Systematic Review With Meta-analysis

Systematic Review With Meta-analysis: The Efficacy and Safety of Direct-acting Antivirals in Children and Adolescents With Chronic Hepatitis C Virus Infection

Giuseppe Indolfi; Sabrina Giometto; Daniele Serranti; Alessandra Bettiol; Elisabetta Bigagli; Salvatore De Masi; Ersilia Lucenteforte

Disclosures

Aliment Pharmacol Ther. 2020;52(7):1125-1133. 

In This Article

Abstract and Introduction

Abstract

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 infection.

Methods: We performed a systematic review and meta-analysis of prospective studies on the efficacy and safety of DAAs in subjects <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 in subjects receiving all doses of treatment and proportion of adverse events in 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 children with cirrhosis (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.

Introduction

The global estimate for hepatitis C virus (HCV) viraemic prevalence in the paediatric population aged 0–18 years was 0.13% (95% confidence interval, 0.08–0.16), corresponding to 3.26 million (2.07–3.9) children with HCV in 2018.[1] The efficacy of direct-acting anti-virals (DAAs) for treatment of HCV infection has been well established in adults. However, there has been a significant delay in the development and access to these treatments for children and adolescents and there remains a paucity of evidence.[2] The US Food and Drug Administration and the European Medicines Agency have recently approved the use of glecaprevir/pibrentasvir for the treatment of HCV in adolescents (12–17 years of age) and of sofosbuvir/ledipasvir and sofosbuvir plus ribavirin for use in children between 3 and 11 years of age. The evidence to support such approvals has come from open-label single arm clinical trials.[3–8] Comparable to the studies that have been conducted in adults, these trials showed that the combinations of DAAs have a high efficacy and an optimal safety profile but have been performed on a limited number of patients. Thus far, no comprehensive meta-analysis of clinical data, examining DAA use in children and adolescents has been conducted. This study utilised meta-analytic techniques to evaluate the efficacy and safety of these treatment combinations in children and adolescents with chronic HCV. Specifically, this study examined the effect of the different available DAA combinations in terms of sustained virologic response at post-treatment week 12 together with the commonly reported safety outcome such as adverse events.

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