{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:46:19Z","timestamp":1792125979319,"version":"4.4.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":87,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Gastroenterol"],"DOI":"10.1186\/s12876-026-05132-6","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T09:13:36Z","timestamp":1784625216000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Gilbert syndrome: exploring the heterozygous UGT1A1 c.41_40dup variant as a potential modifier of bile composition associated with a cholangiopathic phenotype in adults with unexplained chronic cholestasis"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0885-0793","authenticated-orcid":false,"given":"Alessandro","family":"Federico","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2970-9019","authenticated-orcid":false,"given":"Mario","family":"Romeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0519-3049","authenticated-orcid":false,"given":"Fiammetta","family":"Di Nardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2392-3539","authenticated-orcid":false,"given":"Carmine","family":"Napolitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"De Gregorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5473-3440","authenticated-orcid":false,"given":"Claudio","family":"Basile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giusy","family":"Senese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4153-815X","authenticated-orcid":false,"given":"Marcello","family":"Dallio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"issue":"6","key":"5132_CR1","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.mayocp.2015.03.017","volume":"90","author":"KN Lazaridis","year":"2015","unstructured":"Lazaridis KN, LaRusso NF. The cholangiopathies. Mayo Clin Proc. 2015;90(6):791\u2013800. https:\/\/doi.org\/10.1016\/j.mayocp.2015.03.017.","journal-title":"Mayo Clin Proc"},{"issue":"9","key":"5132_CR2","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1136\/gutjnl-2017-315259","volume":"67","author":"GM Hirschfield","year":"2018","unstructured":"Hirschfield GM, Dyson JK, Alexander GJM, Chapman MH, Collier J, H\u00fcbscher S, et al. The British Society of Gastroenterology\/UK-PBC primary biliary cholangitis treatment and management guidelines. Gut. 2018;67(9):1568\u201394. https:\/\/doi.org\/10.1136\/gutjnl-2017-315259.","journal-title":"Gut"},{"issue":"1","key":"5132_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2025.101625","volume":"8","author":"RJ Thompson","year":"2026","unstructured":"Thompson RJ, Vilarinho S, Miquel R, Keitel V. Challenges in the diagnosis and treatment of genetic cholestasis in adults. JHEP Rep. 2026;8(1): 101625. https:\/\/doi.org\/10.1016\/j.jhepr.2025.101625. PubMedPMID:41674895;PubMedCentralPMCID:PMC12890451.","journal-title":"JHEP Rep"},{"issue":"4","key":"5132_CR4","doi-asserted-by":"publisher","first-page":"e152","DOI":"10.1016\/j.jhep.2023.06.012","volume":"79","author":"M Romeo","year":"2023","unstructured":"Romeo M, Dallio M, Federico A. Is it time to reconsider the MRP6 role in bile secretion and LPAC genetic signature? J Hepatol. 2023;79(4):e152\u20134. https:\/\/doi.org\/10.1016\/j.jhep.2023.06.012. PubMed PMID: 37392836.","journal-title":"J Hepatol"},{"key":"5132_CR5","doi-asserted-by":"publisher","unstructured":"Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 2009;4(1). https:\/\/doi.org\/10.1186\/1750-1172-4-1.","DOI":"10.1186\/1750-1172-4-1"},{"issue":"5","key":"5132_CR6","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1007\/s00424-006-0062-9","volume":"453","author":"RPJ Oude Elferink","year":"2007","unstructured":"Oude Elferink RPJ, Paulusma CC. Function and pathophysiological importance of ABCB4 (MDR3 P-glycoprotein). Pflugers Arch - Eur J Physiol. 