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The number of genes underlying the clinical PFIC phenotype is still increasing. While progressive liver disease and its sequelae such as portal hypertension, pruritus and hepatocellular carcinoma determine transplant\u2010free survival, extrahepatic manifestations may cause relevant morbidity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a literature search for extrahepatic manifestations of PFIC associated with pathogenic gene variants in <jats:italic>ATP8B1<\/jats:italic>, <jats:italic>ABCB11<\/jats:italic>, <jats:italic>ABCB4<\/jats:italic>, <jats:italic>TJP2<\/jats:italic>, <jats:italic>NR1H4<\/jats:italic> and <jats:italic>MYO5B<\/jats:italic>. To illustrate the extrahepatic symptoms described in the literature, PFIC cases from our centres were revisited.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Extrahepatic symptoms are common in PFIC subtypes, where the affected gene is expressed at high levels in other tissues. While most liver\u2010associated complications resolve after successful orthotopic liver transplantation (OLT), some extrahepatic symptoms show no response or even worsen after OLT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The spectrum of extrahepatic manifestations in PFIC highlights essential, non\u2010redundant roles of the affected genes in other organs. Extrahepatic features contribute towards low health\u2010related quality of life (HRQOL) and morbidity in PFIC. While OLT is often the only remaining, curative treatment, potential extrahepatic manifestations need to be carefully monitored and addressed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15200","type":"journal-article","created":{"date-parts":[[2022,2,20]],"date-time":"2022-02-20T08:38:15Z","timestamp":1645346295000},"page":"1084-1096","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Extrahepatic manifestations of progressive familial intrahepatic cholestasis syndromes: Presentation of a case series and literature review"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2446-4304","authenticated-orcid":false,"given":"Eva\u2010Doreen","family":"Pfister","sequence":"first","affiliation":[{"name":"Division of Paediatric Gastroenterology and Hepatology, Department of Paediatric Liver, Kidney and Metabolic Diseases Hannover Medical School  Hannover 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