{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T20:44:53Z","timestamp":1783975493567,"version":"3.55.0"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Adenosine triphosphate\u2010binding cassette subfamily B member 4 (ABCB4) deficiency may lead to progressive familial intrahepatic cholestasis type 3 (PFIC3), biliary cirrhosis, low phospholipid\u2010associated cholelithiasis (LPAC), intrahepatic cholestasis of pregnancy (ICP), oral contraceptive\u2010induced cholestasis (CIC) or may remain asymptomatic. The long\u2010term course, quality of life and histology were investigated in <jats:italic>ABCB4<\/jats:italic> deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult carriers of <jats:italic>ABCB4<\/jats:italic> gene variants from two regional academic centres were analysed by history taking, electronic patient files, physical examination, blood analysis, abdominal ultrasound (US) and liver elastography. Patients completed a 36\u2010Item Short Form Health Survey (SF\u201036) for quality of life and a Visual Analogue Scale (VAS) for pruritus. Available liver specimens were re\u2010classified according to the Nakanuma scoring system, so far validated for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) only. Quality of life data were compared to published data of patients with PBC, PSC and the general population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010seven patients were identified, 64 (96%) were alive at the time of analysis and 62 (93%) were (at some time) treated with ursodeoxycholic acid (UDCA). Two patients died of cholangiocarcinoma (CCA), and one of decompensated biliary cirrhosis. Three additional deaths of CCA were reported in first\u2010degree relatives. Transplant\u2010free survival was 91% (median follow\u2010up 14\u00a0years). Liver stiffness was normal (&lt;6.3\u00a0kPa) in 75%, intrahepatic stones were detected at ultrasound (US) in 33% and microcalcifications in 22% of cases. Quality of life (n\u00a0=\u00a048) was lower than in the general population particularly in energy\/fatigue and general health domains and comparable to that in PSC. Staging according to Nakanuma in 15 specimens reflected the clinical course.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ABCB4 deficiency has a mild clinical course, but impaired quality of life and limited risk of CCA. The Nakanuma scoring system appears feasible for histological evaluation in ABCB4 deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14662","type":"journal-article","created":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T09:13:59Z","timestamp":1601198039000},"page":"3042-3050","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Carriers of <i>ABCB4<\/i> gene variants show a mild clinical course, but impaired quality of life and limited risk for cholangiocarcinoma"],"prefix":"10.1111","volume":"40","author":[{"given":"Elsemieke","family":"de Vries","sequence":"first","affiliation":[{"name":"Department of Gastroenterology &amp; Hepatology Amsterdam University Medical Centers Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Mazzetti","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology &amp; Hepatology Amsterdam University Medical Centers Amsterdam The Netherlands"},{"name":"Department of Gastroenterology &amp; Hepatology Universit\u00e0 Politecnica delle Marche Ospedali Riuniti di Ancona Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Takkenberg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology &amp; Hepatology Amsterdam University Medical Centers Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahid","family":"Mostafavi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology &amp; Hepatology Amsterdam University Medical Centers Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hennie","family":"Bikker","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Amsterdam University Medical Centers Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6014-6165","authenticated-orcid":false,"given":"Marco","family":"Marzioni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology &amp; 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