{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:48:27Z","timestamp":1793296107799,"version":"4.5.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2018,11,17]],"date-time":"2018-11-17T00:00:00Z","timestamp":1542412800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,11,17]],"date-time":"2018-11-17T00:00:00Z","timestamp":1542412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>Currently, there are no interferon\u2010free treatments available for hepatitis C virus (HCV)\u2013infected patients younger than 12 years. We evaluated the safety and effectiveness of the all\u2010oral regimen ledipasvir\u2013sofosbuvir \u00b1 ribavirin in HCV\u2010infected children aged 6 to &lt;12 years.\u00a0In an open\u2010label study, patients aged 6 to &lt;12 years received ledipasvir 45 mg\u2013sofosbuvir 200 mg as two fixed\u2010dose combination tablets 22.5\/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety\u2010two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6\u201011). Most were perinatally infected (97%) and treatment\u2010naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91\/92; 95% confidence interval, 94%\u2010100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common\u00a0adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration\u2013time curve and maximum concentration values for sofosbuvir, its primary metabolite GS\u2010331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%\u2010200%) compared to values in adults in phase 2\/3 of the ledipasvir and sofosbuvir studies. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> Ledipasvir\u2013sofosbuvir was well tolerated and highly effective in children 6 to &lt;12 years old with chronic HCV.<\/jats:p>","DOI":"10.1002\/hep.30123","type":"journal-article","created":{"date-parts":[[2018,8,6]],"date-time":"2018-08-06T22:16:04Z","timestamp":1533593764000},"page":"2158-2166","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":96,"title":["Safety and Efficacy of Ledipasvir\u2013Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6\u201011"],"prefix":"10.1097","volume":"68","author":[{"given":"Karen F.","family":"Murray","sequence":"first","affiliation":[{"name":"University of Washington and Seattle Children's Hospital,Seattle,WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F.","family":"Balistreri","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Bansal","sequence":"additional","affiliation":[{"name":"Kings College Hospital,London,UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Whitworth","sequence":"additional","affiliation":[{"name":"Cook Children\u2019s Health Care System,Fort Worth,TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Evans","sequence":"additional","affiliation":[{"name":"Auckland Clinical Studies and Starship Child Health,Auckland,New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regino 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