{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:16:28Z","timestamp":1788336988474,"version":"build-2803163510"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2018,3,22]],"date-time":"2018-03-22T00:00:00Z","timestamp":1521676800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Communications"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Genetic variants in the adenosine triphosphate\u2010binding cassette subfamily B member 4 (<jats:italic toggle=\"yes\">ABCB4<\/jats:italic>) gene, which encodes hepatocanalicular phosphatidylcholine floppase, can lead to different phenotypes, such as progressive familial intrahepatic cholestasis (PFIC) type 3, low phospholipid\u2010associated cholelithiasis, and intrahepatic cholestasis of pregnancy. The aim of this multicenter project was to collect information on onset and progression of this entity in different age groups and to assess the relevance of this disease for the differential diagnosis of chronic liver disease. Clinical and laboratory data of 38 patients (17 males, 21 females, from 29 families) with homozygous or (compound) heterozygous <jats:italic toggle=\"yes\">ABCB4<\/jats:italic> mutations were retrospectively collected. For further analysis, patients were grouped according to the age at clinical diagnosis of <jats:italic toggle=\"yes\">ABCB4<\/jats:italic>\u2010associated liver disease into younger age (&lt;18 years) or adult age (\u226518 years). All 26 patients diagnosed in childhood presented with pruritus (median age 1 year). Hepatomegaly and splenomegaly were present in 85% and 96% of these patients, respectively, followed by jaundice (62%) and portal hypertension (69%). Initial symptoms preceded diagnosis by 1 year, and 13 patients received a liver transplant (median age 6.9 years). Of note, 9 patients were misdiagnosed as biliary atresia, Alagille syndrome, or PFIC type 1. In the 12 patients with diagnosis in adulthood, the clinical phenotype was generally less severe, including intrahepatic cholestasis of pregnancy, low phospholipid\u2010associated cholelithiasis, or (non)cirrhotic PFIC3. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> ABCB4 deficiency with onset in younger patients caused a more severe PFIC type 3 phenotype with the need for liver transplantation in half the children. Patients with milder phenotypes are often not diagnosed before adulthood. One third of the children with PFIC type 3 were initially misdiagnosed, indicating the need for better diagnostic tools and medical education. 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Center,Homburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Keitel\u2010Anselmo","sequence":"additional","affiliation":[{"name":"University Hospital, Heinrich Heine University D\u00fcsseldorf, Department of Gastroenterology, Hepatology and Infectious Diseases,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Kubitz","sequence":"additional","affiliation":[{"name":"University Hospital, Heinrich Heine University D\u00fcsseldorf, Department of Gastroenterology, Hepatology and Infectious Diseases,D\u00fcsseldorf,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Medicine II,Saarland University Medical Center,Homburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Gerner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Gastroenterology, Clinic for Pediatrics II,University Hospital, University Essen,Essen,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva\u2010Doreen","family":"Pfister","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver, and Metabolic Diseases,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imeke","family":"Goldschmidt","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver, and Metabolic Diseases,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman","family":"Junge","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver, and Metabolic Diseases,Hannover,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Wenning","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics,University Hospital,Heidelberg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Gehring","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,University Medical Center of the Johannes Gutenberg University Mainz,Mainz,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Arens","sequence":"additional","affiliation":[{"name":"Klinikum Kassel,Pediatric Gastroenterology,Kassel,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Bretschneider","sequence":"additional","affiliation":[{"name":"Klinik St. Marienstift,Magdeburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Grothues","sequence":"additional","affiliation":[{"name":"KUNO University Children's Hospital,Regensburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Engelmann","sequence":"additional","affiliation":[{"name":"Lukaskrankenhaus,Children's Hospital,Neuss,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lammert","sequence":"additional","affiliation":[{"name":"Department of Medicine II,Saarland University Medical Center,Homburg,Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Baumann","sequence":"additional","affiliation":[{"name":"Hannover Medical School, Division of Pediatric Gastroenterology and Hepatology, Department of Pediatric Kidney, Liver, and Metabolic Diseases,Hannover,Germany"},{"name":"Institute of Immunology and Immunotherapy,University of 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