{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:38:42Z","timestamp":1792017522969,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rheumatoid arthritis (RA) patients seropositive for hepatitis B core antibody (HBcAb) and negative for hepatitis B surface antigen (HBsAg) are at risk of hepatitis B virus (HBV) reactivation when treated with biologic or targeted synthetic (b\/ts) disease\u2010modifying antirheumatic drugs (DMARDs). The study aims to investigate the risk in this population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>From January 2004 through December 2020, 1068 RA patients undergoing b\/tsDMARDs therapy and 416 patients with HBsAg\u2212\/HBcAb+ were enrolled. Factors associated with HBV reactivation were analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During 2845 person\u2010years of follow\u2010up, 27 of 416 (6.5%,9.5 per 1000 person\u2010years) patients developed HBV reactivation, with a cumulative rate of HBV reactivation of 3.5% at 5\u2009years, 6.1% at 10\u2009years and 24.2% at 17\u2009years. The median interval from beginning b\/tsDMARDs to HBV reactivation was 85\u2009months (range: 9\u2013186\u2009months). The risk of HBV reactivation varied by type of b\/tsDMARD, with rituximab having the highest risk (incidence rate: 48.3 per 1000 person\u2010years), followed by abatacept (incidence rate: 24.0 per 1000 person\u2010years). In multivariate analysis, rituximab (adjusted hazard ratio [aHR]: 15.77, 95% confidence interval [CI]: 4.12\u201360.32, <jats:italic>p<\/jats:italic>\u2009=\u2009.001), abatacept (aHR: 9.30, 1.83\u201347.19, <jats:italic>p<\/jats:italic>\u2009=\u2009.007), adalimumab (aHR: 3.86, 1.05\u201314.26, <jats:italic>p<\/jats:italic>\u2009=\u2009.04) and negative baseline HBV surface antibody (anti\u2010HBs, &lt;10\u2009mIU\/mL) (aHR: 3.89, 1.70\u20138.92, <jats:italic>p<\/jats:italic>\u2009&lt;\u2009.001) were independent risk factors for HBV reactivation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>HBsAg\u2212\/HBcAb+ RA patients are susceptible to HBV reactivation during b\/tsDMARD therapy. Those with negative baseline anti\u2010HBs and those on certain b\/tsDMARDs, such as rituximab, abatacept and adalimumab, have high reactivation risks. Risk stratification and management should be based on the patient's baseline anti\u2010HBs titre and type of therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15793","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T01:25:36Z","timestamp":1701134736000},"page":"497-507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["HBV reactivation in HBsAg\u2212\/HBcAb+ rheumatoid arthritis patients receiving biologic\/targeted synthetic DMARDs"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-3104","authenticated-orcid":false,"given":"Meng Hsuan","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Pharmacy Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6951-4646","authenticated-orcid":false,"given":"Chih\u2010Wei","family":"Tseng","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzuchi University  Hualien Taiwan"},{"name":"Division of Gastroenterology, Department of Internal Medicine Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping\u2010Hung","family":"Ko","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzuchi University  Hualien Taiwan"},{"name":"Division of Gastroenterology, Department of Internal Medicine Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sz\u2010Tsan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzuchi University  Hualien Taiwan"},{"name":"Division of Rheumatology, Department of Internal Medicine Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010Chi","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzuchi University  Hualien Taiwan"},{"name":"Division of Rheumatology, Department of Internal Medicine Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien\u2010Hsueh","family":"Tung","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzuchi University  Hualien Taiwan"},{"name":"Division of Rheumatology, Department of Internal Medicine Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-3018","authenticated-orcid":false,"given":"Kuo\u2010Chih","family":"Tseng","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzuchi University  Hualien Taiwan"},{"name":"Division of Gastroenterology, Department of Internal Medicine Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang\u2010Yung","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzuchi University  Hualien Taiwan"},{"name":"Division of Rheumatology, Department of Internal Medicine Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi\u2010Hui","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning\u2010Sheng","family":"Lai","sequence":"additional","affiliation":[{"name":"School of Medicine, Tzuchi University  Hualien Taiwan"},{"name":"Division of Rheumatology, Department of Internal Medicine Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220973"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204223"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2016.09.012"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27609"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2022-002726"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-021-10239-x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29800"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.10.039"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1759720X20912646"},{"issue":"4","key":"e_1_2_13_12_1","first-page":"480","article-title":"Hepatitis B virus reactivation in HBsAg\u2010negative, anti\u2010HBc\u2010positive patients receiving immunosuppressive therapy: a systematic review","volume":"31","author":"Cholongitas E","year":"2018","journal-title":"Ann Gastroenterol"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0196210"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13582"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59406-4"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2017.12.014"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.07.003"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220774"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12080815"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27716"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209973"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.151105"},{"issue":"5","key":"e_1_2_13_24_1","first-page":"831","article-title":"Incidence and clinical characteristics of hepatitis B virus reactivation in HBsAg\u2010negative\/HBcAb\u2010positive patients receiving rituximab for rheumatoid arthritis","volume":"35","author":"Tien YC","year":"2017","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2022.101425"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.12359"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13401"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22786"},{"issue":"1","key":"e_1_2_13_29_1","first-page":"102","article-title":"Liver safety of non\u2010tumour necrosis factor inhibitors in rheumatic patients with past hepatitis B virus infection: an observational, controlled, long\u2010term study","volume":"36","author":"Papalopoulos I","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17155"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.780"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.02.027"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.15793","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T08:17:30Z","timestamp":1719303450000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.15793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,27]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1111\/liv.15793"],"URL":"https:\/\/doi.org\/10.1111\/liv.15793","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,27]]},"assertion":[{"value":"2023-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}