2007;453(5):601\u201310. https:\/\/doi.org\/10.1007\/s00424-006-0062-9.","journal-title":"Pflugers Arch - Eur J Physiol"},{"issue":"18","key":"5132_CR7","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1056\/nejm199511023331802","volume":"333","author":"PJ Bosma","year":"1995","unstructured":"Bosma PJ, Chowdhury JR, Bakker C, Gantla S, De Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert\u2019s syndrome. N Engl J Med. 1995;333(18):1171\u20135. https:\/\/doi.org\/10.1056\/nejm199511023331802.","journal-title":"N Engl J Med"},{"issue":"3","key":"5132_CR8","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.bcmd.2012.01.004","volume":"48","author":"C Rodrigues","year":"2012","unstructured":"Rodrigues C, Vieira E, Santos R, de Carvalho J, Santos-Silva A, Costa E, et al. Impact of UGT1A1 gene variants on total bilirubin levels in Gilbert syndrome patients and in healthy subjects. Blood Cells Mol Dis. 2012;48(3):166\u201372. https:\/\/doi.org\/10.1016\/j.bcmd.2012.01.004. PubMed PMID: 22325916.","journal-title":"Blood Cells Mol Dis"},{"issue":"8","key":"5132_CR9","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1136\/gut.21.8.650","volume":"21","author":"P Duvaldestin","year":"1980","unstructured":"Duvaldestin P, Mahu JL, Metreau JM, Arondel J, Preaux AM, Berthelot P. Possible role of a defect in hepatic bilirubin glucuronidation in the initiation of cholesterol gallstones. Gut. 1980;21(8):650\u20135. https:\/\/doi.org\/10.1136\/gut.21.8.650.","journal-title":"Gut"},{"issue":"9001","key":"5132_CR10","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/s0140-6736(96)91273-8","volume":"347","author":"G Monaghan","year":"1996","unstructured":"Monaghan G, Ryan M, Hume R, Burchell B, Seddon R. Genetic variation in bilirubin UDP-glucuronosyltransferase gene promoter and Gilbert\u2019s syndrome. Lancet. 1996;347(9001):578\u201381. https:\/\/doi.org\/10.1016\/s0140-6736(96)91273-8.","journal-title":"Lancet"},{"issue":"11","key":"5132_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2022.100590","volume":"4","author":"M Biyoukar","year":"2022","unstructured":"Biyoukar M, Corpechot C, El Mouhadi S, Chambenois E, Vanderbecq Q, Barbu V, et al. A BCB4 variant is associated with hepatobiliary MR abnormalities in people with low-phospholipid-associated cholelithiasis syndrome. JHEP Rep. 2022;4(11): 100590. https:\/\/doi.org\/10.1016\/j.jhepr.2022.100590. PubMedPMID:36277956;PubMedCentralPMCID: PMC9582794.","journal-title":"JHEP Rep"},{"issue":"2","key":"5132_CR12","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.jid.2018.12.004","volume":"139","author":"S Erickson","year":"2019","unstructured":"Erickson S, Kim BS. Research Techniques Made Simple: Itch Measurement in Clinical Trials. J Invest Dermatol. 2019;139(2):264-269.e1. https:\/\/doi.org\/10.1016\/j.jid.2018.12.004. PubMedPMID:30665580; PubMedCentralPMCID:PMC8922716.","journal-title":"J Invest Dermatol"},{"key":"5132_CR13","doi-asserted-by":"publisher","unstructured":"Lipi\u0144ski P, Ciara E, Jurkiewicz D, Pollak A, Wypch\u0142o M, P\u0142oski R, et al. Targeted Next-Generation Sequencing in Diagnostic Approach to Monogenic Cholestatic Liver Disorders\u2014Single-Center Experience. Front Pediatr. 2020;8. https:\/\/doi.org\/10.3389\/fped.2020.00414.","DOI":"10.3389\/fped.2020.00414"},{"key":"5132_CR14","doi-asserted-by":"publisher","unstructured":"Castillo-Casta\u00f1eda SM, Rivera-Espinosa L, G\u00f3mez-Gardu\u00f1o J, Cordova-Gallardo J, Ch\u00e1vez-Pacheco JL, M\u00e9ndez-S\u00e1nchez N. Identification and quantification of the molecular species of bilirubin BDG, BMG and UCB by LC\u2012MS\/MS in hyperbilirubinemic human serum. Haggag YA, editor. PLoS ONE. 2024;19(11):e0313044. https:\/\/doi.org\/10.1371\/journal.pone.0313044.","DOI":"10.1371\/journal.pone.0313044"},{"issue":"6","key":"5132_CR15","doi-asserted-by":"publisher","first-page":"657","DOI":"10.3109\/00365528909093105","volume":"24","author":"V Skar","year":"1989","unstructured":"Skar V, Saxerholt H. High-performance liquid chromatography of bilirubin conjugates in bile: effect of beta-glucuronidase on the bile pigments. Scand J Gastroenterol. 1989;24(6):657\u201365. https:\/\/doi.org\/10.3109\/00365528909093105. PubMed PMID: 2814336.","journal-title":"Scand J Gastroenterol"},{"issue":"3","key":"5132_CR16","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1042\/bj2250787","volume":"225","author":"W Spivak","year":"1985","unstructured":"Spivak W, Carey MC. Reverse-phase h.p.l.c. separation, quantification and preparation of bilirubin and its conjugates from native bile. Quantitative analysis of the intact tetrapyrroles based on h.p.l.c. of their ethyl anthranilate azo derivatives. Biochem J. 1985;225(3):787\u2013805. https:\/\/doi.org\/10.1042\/bj2250787.","journal-title":"Biochem J"},{"issue":"7","key":"5132_CR17","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1111\/liv.15592","volume":"43","author":"CF Murillo Perez","year":"2023","unstructured":"Murillo Perez CF, Ioannou S, Hassanally I, Trivedi PJ, Corpechot C, van der Meer AJ, et al. Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one-year non-responders and predicts survival. Liver Int. 2023;43(7):1497\u2013506. https:\/\/doi.org\/10.1111\/liv.15592. PubMed PMID: 37157905.","journal-title":"Liver Int"},{"issue":"6","key":"5132_CR18","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/0168-8278(95)80226-6","volume":"22","author":"K Ishak","year":"1995","unstructured":"Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22(6):696\u20139. https:\/\/doi.org\/10.1016\/0168-8278(95)80226-6. PubMed PMID: 7560864.","journal-title":"J Hepatol"},{"issue":"15","key":"5132_CR19","doi-asserted-by":"publisher","first-page":"8181","DOI":"10.3390\/ijms25158181","volume":"25","author":"SM Castillo-Casta\u00f1eda","year":"2024","unstructured":"Castillo-Casta\u00f1eda SM, Cordova-Gallardo J, Rivera-Espinosa L, Chavez-Pacheco JL, Ram\u00edrez-Mej\u00eda MM, M\u00e9ndez-S\u00e1nchez N. Bilirubin Molecular Species Play an Important Role in the Pathophysiology of Acute-on-Chronic Liver Failure. Int J Mol Sci. 2024;25(15):8181. https:\/\/doi.org\/10.3390\/ijms25158181. PubMedPMID: 39125751;PubMedCentralPMCID:PMC11311833.","journal-title":"Int J Mol Sci"},{"issue":"5","key":"5132_CR20","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/0022-4804(91)90032-h","volume":"50","author":"HS Kaufman","year":"1991","unstructured":"Kaufman HS, Magnuson TH, Webb TH, Watt PC, Fox-Talbot MK, Pitt HA, et al. Bilirubin monoglucuronide promotes cholesterol gallstone formation. J Surg Res. 1991;50(5):504\u20139. https:\/\/doi.org\/10.1016\/0022-4804(91)90032-h. PubMed PMID: 2038190.","journal-title":"J Surg Res"},{"issue":"9","key":"5132_CR21","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.3748\/wjg.v30.i9.1189","volume":"30","author":"JL Jiang","year":"2024","unstructured":"Jiang JL, Zhou YY, Zhong WW, Luo LY, Liu SY, Xie XY, et al. Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury. World J Gastroenterol. 2024;30(9):1189\u2013212. https:\/\/doi.org\/10.3748\/wjg.v30.i9.1189. PubMedPMID:38577195; PubMedCentralPMCID: PMC10989491.","journal-title":"World J Gastroenterol"},{"issue":"2","key":"5132_CR22","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1007\/s00330-021-08147-7","volume":"32","author":"SK Venkatesh","year":"2022","unstructured":"Venkatesh SK, Welle CL, Miller FH, Jhaveri K, Ringe KI, Eaton JE, et al. Reporting standards for primary sclerosing cholangitis using MRI and MR cholangiopancreatography: guidelines from MR Working Group of the International Primary Sclerosing Cholangitis Study Group. Eur Radiol. 2022;32(2):923\u201337. https:\/\/doi.org\/10.1007\/s00330-021-08147-7. PubMed PMID: 34363134.","journal-title":"Eur Radiol"}],"container-title":["BMC Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12876-026-05132-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-026-05132-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12876-026-05132-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:08:51Z","timestamp":1792123731000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12876-026-05132-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["5132"],"URL":"https:\/\/doi.org\/10.1186\/s12876-026-05132-6","relation":{},"ISSN":["1471-230X"],"issn-type":[{"value":"1471-230X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"assertion":[{"value":"15 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study received approval by the ethical committee of the University of Campania Luigi Vanvitelli in Naples (Ethical Committee approval\u2014study protocol n.0034563\/i-2023). All study participants, or their legal guardians, provided informed written consent before enrolment in this study.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"657"}}