{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T18:41:33Z","timestamp":1784832093852,"version":"3.55.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsmedizin Rostock"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pulm Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Liver-related side effects are a known complication of treatment with elexacaftor\/tezacaftor\/ivacaftor (ETI) for cystic fibrosis (CF). Gilbert\u2019s syndrome is caused by a genetic mutation that reduces activity of the enzyme UDP glucuronosyltransferase 1 polypeptide A1 (UGT1A1), causing elevated levels of unconjugated bilirubin in the blood and duodenal bile. The presence of Gilbert\u2019s syndrome and CF might represent additive risk factors for liver-related adverse events during ETI treatment. This case series describes six people with CF (pwCF) in whom previously unknown Gilbert\u2019s syndrome was unmasked after initiation of treatment with ETI. Although all patients had some level of hepatic dysfunction and\/or elevated levels of bilirubin after initiation of ETI, the clinical course varied. Only one patient had to stop ETI therapy altogether, while the others were able to continue treatment (some at a reduced dosage and others at the full recommended daily dosage). All patients, even those using a lower dosage, experienced clinical benefit during ETI therapy. Gilbert\u2019s syndrome is not a contraindication for ETI therapy but may be mistaken for a risk factor for liver-related adverse events in pwCF. This is something that physicians need to be aware of in pwCF who show liver adverse events during ETI therapy.<\/jats:p>","DOI":"10.1186\/s12890-024-03114-6","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T05:24:53Z","timestamp":1719897893000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Case Series: Hyperbilirubinemia under elexacaftor\/tezacaftor\/ivacaftor in the presence of Gilbert\u2019s syndrome"],"prefix":"10.1186","volume":"24","author":[{"given":"Julia","family":"Weitzel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Welsner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Taube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Ballmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivagurunathan","family":"Sutharsan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"key":"3114_CR1","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.1016\/S0140-6736(19)32597-8","volume":"394","author":"HGM Heijerman","year":"2019","unstructured":"Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019;394:1940\u20138.","journal-title":"Lancet"},{"key":"3114_CR2","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1056\/NEJMoa1908639","volume":"381","author":"PG Middleton","year":"2019","unstructured":"Middleton PG, Mall MA, D\u0159ev\u00ednek P, Lands LC, McKone EF, Polineni D, Ramsey BW, Taylor-Cousar JL, Tullis E, Vermeulen F, Marigowda G, McKee CM, Moskowitz SM, Nair N, Savage J, Simard C, Tian S, Waltz D, Xuan F, Rowe SM, Jain R. Elexacaftor-tezacaftor-ivacaftor for cystic fibrosis with a single Phe508del allele. 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PMID: 25238538.","DOI":"10.1111\/jgh.12785"}],"container-title":["BMC Pulmonary Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12890-024-03114-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12890-024-03114-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12890-024-03114-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T05:25:24Z","timestamp":1719897924000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpulmmed.biomedcentral.com\/articles\/10.1186\/s12890-024-03114-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,1]]},"references-count":15,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["3114"],"URL":"https:\/\/doi.org\/10.1186\/s12890-024-03114-6","relation":{},"ISSN":["1471-2466"],"issn-type":[{"value":"1471-2466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,1]]},"assertion":[{"value":"29 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"SS has received personal fees or grants from Galapagos, Proteostasis Therapeutics, Celtaxsys, Vertex Pharmaceuticals, Boehringer Ingelheim, Corbus Pharmaceuticals, and Ionis Pharmaceuticals outside the submitted work. Matthias Welsner received personal fees from Vertex Pharmaceuticals, Chiesi, CSL Behring, and Grifols outside of the submitted work. All other authors have no competing interests to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"SS has received personal fees or grants from Galapagos, Proteostasis Therapeutics, Celtaxsys, Vertex Pharmaceuticals, Boehringer Ingelheim, Corbus Pharmaceuticals, and Ionis Pharmaceuticals outside the submitted work. Matthias Welsner received personal fees from Vertex Pharmaceuticals, Chiesi, CSL Behring, and Grifols outside of the submitted work. All other authors have no competing interests to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The studies involving human participants were reviewed and approved by Ethik-Kommission, Universit\u00e4t Duisburg-Essen (no. 19-8797-BO). Written informed consent was obtained from participants and\/or their legal guardian(s) for publication of case report or identifying information\/images in an online open-access publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Patient consent"}},{"value":"Author contributions Study conception: SS, MB. Data acquisition and analysis: JW, SS, MB, MW. Data interpretation: SS, JW, MB, MW, CT. Writing the original manuscript: JW, SS. Revising the work for important intellectual content: JW, MB, SS, MW, CT. All authors contributed to the article and approved the submitted version.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Author contributions"}}],"article-number":"307"}}