prospective study in a tertiary hospital"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8636-446X","authenticated-orcid":false,"given":"Sung Jun","family":"Chung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gun Woo","family":"Koo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hee","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoomi","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Won","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai Sun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yong","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Heon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7132-2988","authenticated-orcid":false,"given":"Jang Won","family":"Sohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Joo","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"key":"63156_CR1","doi-asserted-by":"publisher","first-page":"488","DOI":"10.3201\/eid1703.100947","volume":"17","author":"I Baussano","year":"2011","unstructured":"Baussano, I. et al. Tuberculosis among health care workers. Emerging infectious diseases 17, 488\u2013494 (2011).","journal-title":"Emerging infectious diseases"},{"key":"63156_CR2","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1056\/NEJM199501123320206","volume":"332","author":"D Menzies","year":"1995","unstructured":"Menzies, D., Fanning, A., Yuan, L. & Fitzgerald, M. Tuberculosis among health care workers. The New England journal of medicine 332, 92\u201398 (1995).","journal-title":"The New England journal of medicine"},{"key":"63156_CR3","doi-asserted-by":"publisher","first-page":"274","DOI":"10.4046\/trd.2018.0020","volume":"81","author":"JS Park","year":"2018","unstructured":"Park, J. S. The Prevalence and Risk Factors of Latent Tuberculosis Infection among Health Care Workers Working in a Tertiary Hospital in South Korea. Tuberculosis and respiratory diseases 81, 274\u2013280 (2018).","journal-title":"Tuberculosis and respiratory diseases"},{"key":"63156_CR4","first-page":"593","volume":"11","author":"D Menzies","year":"2007","unstructured":"Menzies, D., Joshi, R. & Pai, M. Risk of tuberculosis infection and disease associated with work in health care settings. The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 11, 593\u2013605 (2007).","journal-title":"The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease"},{"key":"63156_CR5","doi-asserted-by":"publisher","first-page":"e0164034","DOI":"10.1371\/journal.pone.0164034","volume":"11","author":"S Nasreen","year":"2016","unstructured":"Nasreen, S., Shokoohi, M. & Malvankar-Mehta, M. S. Prevalence of Latent Tuberculosis among Health Care Workers in High Burden Countries: A Systematic Review and Meta-Analysis. PloS one 11, e0164034 (2016).","journal-title":"PloS one"},{"key":"63156_CR6","first-page":"348","volume":"11","author":"K Cho","year":"2018","unstructured":"Cho, K. et al. Prevalence of latent tuberculosis infection at congregated settings in the Republic of Korea, 2017. J Public Health Wkly Rep 11, 348\u2013354 (2018).","journal-title":"J Public Health Wkly Rep"},{"key":"63156_CR7","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.5588\/ijtld.18.0047","volume":"22","author":"S Kim","year":"2018","unstructured":"Kim, S., Choi, H., Jang, Y. J., Park, S. H. & Lee, H. Prevalence of and factors related to latent tuberculous infection among all employees in a referral hospital. The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 22, 1329\u20131335 (2018).","journal-title":"The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease"},{"key":"63156_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-37319-7","volume":"9","author":"H Lee","year":"2019","unstructured":"Lee, H. et al. Factors associated with non-initiation of latent tuberculosis treatment among healthcare workers with a positive interferon-gamma releasing assay. Scientific reports 9, 61 (2019).","journal-title":"Scientific reports"},{"key":"63156_CR9","doi-asserted-by":"publisher","first-page":"689","DOI":"10.7326\/0003-4819-149-10-200811180-00003","volume":"149","author":"D Menzies","year":"2008","unstructured":"Menzies, D. et al. Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial. Annals of internal medicine 149, 689\u2013697 (2008).","journal-title":"Annals of internal medicine"},{"key":"63156_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-12-468","volume":"12","author":"ND Goswami","year":"2012","unstructured":"Goswami, N. D. et al. Predictors of latent tuberculosis treatment initiation and completion at a U.S. public health clinic: a prospective cohort study. BMC public health 12, 468 (2012).","journal-title":"BMC public health"},{"key":"63156_CR11","doi-asserted-by":"publisher","first-page":"e292","DOI":"10.1016\/j.ijid.2009.05.007","volume":"14","author":"J Li","year":"2010","unstructured":"Li, J., Munsiff, S. S., Tarantino, T. & Dorsinville, M. Adherence to treatment of latent tuberculosis infection in a clinical population in New York City. International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases 14, e292\u2013297 (2010).","journal-title":"International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases"},{"key":"63156_CR12","doi-asserted-by":"publisher","first-page":"903","DOI":"10.5588\/ijtld.12.0677","volume":"17","author":"LR Codecasa","year":"2013","unstructured":"Codecasa, L. R. et al. Isoniazid preventive treatment: predictors of adverse events and treatment completion. The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 17, 903\u2013908 (2013).","journal-title":"The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease"},{"key":"63156_CR13","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1056\/NEJMoa1714283","volume":"379","author":"D Menzies","year":"2018","unstructured":"Menzies, D. et al. Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults. The New England journal of medicine 379, 440\u2013453 (2018).","journal-title":"The New England journal of medicine"},{"key":"63156_CR14","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.jinf.2013.07.015","volume":"67","author":"AC Pettit","year":"2013","unstructured":"Pettit, A. C., Bethel, J., Hirsch-Moverman, Y., Colson, P. W. & Sterling, T. R. Female sex and discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis. The Journal of infection 67, 424\u2013432 (2013).","journal-title":"The Journal of infection"},{"key":"63156_CR15","first-page":"551","volume":"14","author":"A Trajman","year":"2010","unstructured":"Trajman, A. et al. Factors associated with treatment adherence in a randomised trial of latent tuberculosis infection treatment. The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 14, 551\u2013559 (2010).","journal-title":"The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease"},{"key":"63156_CR16","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.5588\/ijtld.18.0280","volume":"22","author":"EH Lee","year":"2018","unstructured":"Lee, E. H. et al. Treatment of latent tuberculous infection among health care workers at a tertiary hospital in Korea. The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 22, 1336\u20131343 (2018).","journal-title":"The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease"},{"key":"63156_CR17","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1086\/674855","volume":"35","author":"HH Balkhy","year":"2014","unstructured":"Balkhy, H. H. et al. Compliance with postexposure screening and treatment of latent tuberculosis infection among healthcare workers in a tertiary care hospital in Saudi Arabia. Infection control and hospital epidemiology 35, 176\u2013181 (2014).","journal-title":"Infection control and hospital epidemiology"},{"key":"63156_CR18","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1378\/chest.122.5.1609","volume":"122","author":"SJ Shukla","year":"2002","unstructured":"Shukla, S. J., Warren, D. K., Woeltje, K. F., Gruber, C. A. & Fraser, V. J. Factors associated with the treatment of latent tuberculosis infection among health-care workers at a midwestern teaching hospital. Chest 122, 1609\u20131614 (2002).","journal-title":"Chest"},{"key":"63156_CR19","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1093\/cid\/cix725","volume":"65","author":"E Arguello Perez","year":"2017","unstructured":"Arguello Perez, E., Seo, S. K., Schneider, W. J., Eisenstein, C. & Brown, A. E. Management of Latent Tuberculosis Infection Among Healthcare Workers: 10-Year Experience at a Single Center. Clin Infect Dis 65, 2105\u20132111 (2017).","journal-title":"Clin Infect Dis"},{"key":"63156_CR20","unstructured":"WHO. Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. World Health Organization (2018)."},{"key":"63156_CR21","doi-asserted-by":"crossref","unstructured":"Targeted tuberculin testing and treatment of latent tuberculosis infection. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999. This is a Joint Statement of the American Thoracic Society (ATS) and the Centers for Disease Control and Prevention (CDC). This statement was endorsed by the Council of the Infectious Diseases Society of America. (IDSA), September 1999, and the sections of this statement. American journal of respiratory and critical care medicine 161, S221-247 (2000).","DOI":"10.1164\/ajrccm.161.supplement_3.ats600"},{"key":"63156_CR22","unstructured":"Joint Committee for the Revision of Korean Guidelines for Tuberculosis, Korean Centers for Disease Control and Prevention. Korean guidelines for tuberculosis. Third edition. (2017)."},{"key":"63156_CR23","doi-asserted-by":"crossref","unstructured":"Saukkonen, J. J. et al. An official ATS statement: hepatotoxicity of antituberculosis therapy. 174, 935-952 (2006).","DOI":"10.1164\/rccm.200510-1666ST"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-63156-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-63156-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-63156-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T09:39:15Z","timestamp":1670319555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-63156-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["63156"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-63156-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,15]]},"assertion":[{"value":"29 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 April 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6462"}}