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This study aimed to determine the long\u2010term hepatic safety of lomitapide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were aggregated from the pivotal phase 3 and extension phase clinical trial with lomitapide (median 5.1\u2009years; serum total bilirubin, transaminases, cytokeratin\u201018 [CK\u201018] and enhanced liver fibrosis [ELF] score, fat\u2010soluble vitamins and essential fatty acids), 8\u2010year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) and real\u2010world evidence from a cohort of patients treated with lomitapide in Italy (hepatic elastography, and FIB\u20104 score for hepatic fibrosis).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the phase 3 trial and the LOWER registry, any asymptomatic excursions in liver transaminase levels were not associated with elevations in bilirubin, and no Hy's law cases were detected in up to 8\u2009years follow\u2010up. There were no clinically relevant increases among hepatic biomarkers CK\u201018, CK\u201018 fragments or ELF score and fat\u2010soluble vitamins and essential fatty acids remained above normal levels. In 34 patients treated in Italy with lomita pide for more than 9 \u2009years, elevations in hepatic fat were mild\u2010to\u2010moderate; hepatic stiffness remained normal, and the mean FIB\u20104 score remained below the fibrosis threshold value of 2.67.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data indicate that the hepatic safety of lomitapide remains favourable with no clinically significant elevations in hepatic biomarkers and hepatic stiffness remained normal for more than 9 years follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Phase 3 trial<\/jats:title><jats:p>NCT00730236; extension phase: NCT00943306; LOWER: NCT02135705.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15497","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T09:59:58Z","timestamp":1671098398000},"page":"413-423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Long\u2010term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia"],"prefix":"10.1111","volume":"43","author":[{"given":"Dominique","family":"Larrey","sequence":"first","affiliation":[{"name":"University Hospital of Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"D'Erasmo","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine \u2018Sapienza\u2019 University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sallyann","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Amryt Pharmaceuticals DAC  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Arca","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine \u2018Sapienza\u2019 University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Italian Working Group on 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