PMID- 38293756 OWN - NLM STAT- MEDLINE DCOM- 20240301 LR - 20240301 IS - 1478-3231 (Electronic) IS - 1478-3223 (Linking) VI - 44 IP - 3 DP - 2024 Mar TI - Efficacy and safety of DAA in children and adolescents with chronic HCV infection: A systematic review and meta-analysis. PG - 663-681 LID - 10.1111/liv.15827 [doi] AB - BACKGROUND AND AIMS: We evaluated the effectiveness and safety of pan-genotypic regimens, glecaprevir/pibrentasvir (GLE/PIB), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/daclatasvir (SOF/DCV) and other direct-acting antivirals (DAA) regimens for the treatment of hepatitis C virus (HCV)-infected adolescents (12-18 years), older children (6-11 years), and young children (3-5 years). The purpose of this systematic review and meta-analysis was to inform the World Health Organization (WHO) guidelines. METHODS: We included clinical trials and observational studies published up to August 11, 2021, that evaluated DAA regimens in HCV-infected adolescents, older children, and young children. We searched MEDLINE, EMBASE, and CENTRAL databases and key conference abstracts. Sustained virological response 12 weeks after the end of treatment (SVR12), adverse events (AEs), and treatment discontinuation were the outcomes evaluated. Risk of bias was assessed using a modified version of the ROBINS-I tool. Data were pooled using random-effects models, and certainty of the evidence was assessed using the GRADE approach. RESULTS: A total of 49 studies including 1882 adolescents, 436 older children, and 166 young children were considered. The SVR12 was 100% (95% Confidence Interval: 96-100), 96% (90-100), and 96% (83-100) for GLE/PIB in adolescents, older, and young children, respectively; 95% (90-99), 93% (86-98), and 83% (70-93), for SOF/VEL, respectively; and 100% (97-100) and 100% (94-100) for SOF/DCV in adolescent and older children, respectively. There was a clear trend towards a higher rate of any reported AE from adolescents (50%), older children (53%), to young children (72%). Serious AEs and treatment discontinuations were uncommon in adolescents and older children (<1%) but slightly higher in young children (3%). CONCLUSIONS: All three pan-genotypic DAA regimens were highly effective and well-tolerated and are now recommended by the WHO for use in adults, adolescents, and children down to 3 years, which will simplify procurement and supply chain management. The evidence was based largely on single-arm non-randomized controlled studies. Moreover, there were also missing data regarding key variables such as route of HCV acquisition, presence or absence of cirrhosis, or HIV co-infection that precluded evaluation of the impact of these factors on outcomes. PROSPERO RECORD: CRD42020146752. CI - (c) 2024 The Authors. Liver International published by John Wiley & Sons Ltd. FAU - Indolfi, Giuseppe AU - Indolfi G AUID- ORCID: 0000-0003-3830-9823 AD - Department Neurofarba, University of Florence, Florence, Italy. AD - Paediatric and Liver Unit, Meyer Children's Hospital IRCCS, Firenze, Italy. FAU - Easterbrook, Philippa AU - Easterbrook P AUID- ORCID: 0000-0002-2603-5418 AD - Global HIV, Hepatitis and STI Programmes, World Health Organization Headquarters, Geneva, Switzerland. FAU - Giometto, Sabrina AU - Giometto S AUID- ORCID: 0000-0002-3409-1778 AD - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. FAU - Malik, Farihah AU - Malik F AUID- ORCID: 0000-0003-2752-5926 AD - Great Ormond Street Institute of Child Health, University College London, London, UK. FAU - Chou, Roger AU - Chou R AUID- ORCID: 0000-0001-9269-4051 AD - Departments of Medicine, and Medical Informatics & Clinical Epidemiology, Oregon Health Sciences University, Portland, Oregon, USA. FAU - Lucenteforte, Ersilia AU - Lucenteforte E AUID- ORCID: 0000-0001-5608-5902 AD - Department of Statistics, Computer Science and Applications <>, University of Florence, Florence, Italy. LA - eng GR - 001/WHO_/World Health Organization/International GR - WHO_/World Health Organization/International PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20240131 PL - United States TA - Liver Int JT - Liver international : official journal of the International Association for the Study of the Liver JID - 101160857 RN - WJ6CA3ZU8B (Sofosbuvir) RN - 0 (Antiviral Agents) RN - LI2427F9CI (daclatasvir) RN - 0 (Carbamates) RN - 0 (Imidazoles) RN - 0 (Pyrrolidines) RN - HG18B9YRS7 (Valine) SB - IM MH - Adult MH - Child MH - Adolescent MH - Humans MH - Child, Preschool MH - Sofosbuvir/therapeutic use MH - *Hepatitis C, Chronic/drug therapy MH - Antiviral Agents/adverse effects MH - *Hepatitis C/drug therapy MH - Sustained Virologic Response MH - Hepacivirus MH - Drug Therapy, Combination MH - Genotype MH - Treatment Outcome MH - *Carbamates MH - *Imidazoles MH - *Pyrrolidines MH - Valine/*analogs & derivatives OTO - NOTNLM OT - HCV OT - SVR12 OT - children OT - direct-acting antivirals OT - meta-analysis OT - systematic review EDAT- 2024/01/31 06:42 MHDA- 2024/03/01 06:43 CRDT- 2024/01/31 04:37 PHST- 2023/10/13 00:00 [revised] PHST- 2023/07/17 00:00 [received] PHST- 2023/12/18 00:00 [accepted] PHST- 2024/03/01 06:43 [medline] PHST- 2024/01/31 06:42 [pubmed] PHST- 2024/01/31 04:37 [entrez] AID - 10.1111/liv.15827 [doi] PST - ppublish SO - Liver Int. 2024 Mar;44(3):663-681. doi: 10.1111/liv.15827. Epub 2024 Jan 31.