{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:15:43Z","timestamp":1787015743751,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T00:00:00Z","timestamp":1754611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006396","name":"Alexion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>In patients with lysosomal acid lipase deficiency (LAL\u2010D), elevations in alanine and aspartate aminotransferases (ALT, AST) are associated with liver damage. The objective of this analysis was to evaluate aminotransferase levels in patients treated with sebelipase alfa enzyme replacement therapy and untreated patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients in this observational study were from the International LAL\u2010D Registry and included untreated and treated patients who started sebelipase alfa at age \u2265\u20096\u2009months. Patients in the longitudinal analysis must have had baseline and longitudinal measures of ALT or AST. A subanalysis was performed on data from patients with 3 consecutive annual follow\u2010up measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 186 patients included in this analysis, 125 were treated with sebelipase alfa. Median age at diagnosis was 9.1 y for treated patients and 20.6 y for untreated patients. Baseline ALT levels were above the upper limit of normal in 93% of children aged &lt;\u200918\u2009years and 68% of adults aged \u2265\u200918\u2009years. Among 53 treated patients who had ALT results reported at 3 consecutive annual measurements, 22 (42%) had ALT levels within normal limits after 1\u2009year of sebelipase alfa treatment. Results were similar for AST. A repeated measures regression model of data from treated patients showed significant reductions from baseline in both ALT and AST levels across 3\u2009years of the study. Untreated patients had no appreciable changes in aminotransferase elevations over time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Aminotransferase levels were elevated in most patients with LAL\u2010D at baseline. There were sustained improvements with sebelipase alfa treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>International LAL\u2010D Registry: NCT01633489, EUPAS13276<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70279","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T06:10:15Z","timestamp":1754719815000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sebelipase Alfa Improves Aminotransferase Levels in Lysosomal Acid Lipase Deficiency: Data From an International Registry"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-3148","authenticated-orcid":false,"given":"Lorenzo","family":"D'Antiga","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery University of Milano\u2013Bicocca  Milan Italy"},{"name":"Pediatric Hepatology, Gastroenterology and Transplantation Hospital Papa Giovanni XXIII  Bergamo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Alexion, AstraZeneca Rare Disease  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-1294","authenticated-orcid":false,"given":"Emilio","family":"Ros","sequence":"additional","affiliation":[{"name":"Institut D'investigacions Biom\u00e8diques August Pi Sunyer (IDIBAPS), hospital Clinic  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Abel","sequence":"additional","affiliation":[{"name":"Department of Global Medical Affairs, Alexion, AstraZeneca Rare Disease  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8047-5011","authenticated-orcid":false,"given":"Manisha","family":"Balwani","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2815-4816","authenticated-orcid":false,"given":"Don P.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Endocrinology Cook Children's Medical Center  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Balistreri","sequence":"additional","affiliation":[{"name":"UC Department of Pediatrics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,8]]},"reference":[{"key":"e_1_2_14_2_1","volume-title":"The Online Metabolic and Molecular Bases of Inherited Disease","author":"Grabowski G. 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