{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T15:51:28Z","timestamp":1778946688859,"version":"3.51.4"},"reference-count":19,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81070281"],"award-info":[{"award-number":["81070281"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective:<\/jats:title><jats:p>The aims of the present study was to study the significance of <jats:italic>ABCB4<\/jats:italic> mutations in mainland Chinese children with chronic intrahepatic cholestasis and to correlate genetic findings with clinical features and response to ursodeoxycholic acid (UDCA) therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Thirteen patients with chronic intrahepatic cholestasis and elevated serum \u03b3\u2010glutamyl transpeptidase activity of unknown cause were enrolled in a single pediatric center. All of the encoding exons and flanking areas of <jats:italic>ABCB4<\/jats:italic> were sequenced. Available liver biopsy specimens were immunostained for multidrug resistance protein 3. The clinical features, biochemical parameters, and responses to therapy were compared with patients with or without <jats:italic>ABCB4<\/jats:italic> mutation(s).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Six different <jats:italic>ABCB4<\/jats:italic> mutations were identified in 3 patients; each patient was a compound heterozygote. Apart from c.139C&gt;T (p.R47X), all were novel, including c.344+2_+3insT, c.1376A&gt;G (p.D459G), c.1745G&gt;A (p.R582Q), c.2077_2078delC (p.P693HfsX698), and c.3825_3826delA (p.M1276WfsX1308). Absent or reduced multidrug resistance protein 3 canalicular immunostaining was demonstrated in patients with <jats:italic>ABCB4<\/jats:italic> mutations. Serum total bile acid levels were higher in patients with <jats:italic>ABCB4<\/jats:italic> mutations than in patients without <jats:italic>ABCB4<\/jats:italic> mutations (352.5 \u00b1 97.0 vs 55.9 \u00b1 50.4 \u03bcmol\/L, <jats:italic>P<\/jats:italic> = 7.32E\u201005). There was no difference in other biochemical parameters between patients with and without <jats:italic>ABCB4<\/jats:italic> mutations. After oral UDCA administration in 3 patients with <jats:italic>ABCB4<\/jats:italic> mutations, pruritus disappeared, growth improved, spleen size decreased, and platelet counts increased. In the 10 patients without <jats:italic>ABCB4<\/jats:italic> mutations, an inconsistent response to UDCA therapy was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>In mainland Chinese children, some cases of chronic intrahepatic cholestasis with high \u03b3\u2010glutamyl transpeptidase could be attributed to <jats:italic>ABCB4<\/jats:italic> mutations. UDCA administration partially improved clinical symptoms and liver function.<\/jats:p><\/jats:sec>","DOI":"10.1097\/mpg.0b013e31824ef36f","type":"journal-article","created":{"date-parts":[[2012,2,15]],"date-time":"2012-02-15T09:42:00Z","timestamp":1329298920000},"page":"150-156","source":"Crossref","is-referenced-by-count":19,"title":["Chinese Children With Chronic Intrahepatic Cholestasis and High \u03b3\u2010Glutamyl Transpeptidase"],"prefix":"10.1002","volume":"55","author":[{"given":"Ling\u2010Juan","family":"Fang","sequence":"first","affiliation":[{"name":"Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao\u2010Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.S.","family":"Knisely","sequence":"additional","affiliation":[{"name":"Institute of Liver Studies King's College Hospital Denmark Hill London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian\u2010She","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Pediatric Liver Diseases Children's Hospital of Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181c1b368"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2009.02112.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230435"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.23984"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181596060"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1987.tb02653.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)67788-4"},{"key":"e_1_2_7_9_1","first-page":"638","article-title":"Tissue distribution of the human MDR3 P\u2010glycoprotein","volume":"71","author":"Smit JJ","year":"1994","journal-title":"Lab Invest"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90380-9"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-006-0062-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201908"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0b013e3181f50363"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1273427"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.1.282"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2011.03.004"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200107000-00011"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2010.28"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkf493"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.03.044"}],"container-title":["Journal of Pediatric Gastroenterology and Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1097\/MPG.0b013e31824ef36f","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T13:26:13Z","timestamp":1705584373000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1097\/MPG.0b013e31824ef36f"}},"subtitle":["Clinical Features and Association With <i>ABCB4<\/i> Mutations"],"short-title":[],"issued":{"date-parts":[[2012,8]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,8]]}},"alternative-id":["10.1097\/MPG.0b013e31824ef36f"],"URL":"https:\/\/doi.org\/10.1097\/mpg.0b013e31824ef36f","archive":["Portico"],"relation":{},"ISSN":["0277-2116","1536-4801"],"issn-type":[{"value":"0277-2116","type":"print"},{"value":"1536-4801","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,8]]}}}