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The aim of this work was to assess the efficacy and safety of oral DAAs in HCV-infected children with associated comorbidities. This analytical retrospective study included children with HCV mono-infection versus those with associated comorbidities. The study included 187 HCV-infected children aged 6\u201318\u00a0years; 114 patients (61%) had associated comorbidities. The most frequent comorbidities were hematological disorders (30.7%), followed by renal and cardiac diseases. Baseline total bilirubin, aspartate aminotransferase, and gamma glutamyl transpeptidase were significantly more elevated in patients with comorbidities. Sustained virologic response (SVR) was achieved in 100% of patients with HCV mono-infection versus 98.2% of patients with comorbidities. The most frequently reported treatment adverse effects were headache, asthenia, and irritability. All side effects were transient and did not necessitate treatment discontinuation. <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusion<\/jats:italic>: DAAs allowed treatment of HCV-infected children with comorbidities with high SVR and excellent safety profile. Treatment with sofosbuvir\/ledipasvir achieved an SVR of 98.9% in HCV-infected children with comorbidities. Treatment was safe and well tolerated with mild transient adverse events.\n<jats:table-wrap>\n              <jats:table>\n                <jats:tbody>\n                  <jats:tr>\n                    <jats:td align=\"left\" colspan=\"2\">\n                      <jats:bold>What is Known<\/jats:bold>:\u2022 <jats:italic>The novel DAAs have revolutionized the landscape of HCV treatment and enabled the treatment of those who could not be treated using IFN.<\/jats:italic>\u2022 <jats:italic>When treating HCV, clinicians should take into consideration the presence of other comorbid conditions.<\/jats:italic>\n                      <jats:italic>In the IFN-RBV era, many HCV patients with comorbidities were ineligible for therapy<\/jats:italic>.<\/jats:td>\n                  <\/jats:tr>\n                  <jats:tr>\n                    <jats:td align=\"left\" colspan=\"2\">\n                      <jats:bold>What is New<\/jats:bold>:\u2022 <jats:italic>There are limited data in the literature about the efficacy and tolerability of DAAs in children with comorbidities.<\/jats:italic>\u2022 <jats:italic>We reported in the current study that DAAs allowed treatment of HCV-infected children with comorbidities with high SVR and excellent safety profile. These patients should be offered treatment with oral DAAs to help decrease the infectious pool and hence reach the ambitious final goal of global eradication.<\/jats:italic>\n                    <\/jats:td>\n                  <\/jats:tr>\n                <\/jats:tbody>\n              <\/jats:table>\n            <\/jats:table-wrap>\n          <\/jats:p>","DOI":"10.1007\/s00431-025-06038-3","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T07:46:30Z","timestamp":1741592790000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The challenge of treating hepatitis C virus infection in children with comorbidities"],"prefix":"10.1007","volume":"184","author":[{"given":"Engy Adel","family":"Mogahed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nevian","family":"Nabil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haytham","family":"Ghita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afaf","family":"Enayet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa","family":"El-Karaksy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,10]]},"reference":[{"key":"6038_CR1","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/S2468-1253(19)30385-1","volume":"5","author":"J Schmelzer","year":"2020","unstructured":"Schmelzer J, Dugan E, Blach S, Coleman S, Cai Z, DePaola M et al (2020) Global prevalence of hepatitis C virus in children in 2018: a modelling study. 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