{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:02:47Z","timestamp":1787317367927,"version":"build-2736575974"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T00:00:00Z","timestamp":1364428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Cholesteryl ester storage disease (CESD), an inherited deficiency of lysosomal acid lipase (LAL), is an underappreciated cause of progressive liver disease with no approved therapy. Presenting features include dyslipidemia, elevated transaminases, and hepatomegaly. To assess the clinical effects and safety of the recombinant human LAL, sebelipase alfa, nine patients received four once-weekly infusions (0.35, 1, or 3 mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) in LAL-CL01, which is the first human study of this investigational agent. Patients completing LAL-CL01 were eligible to enroll in the extension study (LAL-CL04) in which they again received four once-weekly infusions of sebelipase alfa (0.35, 1, or 3 mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) before transitioning to long-term every-other-week infusions (1 or 3 mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). Sebelipase alfa was well tolerated, with mostly mild adverse events unrelated to sebelipase alfa. No antidrug antibodies were detected. Transaminases decreased in patients in LAL-CL01 and increased between studies. In seven patients receiving ongoing sebelipase alfa treatment in LAL-CL04, the mean \u00b1 standard deviation (SD) decreases for alanine transaminase and aspartate aminotransferase at week 12 compared to the baseline values in LAL-CL01 were 46 \u00b1 21 U\/L (\u221252%) and 21 \u00b1 14 U\/L (\u221236%), respectively (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2264 0.05). Through week 12 of LAL-CL04, these seven patients also showed mean decreases from baseline in total cholesterol of 44 \u00b1 41 mg\/dL (\u221222%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.047), low density lipoprotein-cholesterol of 29 \u00b1 31 mg\/dL (\u221227%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.078), and triglycerides of 50 \u00b1 38 mg\/dL (\u221228%,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.016) and increases in high density lipoprotein-cholesterol of 5 mg\/dL (15%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.016).\n                      <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>\n                      : These data establish that sebelipase alfa, an investigational enzyme replacement, in patients with CESD is well tolerated, rapidly decreases serum transaminases, and that these improvements are sustained with long-term dosing and are accompanied by improvements in serum lipid profile. (HEPATOLOGY 2013;58:950\u2013957)\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/hep.26289","type":"journal-article","created":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T11:03:43Z","timestamp":1359025423000},"page":"950-957","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":100,"title":["Clinical Effect And Safety Profile of Recombinant Human Lysosomal Acid Lipase in Patients With Cholesteryl Ester Storage Disease"],"prefix":"10.1097","volume":"58","author":[{"given":"Manisha","family":"Balwani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Breen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Enns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick B.","family":"Deegan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Honz\u00edk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Kane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Malinova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reena","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eveline O.","family":"Stock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassili","family":"Valayannopoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmond J.","family":"Wraith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Burg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Eckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony G.","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R2-16-20241201","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/S0022-3476(77)80557-X","article-title":"Cholesterol ester storage disease: clinical, biochemical, and pathological studies.","volume":"90","author":"Beaudet","year":"1977","journal-title":"J Pediatr"},{"key":"R3-16-20241201","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/PL00008203","article-title":"Testis a novel storage site in human cholesteryl ester storage disease. 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