{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T07:53:42Z","timestamp":1740124422140,"version":"3.37.3"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,8,23]],"date-time":"2017-08-23T00:00:00Z","timestamp":1503446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Eculizumab\u2010treated paroxysmal nocturnal hemoglobinuria (PNH<\/jats:styled-content>) patients (pts) show a dramatic decrease in serum lactate dehydrogenase (LDH<\/jats:styled-content>) activities and bilirubin concentrations. However, some pts remain hyperbilirubinemic, possibly indicating an inadequate response due to extravascular hemolysis.<\/jats:p><\/jats:sec>Methods<\/jats:title>Mutation analyses of hepatocanalicular transporter\/nuclear receptor variants (ABCB<\/jats:styled-content>4, ABCB<\/jats:styled-content>11, ATP<\/jats:styled-content>8B1, NR<\/jats:styled-content>1H4<\/jats:italic>) were performed in eight (five of eight males; mean age 38\u00a0years [range 26\u201068\u00a0years]) out of the 174 pts with PNH<\/jats:styled-content>\/\u2010clone at our department due to a persistent increase in total bilirubin concentrations (median 3.4\u00a0mg\/dL<\/jats:styled-content>; range 2.1\u20108.1\u00a0mg\/dL<\/jats:styled-content>) during chronic eculizumab treatment and normal\/or slightly increased serum aminotransferase activities. Median observation time was 70.1\u00a0months (range 10.6\u2010135.2\u00a0months). All pts were treated according to German PNH guidelines.<\/jats:p><\/jats:sec>Results<\/jats:title>Homozygous and heterozygous procholestatic variants in the ABCB<\/jats:styled-content>4<\/jats:italic>, ABCB<\/jats:styled-content>11,<\/jats:italic> and ATP<\/jats:styled-content>8B1<\/jats:italic> genes were identified in all eight pts. All carried the common ABCB<\/jats:styled-content>4<\/jats:italic> c.787A>T polymorphism. The A(TA<\/jats:styled-content>)7<\/jats:sub>TAA<\/jats:styled-content> variant in the UGT<\/jats:styled-content>1A1<\/jats:italic> promoter causing Gilbert syndrome was detected in three pts (5\/8).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Hyperbilirubinemia in PNH<\/jats:styled-content> pts treated with eculizumab might not only be due to an insufficient response but rather a combination of mutations in hepatocanalicular transporter variants, Gilbert syndrome, and extravascular hemolysis. Our findings warrant further studies concerning transporter and enzyme variants in PNH<\/jats:styled-content> to determine their clinical significance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ejh.12927","type":"journal-article","created":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T15:12:52Z","timestamp":1499699572000},"page":"350-356","source":"Crossref","is-referenced-by-count":4,"title":["Persisting hyperbilirubinemia in patients with paroxysmal nocturnal hemoglobinuria (PNH<\/scp>) chronically treated with eculizumab: The role of hepatocanalicular transporter variants"],"prefix":"10.1111","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7530-8892","authenticated-orcid":false,"given":"Ferras","family":"Alashkar","sequence":"first","affiliation":[{"name":"Department of Hematology West German Cancer Center University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne N.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Medicine II Saarland University Medical Center Saarland University Homburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Vance","sequence":"additional","affiliation":[{"name":"Rheinisch\u2010Westf\u00e4lisches Institut f\u00fcr Wirtschaftsforschung Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D\u00f6rte","family":"Herich\u2010Terh\u00fcrne","sequence":"additional","affiliation":[{"name":"Department of Hematology West German Cancer Center University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"D\u00fchrsen","sequence":"additional","affiliation":[{"name":"Department of Hematology West German Cancer Center University Hospital Essen University of Duisburg\u2010Essen Essen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Lammert","sequence":"additional","affiliation":[{"name":"Department of Medicine II Saarland University Medical Center Saarland University Homburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"R\u00f6th","sequence":"additional","affiliation":[{"name":"Department of Hematology West German Cancer Center University Hospital Essen University of Duisburg\u2010Essen Essen 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