Systematic review with meta-analysis: the efficacy and safety of direct-acting antivirals in children and adolescents with chronic hepatitis C virus infection

Background The effect of direct-acting anti-virals (DAAs) in children and adolescents with chronic hepatitis C virus (HCV) infection is difficult to determine, since few, aged between 3 and 18 years, have been enrolled in clinical trials, and some data come from observational studies. Aim To summarise the evidence on efficacy and safety of DAAs in children and adolescents with chronic HCV. Methods We performed a systematic review and a meta-analysis of prospective studies on the efficacy and safety of DAAs in subjects with <18 years of age. We considered the sustained virological response at post-treatment week 12 as efficacy outcome and adverse events as safety outcome. We considered intervention effect for each study arm by calculating the proportion of sustained virologic response at post-treatment week 12 on subjects receiving all doses of treatment and proportion of adverse events on subjects receiving at least one dose of treatment. Pooled proportions were calculated using the Freeman-Tukey double arcsine transformation. Random effects model was used for all analyses. Results Among 39 included studies (1796 subjects), the pooled proportion among those receiving all doses of treatment and reaching sustained virologic response at post-treatment week 12 was 100% (95% confidence interval: 100-100). Considering subjects receiving at least one dose of treatment, lowest estimates were reported among cirrhotic children (83%). Headache and fatigue were the most common adverse events. Serious adverse events were uncommon. Conclusions Children and adolescents with chronic HCV infection can be safely treated with DAAs with similar efficacy as reported in adults.