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Direct-acting antivirals (DAAs) have transformed the management of Hepatitis C Virus (HCV) infection, offering highly effective, short-duration, and well-tolerated treatment options. 1 This study evaluates the safety, efficacy, and treatment outcomes of DAAs in a paediatric population.We conducted a retrospective analysis of 49 paediatric patients with chronic HCV infection treated at our centre between August 2017 and December 2024. Patient demographics, biochemical parameters, genotype (G) distribution, treatment regimens, and sustained virologic response at 12 weeks (SVR12) were analyzed.Baseline investigations included liver function tests, full blood count, renal function, alpha-fetoprotein, abdominal ultrasound, Fibroscan, Liver biopsy when available, virology screening for Hepatitis B, Hepatitis A and Human Immunodeficiency Virus. HCV RNA (Ribonucleic acid) quantitative Polymerase chain reaction (PCR) monitoring occurred at weeks 4, 8, and/or 12 after starting DAA. The choice of DAA was guided by the Operational Delivery Network (ODN) set up in the United Kingdom for paediatric HCV infection. The results are summarised in table 1.The treatment was genotype specific. G3 (n=22) and G2a(n=1) received 12 weeks of with Sofosbuvir/Velpatasvir (SOF/VEL) or 8 weeks of Glecaprevir/Pibrentasvir (GLE/PIB). G1a (n=17), G1b (n=3), combined G1a/1b (n=3), and G4 (n=3) received sofosbuvir/ledipasvir (SOF/LDV) for 8 or 12 weeks according to protocol. HCV was acquired as vertical transmission in 46 children (93.8%). None had HBV or HIV co-infection; four had past hepatitis A infection. Three patients were treatment-experienced before DAA, two with pegylated interferon/ribavirin (RBV) and one with telaprevir/RBV and were non-responders or discontinued due to adverse effects.Two treatment-naïve patients (4.1%) developed primary resistance to SOF/LDV (one G1a, one G1b). Both achieved sustained virologic response after retreatment with alternative regimes—one with GLE/PIB and the other with extended SOF + GLE/PIB + RBV.Overall, 47/49 patients (95.9%) achieved SVR12 after the primary course, and all after extended therapy or retreatment of the nonresponders with alternative regime. Children who reached 1-year post DAA (n=46), 43 maintained undetectable HCV RNA and results were not available in 3. No hepatic, renal, or haematological toxicity occurred.DAA therapy was highly effective and well-tolerated in paediatric HCV patients. Resistance testing and access to multiple DAA regimens remain essential for optimizing outcomes in this population.Reference HCV Guidance: Recommendations for Testing, Managing and Treating Hepatitis C 2014-2023 AASLD and IDSA v2023. 1Abstract OC17 Table 1Patient demographics, treatment characteristics, and outcomes for paediatric HCV infection