The Challenge of Treating Children With Hepatitis C Virus Infection

Abstract

The development of oral hepatitis C virus (HCV) direct-acting antivirals (DAAs) has revolutionized the therapeutic field. Nowadays, multiple safe and highly effective antiviral regimens are commercially available to treat adults with hepatitis C infection. These new regimens for the first time genuinely raise the prospects of eradicating HCV. Many challenges, however, remain from identifying infected individuals to optimizing treatment and ensuring global access to antiviral therapy to all population groups, including children. Recently, in April 2017, the association of sofosbuvir with ribavirin and the fixed-dose combination sofosbuvir/ledipasvir have been approved by the Food and Drug Administration for treatment of children with chronic HCV infection 12 years of age and older. The only drugs currently approved for children younger than 12 years are pegylated interferon and ribavirin. There are 6 registered ongoing pediatric trials assessing safety and efficacy of DAAs, but their current completion timelines are years away. Herein, we summarize the state of the art of DAAs' development for adult and children and highlight the crucial importance of overcoming barriers to treating children with HCV.

Hepatitis C virus infection in children and adolescents

“…106 It is anticipated that other key DAA studies will be completed in children aged 6 to 11 years during 2018 with anticipated regulatory approval in 2019. 109 The anticipated dates of completion of the trials of ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin (NCT02486406), glecaprevir/pibrentasvir (NCT03067129) and sofosbuvir/velpatasvir (NCT 03022981) trials are September and December 2019, respectively. There is a relatively small number of adolescents and children diagnosed with chronic HCV infection available for recruitment into clinical studies in high income countries, and a need for more pro-active case finding and enrolment also from LMICs to accelerate completion.…”

Hepatitis C virus therapy in children: No one should be left behind

“…Such populations are represented by patients affected by chronic kidney disease who are on haemodialysis, transfusion‐dependent thalassaemic patients, people living with the human immunodeficiency virus, people who use drugs and children . In these particular groups of patients eradication of HCV infection has a multifold perspective: it allows treating all patients with a given condition, or demographical characteristic, in a reasonably limited period of time, drastically reducing the likelihood of further diffusion of infection within the same communities; it portends an added benefit provided by HCV clearance to the therapeutic management of comorbid conditions; and in the paediatric setting it not only improves the projected health benefit in an otherwise healthy population by eliminating the potential for chronic liver disease progression and the development of associated conditions but also frees young patients from the social and psychological stigmata of a transmissible disease …”

Hepatitis C virus infection in children in the era of direct-acting antiviral

“…The development of oral interferon-free (IFN-free) anti-HCV treatment with direct-acting antivirals (DAAs) has revolutionized the therapy of HCV infection. Currently, highly effective, safe and well-tolerated antiviral regimens are available to treat adults with hepatitis C infection[ 34 ].…”

“…Children with HCV genotypes 1 or 4 infection should be treated for 48 wk whereas those infected with genotypes 2 or 3 should be treated for 24 wk[ 20 , 35 - 39 ]. Few data are available on the paediatric use of DAAs, and 7 clinical trials are currently ongoing (NCT 3067129, NCT 2486406, NCT 3080415, NCT 2868242, NCT 2249182, NCT 3022981, NCT 2985281[ 34 , 40 ]) (Table 1 ).…”

“…Although new treatments are expected to be approved for paediatric use for all age groups in the near future, there is uncertainty on the current optimal approach to treat children with chronic HCV infection[ 34 , 54 ]. The Hepatology Committee of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) developed an evidence-based position paper for the management of chronic HCV infection in children.…”