{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:53:07Z","timestamp":1774277587385,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) inhibitors are integral in the treatment of immune\u2010mediated inflammatory diseases but may precipitate hepatitis B virus reactivation (HBVr) in HBsAg\u2212\/anti\u2010HBc+ patients. APASL guidance presumes a greater risk with higher\u2010potency agents, but the evidence is limited and conflicting. We conducted a systematic review and meta\u2010analysis to assess whether TNF\u2010\u03b1 inhibitor potency alters HBVr risk in HBsAg\u2212\/anti\u2010HBc+ individuals and to identify predictors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched on May 29, 2025. Eligible cohort studies and randomised trials reported HBVr under TNF\u2010\u03b1 inhibitor treatment in HBsAg\u2212\/anti\u2010HBc+ patients. The risk of bias was assessed via the Newcastle\u2010Ottawa Scale and the RoB 2.0. Random\u2010effects meta\u2010analysis was used to pool the HBV incidence and risk ratios (RRs), and subgroup analyses were used to explore heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirteen cohorts (1492 patients) reported 37 HBVr events, yielding a pooled incidence of 2.3% (95% CI 1.1%\u20134.8%;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200956%). The incidence was 3.9% (95%\u2009CI\u20092.1%\u20137.0%;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200934%) with high\u2010potency agents and 3.6% (95%\u2009CI\u20092.2%\u20135.8%;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%) with low\u2010potency agents. High\u2010 and low\u2010potency TNF\u2010\u03b1 inhibitors were associated with comparable HBVr risk (RR 0.92, 95% CI\u20090.47\u20131.79;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%). Agent\u2010specific incidences ranged from 3.6% to 5.4%, without significant differences compared with etanercept. Anti\u2010HBs seronegativity conferred a greater risk (incidence, 8.2% vs. 3.1%; RR 2.77, 95% CI 1.42\u20135.39). The reactivation risk did not vary by geography, age, indication, follow\u2010up, design, or bias rating.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In HBsAg\u2212\/anti\u2010HBc+ patients, TNF\u2010\u03b1 inhibitor potency did not significantly alter the already low risk of HBVr. Continued surveillance is warranted, particularly in anti\u2010HBs\u2010negative individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>INPLASY202570100<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70532","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T10:08:31Z","timestamp":1770026911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TNF\u2010\u03b1 Inhibitors and HBV Reactivation Risk in HBsAg\u2212\/Anti\u2010HBc+ Patients: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1111","volume":"46","author":[{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen\u2010Chou","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation  Chia\u2010Yi Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-022-05136-x"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2017.12.025"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15793"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030275"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2017.11.005"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14712598.2017.1340453"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keu172"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-021-10239-x"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13401"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.5152\/tjg.2018.18032"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2018.04.033"},{"issue":"1","key":"e_1_2_12_13_1","first-page":"93","article-title":"Long\u2010Term Safety of Anti\u2010TNF Agents on the Liver of Patients With Spondyloarthritis and Potential Occult Hepatitis B Viral Infection: An Observational Multicentre Study","volume":"35","author":"Giannitti C.","year":"2017","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27716"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-013-2385-1"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2013.11.014"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/s10165-011-0458-z"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2010.148783"},{"issue":"2","key":"e_1_2_12_19_1","first-page":"285","article-title":"Anti\u2010Tumor Necrosis Factor Treatment in Occult Hepatitis B Virus Infection: A Retrospective Analysis of 62 Patients With Psoriatic Disease","volume":"25","author":"Cassano N.","year":"2011","journal-title":"Journal of Biological Regulators and Homeostatic Agents"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20130"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2868"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.70152"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.07.003"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15959"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2024.11.008"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2022-002726"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-220774"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-023-08141-7"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59406-4"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70532","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.70532","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70532","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T13:56:14Z","timestamp":1774274174000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70532"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,2]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/liv.70532"],"URL":"https:\/\/doi.org\/10.1111\/liv.70532","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,2]]},"assertion":[{"value":"2025-11-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70532"}}