Effects of Sofosbuvir/Ledipasvir Therapy on Chronic Hepatitis C Virus Genotype 4, Infected Children of 3–6 Years of Age

Enas M. Kamal; Mortada El-Shabrawi; Hisham El-Khayat; Mostafa Yakoot; Yehia Sameh; Yasser Fouad; Dina Attia


Liver International. 2020;40(2):319-323. 

In This Article

Abstract and Introduction


Background & Aims: Treatment of children aged 3–6 genotype 4 is still limited by the interferon side effects. We aimed in this study to evaluate the effectiveness and safety of sofosbuvir/ledipasvir in children (3–6 years) genotype 4 chronic HCV-infected patients.

Methods: In total, 22 consecutive chronic HCV-infected patients (mean age 4.8 ± 0.9years, 19 males) were included in this prospective study. All patients received sofosbuvir 200 mg/ledipasvir 45 mg in a single oral daily dose. Patients were randomly subdivided into two groups according the duration of treatment into 8 and 12 weeks. All the clinical and laboratory data were collected. All the side effects were recorded from the patients or their parents. Follow-up were made at Week 4, 8 and 12 and 12 weeks after the end of treatment (SVR12).

Results: The overall SVR12 rate was 100%. At Week 4, 9/11 patients in the 12-week group (81.8%; 95% CI: 52.3%-94.7%) achieved virologic negativity, vs 10/11 (90.9%; 95% CI: 62.3%-98.4%) in the 8-week group. At Week 8, 10/11 (90.8%; 95% CI: 62.3%-98.4%) in the 12-week group vs 11/11 (100%; 95% CI: 74.1%-100%) in the 8-week group were virologically negative. The reported side effects were cough, abdominal pain, nausea, vomiting and diarrhoea especially early in the treatment. The main complaint was difficulty in swallowing the tablets in the youngest patient at the beginning of the course of treatment. All patients were compliant to treatment.

Conclusion: Sofosbuvir/ledipasvir combination is safe and tolerable in the chronic infected HCV genotype 4 infected children (3–6 years). The 8-week treatment duration is similarly effective as the 12-week duration.


Chronic hepatitis C virus (HCV) infection represents a worldwide health burden.[1–4] The estimated rate of chronic infection in children younger than 15 years old is 2.1–5 million worldwide.[2,5,6] Egypt has one of the highest prevalence rates for HCV infection worldwide.[7] The prevalence specifically in children is similarly high, at 5.8%–6% in comparison to 0.05%–0.36% in the USA and Europe.[8–10] Vertical transmission by way of perinatal infection represents the main mode of infection in Egypt.[7,11] Infants infected via the vertical transmission route show spontaneous resolution in around 25% cases by the age of 3 years.[12] The progression to chronic liver disease and the development of HCC is uncommon in children and adolescents, yet slow progression can occur and is associated with high morbidity and mortality rates among untreated cases.[13] Treating children and adolescents is therefore of need to avoid progression of liver disease and disease transmission.[13] Until recently, the only approved treatment was the pegylated interferon/ribavirin regimen for 24 weeks, which promoted only a limited response in genotypes 1 and 4 (<30% and 61%, respectively), and the development of serious associated side effects of treatment with this medication including drug discontinuation and anaemia has largely discouraged its use in the children and adolescent populations.[14–17] Direct-acting antiviral (DAA) regimens were approved in 2013 with an excellent response rate of more than 95% and minimal side effects for 12 weeks. Moreover, the availability and the lower cost offered by the government allowed for mass screening and treatment in Egypt. Separately, the combination of sofosbuvir and ledipasvir has shown a response rate exceeding 95% with minimal side effects in adults.[11] The United States Food and Drug Administration (FDA) approved this regimen for application in adolescents aged 12–18 years with genotype 4 in 2017, which represents a major step towards avoiding disease progression to chronic liver disease or HCC as well as the transmission of infection.[18] Another study showed this combination is safe and effective in the age group of 6–11 years.[19] Treatment in children aged between 3- and 6 years remains controversial, however, as the incidence of progression to chronic liver disease is not known, while, on the other hand, infection transmission still exists. The availability, affordability and minimal adverse effects that appeared in the older age group encourage the need to identify a cure for use in the 3- to 6-year-old groups. Also, the mass screening programme provided by the government and the awareness of parents in detecting infected children have made it also possible to better locate affected patients. Recently, the FDA approved the sofosbuvir/ledipasvir combination for children aged 3 years with genotypes 1 and 4. Although Schwarz et al investigated this combination in genotype 1 (n = 33); however, genotype 4 was represented only in their study by one patient.[20] Therefore, the aim of our study was to evaluate the safety and effectiveness of the sofosbuvir/ledipasvir combination in children (3–6 years) with genotype 4 chronic HCV infection.