{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T17:55:58Z","timestamp":1782842158133,"version":"3.54.5"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Biallelic variants in the adenosine triphosphate\u00a0binding cassette subfamily B member 4 (<jats:italic>ABCB4<\/jats:italic>) gene which encodes the multidrug resistance 3 protein (MDR3) leads to progressive familiar intrahepatic cholestasis type 3. However, monoallelic variants are increasingly recognized as contributing to liver disease in adults. Our aim was to describe the clinical characteristics of MDR3 heterozygous variants in a large cohort of infants and children with cholestatic liver disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The clinical and genotypic data on pediatric patients seen at King's College Hospital, London, between 2004 and 2022 and found to harbour heterozygous variants in <jats:italic>ABCB4<\/jats:italic> were reviewed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ninety\u2010two patients amongst 1568 tested were identified with a monoallelic variant (5.9%). The most common presenting problem was conjugated hyperbilirubinemia (<jats:italic>n<\/jats:italic>\u2009=\u200946; 50%) followed by cholelithiasis (<jats:italic>n<\/jats:italic>\u2009=\u200912; 13%) and cholestatic hepatitis (<jats:italic>n<\/jats:italic>\u2009=\u200910; 11%). The median values of liver biochemistry at presentation were: GGT 105 IU\/L and total bilirubin 86 \u00b5mol\/L. Thirty\u2010two genetic variants were identified including 22 missense (69%), 4 deletions (13%), 5 splice site (16%) and 1 termination (3%). At a median follow up of 1 year there was resolution of liver disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Rare variants in <jats:italic>ABCB4<\/jats:italic> were found amongst infants and children with cholestatic liver disease. The presenting problems were variable and abnormalities tended to normalize over time. Those with severe mutations could develop liver disease later in life when exposed to further insult and should be counseled appropriately.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jpn3.12080","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T23:47:38Z","timestamp":1702424858000},"page":"339-349","source":"Crossref","is-referenced-by-count":11,"title":["Clinical outcomes of ABCB4 heterozygosity in infants and children with cholestatic liver disease"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5893-6464","authenticated-orcid":false,"given":"Robert","family":"Hegarty","sequence":"first","affiliation":[{"name":"Paediatric Liver, GI &amp; Nutrition Centre King's College Hospital London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Gurra","sequence":"additional","affiliation":[{"name":"King's College London London 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