{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:21:05Z","timestamp":1761920465891,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T00:00:00Z","timestamp":1533513600000},"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":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Clinical syndromes associated with biallelic mutations of bile acid (BA) transporters usually present in childhood. Subtle mutations may underlie intrahepatic cholestasis of pregnancy (ICP) and oral contraceptive steroid (OCS) induced cholestasis. In five women with identified genetic mutations of such transporters, with eight observed pregnancies complicated by ICP, we examined relationships between transporter mutations, clinical phenotypes, and treatment outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gene mutation analysis for BA transporter deficiencies was performed using Next Generation\/Sanger sequencing, with analysis for gene deletions\/duplications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intrahepatic cholestasis of pregnancy was early\u2010onset (9\u201332\u00a0weeks gestation) and severe (peak BA 74\u2013370\u00a0\u03bcmol\/L), with premature delivery (28<jats:sup>+1<\/jats:sup>\u201337<jats:sup>0<\/jats:sup> weeks gestation) in 7\/8 pregnancies, <jats:italic>in utero<\/jats:italic> passage of meconium in 4\/8, but overall good perinatal outcomes, with no stillbirths. There was generally no response to ursodeoxycholic acid and variable responses to rifampicin and chelation therapies; naso\u2010biliary drainage appeared effective in 2\/2 episodes persisting post\u2010partum in each of the two sisters. Episodic jaundice occurring spontaneously or provoked by non\u2010specific infections, and OCS\u2010induced cholestasis, had previously occurred in 3\/5 women. Two cases showed biallelic heterozygosity for several <jats:italic>ABCB11<\/jats:italic> mutations, one was homozygous for an <jats:italic>ABCB4<\/jats:italic> mutation and a fourth case was heterozygous for another <jats:italic>ABCB4<\/jats:italic> mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Early\u2010onset or recurrent ICP, especially with previous spontaneous or OCS\u2010induced episodes of cholestasis and\/or familial cholestasis, may be attributable to transporter mutations, including biallelic mutations of one or more transporters. Response to standard therapies for ICP is often incomplete; BA sequestering therapy or naso\u2010biliary drainage may be effective. Optimized management can produce good outcomes despite premature birth and evidence of fetal compromise.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.14376","type":"journal-article","created":{"date-parts":[[2018,7,11]],"date-time":"2018-07-11T02:38:59Z","timestamp":1531276739000},"page":"425-435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Biliary transporter gene mutations in severe intrahepatic cholestasis of pregnancy: Diagnostic and management implications"],"prefix":"10.1111","volume":"34","author":[{"given":"Sze Pheh","family":"Yeap","sequence":"first","affiliation":[{"name":"Liver Unit Royal Adelaide Hospital  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh","family":"Harley","sequence":"additional","affiliation":[{"name":"Liver Unit Royal Adelaide Hospital  Adelaide South Australia Australia"},{"name":"Department of Medicine University of Adelaide  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Thompson","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies King's College Hospital  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate Diana","family":"Williamson","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine University of Oxford  Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Bate","sequence":"additional","affiliation":[{"name":"Liver Unit Royal Adelaide Hospital  Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farah","family":"Sethna","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Canberra Hospital  Canberra Australian Capital Territory Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Farrell","sequence":"additional","affiliation":[{"name":"Liver Research Unit Canberra Hospital  Canberra Australian Capital Territory Australia"},{"name":"The Australian National University Medical School  Canberra Australian Capital Territory Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5355-2955","authenticated-orcid":false,"given":"William \u201cBill\u201d","family":"Hague","sequence":"additional","affiliation":[{"name":"Obstetric Medicine Women's and Children's Hospital  North Adelaide South Australia Australia"},{"name":"Robinson Research Institute University of Adelaide  North Adelaide South Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,8,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(00)00078-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-19038"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-960172"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20285"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2918"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1147"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10713"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.038"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/petr.12889"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2015.06.002"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.15.2049"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.406"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.04.009"},{"key":"e_1_2_7_15_1","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD000493.pub2","article-title":"Interventions for treating cholestasis in pregnancy","author":"Gurung V","year":"2013","journal-title":"Cochrane Database Syst. 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