Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and children with hepatitis C

Abstract

Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%–2% of the pediatric population in the United States. While the clinical course in young children is indolent, adolescents who contract HCV have a disease course similar to adults, with a 26-fold increased risk of chronic liver disease-associated mortality, hepatocellular carcinoma, and need for curative liver transplantation. Furthermore, adolescent patients are entering childbearing age and carry a risk of passing HCV to their offspring via vertical transmission. Pegylated-interferon (PEG-IFN) with ribavirin was previously the only treatment option for pediatric patients with chronic hepatitis C (CHC), but the high likelihood of adverse reactions and subcutaneous route of administration limited its use and efficacy. Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir (SOF) were approved for adolescents with CHC. This review discusses the natural history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and ongoing studies evaluating DAAs in pediatric patients.

Clinical, Virological Characteristics, and Outcomes of Treatment with Sofosbuvir/Ledipasvir in Two Pediatric Patients Infected by HCV Genotype 4

“…Since an effective treatment is now available, it is important to diagnose and treat all children who are chronically infected by HCV. First, for adolescent patients and children, the SOF/LDV combination allows to achieve SVR rates of 98% [7,22]. Moreover, an ongoing Phase II, multicenter open-label trial (NCT 02249182) reported no serious adverse events in HCV1-infected patients during treatment [23].…”

“…More studies are necessary to explore whether the presence of these variants correlates with treatment failure in children. To the best of our knowledge, the ongoing clinical trials including adolescent aged 12–17 years are evaluating efficacy and safety of treatment, including adverse events [7].…”

“…Prescription criteria are based on age (children older than 12 years) and weight (children exceeding 35 kg) [6]. Clinical trials in younger children are ongoing; however, preliminary data showed a good safety and efficacy of SOF/LDV in adolescents with an SVR rate of 98% [7]. Pangenotypic regimens are currently under study in children but are not yet approved by FDA [5].…”