https://pubmed.ncbi.nlm.nih.gov/40113366/ Hepatitis C
Observational Study

Lancet Child Adolesc Health. 2025 Apr;9(4):248-254.
doi: 10.1016/S2352-4642(25)00028-8.

Long-term efficacy and safety of sofosbuvir-based direct-acting antiviral regimens in paediatric patients with hepatitis C virus infection: an international registry study

Regino P Gonzalez-Peralta 1, Jessica W Wen 2, Winita Hardikar 3, Wikrom W Karnsakul 4, Suzanne Whitworth 5, Chuan-Hao Lin 6, Giuseppe Indolfi 7, Philip Rosenthal 8, William Balistreri 9, Kathleen B Schwarz 4, Jonathan R Honegger 10, Xu Zhang 11, Evguenia C Svarovskaia 11, Vithika Suri 11, Kathryn Kersey 11, Daniel H Leung 12
Affiliations expand
PMID: 40113366

DOI: 10.1016/S2352-4642(25)00028-8
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Abstract

Background: Direct-acting antiviral treatment is associated with high rates of sustained virological response and has a favourable safety profile in children aged 3-17 years with chronic hepatitis C virus (HCV) infection, but data describing the durability of sustained virological response and its effects on growth and sexual development are needed. This study aimed to assess the efficacy and long-term effects of sofosbuvir-based direct-acting antiviral regimens on growth and development in the paediatric population.

Methods: In this international, multicentre, observational registry study, children aged 3-17 years with HCV who received sofosbuvir plus ribavirin, ledipasvir plus sofosbuvir with or without ribavirin, sofosbuvir plus velpatasvir, or sofosbuvir plus velpatasvir plus voxilaprevir in previous clinical trials were eligible for follow-up of growth and sexual development parameters for up to 5 years. Registry baseline was documented as the last follow-up visit under the parent study protocol and follow-up consisted of clinical visits every 6 months for the first 2 years and every 12 months thereafter for up to 5 years, during which symptom-directed physical examination, height and weight measurements, Tanner pubertal stage assessment, procedure-related adverse events documentation, and blood sampling collection were completed. The primary endpoints were changes, relative to baseline, in height, weight, BMI Z scores, and Tanner pubertal stage. Height, weight, BMI, and corresponding percentiles and Z scores were summarised using descriptive statistics. The study was registered at ClinicalTrials.gov (NCT02510300).

Findings: Between October 2015 and June 2021, 461 participants were enrolled in the registry. 426 (92%) participants had at least one post-baseline assessment and were included in the analysis. 93 (20%) participants were previously treated with sofosbuvir plus ribavirin, 192 (42%) with ledipasvir plus sofosbuvir with or without ribavirin, 158 (34%) with sofosbuvir plus velpatasvir, and 18 (4%) with sofosbuvir plus velpatasvir plus voxilaprevir. Most participants included in the analysis were female (247 [58%] participants; sex assigned at birth) and White (342 [80%] participants). The most common HCV genotypes were GT1 (281 [66%] participants) and GT3 (88 [21%] participants). Clinical assessments continued until January 2023. The median follow-up was 3·7 years (IQR 2·7-4·6) among the 426 participants, 302 (71%) of whom completed at least 3 years of follow-up. 424 (>99%) of 426 participants had previously achieved sustained virological response during their parent studies. With a mean age of 12 years (SD 4·1) at baseline, the median change in median Z scores during follow-up was 0·0 (IQR -0·2 to 0·4) for height, 0·1 (-0·3 to 0·5) for weight, and 0·0 (-0·3 to 0·5) for BMI. Increases in Tanner stage were consistent with age, regardless of sex or which secondary sexual characteristic was assessed.

Interpretation: No change in growth or sexual development was detected during prolonged follow-up of paediatric patients who had completed treatment with sofosbuvir-based direct-acting antivirals for chronic HCV. Prolonged clinical follow-up of children who have achieved sustained virological response might not be necessary.