{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T02:22:34Z","timestamp":1778034154234,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,8,3]],"date-time":"2015-08-03T00:00:00Z","timestamp":1438560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Increased life expectancy in sickle cell disease (<jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>) has resulted in greater recognition of the consequences of repeated intravascular vaso\u2010occlusion and chronic haemolysis to multiple organ systems.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To report the long\u2010term consequences of liver dysfunction in <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A cohort of <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> patients was prospectively evaluated at the National Institutes of Health (<jats:styled-content style=\"fixed-case\">NIH<\/jats:styled-content>) Clinical Center. The association of mortality with liver enzymes, parameters of liver synthetic function and iron overload was evaluated using Cox regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exactly, 247 <jats:styled-content style=\"fixed-case\">SCD<\/jats:styled-content> patients were followed up for 30\u00a0months of whom 22 (9%) died. After controlling for predictors, increased direct bilirubin (<jats:styled-content style=\"fixed-case\">DB<\/jats:styled-content>), ferritin, alkaline phosphatase and decreased albumin were independently associated with mortality. In a multivariable model, only high <jats:styled-content style=\"fixed-case\">DB<\/jats:styled-content> and ferritin remained significant. Ferritin correlated with hepatic iron content and total blood transfusions but not haemolysis markers. Forty patients underwent liver biopsies and 11 (28%) had fibrosis. Twelve of 26 patients (48%) had portal hypertension by hepatic venous pressure gradient (<jats:styled-content style=\"fixed-case\">HVPG<\/jats:styled-content>) measurements. All patients with advanced liver fibrosis had iron overload; however, most patients (69%) with iron overload were without significant hepatic fibrosis. Ferritin did not correlate with left ventricular dysfunction by echocardiography. <jats:styled-content style=\"fixed-case\">DB<\/jats:styled-content> correlated with bile acid levels suggesting liver pathology. Platelet count and soluble <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>14 correlated with <jats:styled-content style=\"fixed-case\">HVPG<\/jats:styled-content> indicating portal hypertension.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ferritin and <jats:styled-content style=\"fixed-case\">direct bilirubin<\/jats:styled-content> are independently associated with mortality in <jats:styled-content style=\"fixed-case\">sickle cell disease<\/jats:styled-content>. Ferritin likely relates to transfusional iron overload, while <jats:styled-content style=\"fixed-case\">direct bilirubin<\/jats:styled-content> suggests impairment of hepatic function, possibly impairing patients\u2019 ability to tolerate systemic insults.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.13347","type":"journal-article","created":{"date-parts":[[2015,8,3]],"date-time":"2015-08-03T07:55:22Z","timestamp":1438588522000},"page":"912-921","source":"Crossref","is-referenced-by-count":60,"title":["Liver injury is associated with mortality in sickle cell disease"],"prefix":"10.1111","volume":"42","author":[{"given":"J. J.","family":"Feld","sequence":"first","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases (NIDDK) National Institutes of Health (NIH) Bethesda MD USA"},{"name":"Toronto Centre for Liver Disease Sandra Rotman Center for Global Health University of Toronto Toronto ON Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. J.","family":"Kato","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute (NHLBI) National Institutes of Health (NIH) Bethesda MD USA"},{"name":"Vascular Medicine Institute University of Pittsburgh Medical Center Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Koh","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases (NIDDK) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Shields","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute (NHLBI) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Hildesheim","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute (NHLBI) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. E.","family":"Kleiner","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology National Cancer Institute National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"VI","given":"J. G.","family":"Taylor","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute (NHLBI) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. G.","family":"Sandler","sequence":"additional","affiliation":[{"name":"Human Immunology Section Vaccine Research Center National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Douek","sequence":"additional","affiliation":[{"name":"Human Immunology Section Vaccine Research Center National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Haynes\u2010Williams","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases (NIDDK) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. S.","family":"Nichols","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute (NHLBI) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. H.","family":"Hoofnagle","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases (NIDDK) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Jake Liang","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases (NIDDK) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. T.","family":"Gladwin","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute (NHLBI) National Institutes of Health (NIH) Bethesda MD USA"},{"name":"Vascular Medicine Institute University of Pittsburgh Medical Center Pittsburgh PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Heller","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch National Institute of Diabetes &amp; Digestive &amp; Kidney Diseases (NIDDK) National Institutes of Health (NIH) Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2003.04594.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-11-3758"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.358"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199406093302303"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(80)80008-8"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20685"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-013-9873-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21524"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013755029891"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2005.12.013"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035477"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.33715"},{"key":"e_1_2_8_14_1","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1128\/IAI.66.3.1135-1141.1998","article-title":"Endotoxin binding and elimination by monocytes: secretion of soluble CD14\u00a0represents an inducible mechanism counteracting reduced expression of membrane CD14 in patients with sepsis and in a patient with paroxysmal nocturnal hemoglobinuria","volume":"66","author":"Hiki N","year":"1998","journal-title":"Infect Immun"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4804(91)90143-A"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20049"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e31802df0fe"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21215"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V89.3.739"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20809"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20402"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0037-1963(01)90060-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2007.08.009"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2001.24114"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20024"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06082.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.30082"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(95)80424-2"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1999.01293.x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.02.081"}],"container-title":["Alimentary Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapt.13347","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapt.13347","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apt.13347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T11:00:24Z","timestamp":1694430024000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apt.13347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,3]]},"references-count":29,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1111\/apt.13347"],"URL":"https:\/\/doi.org\/10.1111\/apt.13347","archive":["Portico"],"relation":{},"ISSN":["0269-2813","1365-2036"],"issn-type":[{"value":"0269-2813","type":"print"},{"value":"1365-2036","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,8,3]]}}}