{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:04:01Z","timestamp":1784203441054,"version":"3.55.0"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"\n Background<\/jats:title>\n Drug-induced liver injury (DILI) is a common complication of anti-tuberculosis therapy and frequently leads to treatment interruption or modification. In routine clinical practice, liver function abnormalities during tuberculosis treatment are often attributed to DILI. However, isolated indirect hyperbilirubinemia in the presence of persistently normal transaminase levels represents an atypical biochemical pattern that is inconsistent with classical hepatocellular injury and may indicate alternative underlying conditions, posing a diagnostic challenge in tuberculosis management.<\/jats:p>\n <\/jats:sec>\n \n Case presentation<\/jats:title>\n We report the case of a 22-year-old Han Chinese woman treated for smear-negative pulmonary tuberculosis who developed recurrent elevations in total and indirect bilirubin while alanine aminotransferase and aspartate aminotransferase levels remained persistently within normal ranges. These abnormalities were repeatedly misinterpreted as suspected DILI, resulting in multiple interruptions and modifications of anti-tuberculosis regimens. Bilirubin levels continued to fluctuate despite drug withdrawal, suggesting a non-hepatocellular etiology. Repeated treatment interruption contributed to a delay in effective tuberculosis management exceeding 1 year and was associated with radiological disease progression and cavity formation.<\/jats:p>\n <\/jats:sec>\n \n Management and outcome<\/jats:title>\n \n Further evaluation, including\n UGT1A1<\/jats:italic>\n genetic testing, identified heterozygous promoter (c.-41_-40dupTA) and coding (c.211G&gt;A, p.Gly71Arg) variants, confirming a diagnosis of Gilbert syndrome. Recognition of this underlying condition prevented further unnecessary cessation of anti-tuberculosis therapy. The patient subsequently resumed an individualized regimen guided by drug susceptibility testing and demonstrated radiological improvement during follow-up.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n This case highlights an important diagnostic pitfall during tuberculosis treatment. Persistent indirect hyperbilirubinemia with normal transaminases should prompt consideration of Gilbert syndrome rather than DILI. Early recognition and appropriate genetic testing may prevent unwarranted treatment interruption, reduce the risk of disease progression, and improve treatment continuity. To our knowledge, reports describing Gilbert syndrome masquerading as recurrent suspected DILI during tuberculosis treatment remain exceedingly rare.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmed.2026.1903970","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:10:20Z","timestamp":1784200220000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Persistent indirect hyperbilirubinemia caused by Gilbert syndrome misdiagnosed as drug-induced liver injury during tuberculosis treatment"],"prefix":"10.3389","volume":"13","author":[{"given":"Ping","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Harbin Chest Hospital of Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Operating Room, Harbin Chest Hospital of Harbin Medical University","place":["Harbin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"B1","volume-title":"Global Tuberculosis Report 2024","year":"2024"},{"key":"B2","doi-asserted-by":"publisher","first-page":"101976","DOI":"10.1016\/j.toxrep.2025.101976","article-title":"Insights into medication-induced liver injury: Understanding and management strategies","volume":"14","author":"Tiwari","year":"2025","journal-title":"Toxicol Rep."},{"key":"B3","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1164\/rccm.200510-1666ST","article-title":"An official ATS statement: hepatotoxicity of antituberculosis therapy","volume":"174","author":"Saukkonen","year":"2006","journal-title":"Am J Respir Crit Care Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1016\/j.jhep.2019.02.014","article-title":"EASL clinical practice guidelines: drug-induced liver injury","volume":"70","author":"Andrade","year":"2019","journal-title":"J Hepatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00431-011-1641-0","article-title":"Eponym: Gilbert syndrome","volume":"171","author":"Fretzayas","year":"2012","journal-title":"Eur J Pediatr."},{"key":"B6","volume-title":"Gilbert Syndrome","author":"Grant","year":"2024"},{"key":"B7","first-page":"281","article-title":"A case of drug-resistant pulmonary tuberculosis complicated with chronic myeloid leukemia and Gilbert syndrome","volume":"46","author":"Hu","year":"2023","journal-title":"Zhonghua Jie He He Hu Xi Za Zhi."},{"key":"B8","volume-title":"Treatment of a case of Gilbert syndrome complicated with pulmonary thromboembolism. Proceedings of the 18th National Conference on Respiratory Diseases of the Chinese Medical Association (CTS 2017).","author":"He","year":"2017"},{"key":"B9","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.pedneo.2015.08.008","article-title":"Zheng X-b, Lin M, Zhan X-F, et al. Clinical significance of UGT1A1 genetic analysis in Chinese neonates with severe hyperbilirubinemia","volume":"57","author":"Yang","year":"2016","journal-title":"Pediatr Neonatol"},{"key":"B10","first-page":"59","article-title":"Diagnostic criteria for pulmonary tuberculosis (WS 288-2017)","volume":"3","year":"2018","journal-title":"Electronic J Emerg Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.jceh.2021.01.006","article-title":"Gilbert's syndrome, bilirubin level and UGT1A1*28 genotype in men of north-west region of Russia","volume":"11","author":"Ivanov","year":"2021","journal-title":"J Clin Exp Hepatol."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD009593.pub2","article-title":"Xpert\u00ae MTB\/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults","author":"Steingart","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"B13","doi-asserted-by":"publisher","first-page":"903","DOI":"10.7150\/ijms.101219","article-title":"Understanding genetic screening: harnessing health information to prevent disease risks","volume":"22","author":"Lee","year":"2025","journal-title":"Int J Med Sci."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1903970\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:10:32Z","timestamp":1784200232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1903970\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":13,"alternative-id":["10.3389\/fmed.2026.1903970"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1903970","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]},"article-number":"1903970"}}