Generic sofosbuvir/ledipasvir for the treatment of genotype 4 chronic hepatitis C in Egyptian children (9–12 years) and adolescents

  • Hanaa A. El-Araby
  • Behairy E. Behairy
  • Mohamed A. El-Guindi
  • Nermin M. Adawy
  • Alif A. Allam
  • Ahmad M. SiraEmail author
  • Mohamed A. Khedr
  • Ibrahim A. Elhenawy
  • Gihan A. Sobhy
  • Hosam El Din M. Basiouny
  • Menan E. Salem
  • Samira A. Abdel-Aziz
  • Ola A. Fouad
  • Bassam A. Ayoub
Original Article


Background/purpose of the study

Worldwide and national efforts are directed against eradication of HCV. The introduction of direct-acting antivirals (DAAs) has changed dramatically the outcome of HCV treatment. In spite of the Food and Drug Administration approval of the oral drugs sofosbuvir (SOF) and ledipasvir (LED) for the treatment of HCV in adolescents more than or equal to 12 years old, sufficient real-world experience is still lacking. The aim of this study was to assess the safety and efficacy of the generic SOF/LED fixed-dose combination 400/90 (400 mg SOF + 90 mg LED) for the treatment of adolescents and children (9–12 years) with chronic hepatitis C (CHC).


In this prospective observational study, 100 cases of genotype 4 CHC were recruited consecutively from those fulfilling the inclusion and exclusion criteria. All cases received the generic fixed-dose combination SOF/LED (400/90), one tablet daily for 12 weeks. All clinical, laboratory, and virologic characteristics were evaluated at base line, and week (W) 2, 4, 8, and 12 of therapy and W12 post-treatment (SVR12).


Recruited children (9–12) and adolescents weighed 28–83 and 31–90 kg, respectively. Eighty cases were naïve and 20 cases were pegylated interferon/ribavirin treatment-experienced. Very rapid virologic response (vRVR) at W2 was 96%, while at W4 response rate was 100% and maintained till the end of treatment and at W12 post-treatment (SVR12). All reported side effects were mild and did not lead to treatment termination and disappeared at W12 post-treatment.


The generic SOF/LED fixed-dose combination is safe and effective in children, 9–12 years, and adolescents with vRVR rate of 96%, 100% EOT response and SVR12.


Children Hepatitis C virus Ledipasvir Sofosbuvir 



We acknowledge National Liver Institute, Menofiya University, for funding this work. We would like to thank the residents and nursing staff of the Pediatric Hepatology, Gastroenterology, and Nutrition Department and all physicians and working staff of the Clinical Biochemistry and Radiology Departments for their contribution.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The study was approved by the Research Ethics Committee of the National Liver Institute, Menofiya University and conforms to the 1964 Declaration of Helsinki and its later amendments. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent

Informed consent was obtained from parents/guardians of all patients for being included in the study.


  1. 1.
    Guerra J, Garenne M, Mohamed MK, et al. HCV burden of infection in Egypt: results from a nationwide survey. J Viral Hepat 2012;19(8):560–567.CrossRefGoogle Scholar
  2. 2.
    Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014;61(1 Suppl):S45–S57.CrossRefGoogle Scholar
  3. 3.
    El-Karaksy H, Anwar GH, El-Raziky MS, et al. Anti-HCV prevalence among diabetic and non-diabetic Egyptian children. Curr Diabetes Rev 2010;6(6):388–392.CrossRefGoogle Scholar
  4. 4.
    Barakat SH, El-Bashir N. Hepatitis C virus infection among healthy Egyptian children: prevalence and risk factors. J Viral Hepat 2011;18(11):779–784.CrossRefGoogle Scholar
  5. 5.
    El-Raziky MS, El-Hawary M, Esmat G, et al. Prevalence and risk factors of asymptomatic hepatitis C virus infection in Egyptian children. World J Gastroenterol 2007;13(12):1828–1832.CrossRefGoogle Scholar
  6. 6.
    Chaabna K, Cheema S, Abraham A, et al. Systematic overview of hepatitis C infection in the Middle East and North Africa. World J Gastroenterol 2018;24(27):3038–3054.CrossRefGoogle Scholar
  7. 7.
    Denniston MM, Jiles RB, Drobeniuc J, et al. Chronic hepatitis C virus infection in the United States, National Health and nutrition examination survey 2003–2010. Ann Intern Med 2014;160(5):293–300.CrossRefGoogle Scholar
  8. 8.
    Khaderi S, Shepherd R, Goss JA, et al. Hepatitis C in the pediatric population: transmission, natural history, treatment and liver transplantation. World J Gastroenterol. 2014;20(32):11281–11286.CrossRefGoogle Scholar
  9. 9.
    El-Araby HA, Ehsan NA, Konsowa HA, et al. Hepatic progenitor cells in children with chronic hepatitis C: correlation with histopathology, viremia, and treatment response. Eur J Gastroenterol Hepatol 2015;27(5):561–569.CrossRefGoogle Scholar
  10. 10.
    Gonzalez-Peralta RP, Langham MR Jr, Andres JM, et al. Hepatocellular carcinoma in 2 young adolescents with chronic hepatitis C. J Pediatr Gastroenterol Nutr 2009;48(5):630–635.CrossRefGoogle Scholar
  11. 11.
    Hepatitis C. Guidance 2018 update: AASLD-IDSA Recommendations for testing, managing, and treating hepatitis C virus infection. Clin Infect Dis 2018;67(10):1477–1492.CrossRefGoogle Scholar
  12. 12.
    El Naghi S, Abdel-Ghaffar TY, El-Karaksy H, et al. Safety and efficacy of Hansenula-derived PEGylated-interferon alpha-2a and ribavirin combination in chronic hepatitis C Egyptian children. World J Gastroenterol 2014;20(16):4681–4691.CrossRefGoogle Scholar
  13. 13.
    Kamal SM, Nasser IA. Hepatitis C genotype 4: What we know and what we don’t yet know. Hepatology 2008;47(4):1371–1383.CrossRefGoogle Scholar
  14. 14.
    Abdel-Hamid M, El-Daly M, Molnegren V, et al. Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma. J Gen Virol 2007;88(Pt 5):1526–1531.CrossRefGoogle Scholar
  15. 15.
    El-Karaksy H, Mogahed EA, Abdullatif H, et al. Sustained viral response in genotype 4 chronic hepatitis C virus-infected children and adolescents treated with Sofosbuvir/Ledipasvir. J Pediatr Gastroenterol Nutr. 2018;67(5):626–30.CrossRefGoogle Scholar
  16. 16.
    El-Khayat HR, Kamal EM, El-Sayed MH, et al. The effectiveness and safety of ledipasvir plus sofosbuvir in adolescents with chronic hepatitis C virus genotype 4 infection: a real-world experience. Aliment Pharmacol Ther 2018;47(6):838–844.CrossRefGoogle Scholar
  17. 17.
    Ghobrial C, Sobhy R, Mogahed E, et al. Is sofosbuvir/ledipasvir safe for the hearts of children with hepatitis C virus? Dig Liver Dis 2019;51(2):258–262.CrossRefGoogle Scholar
  18. 18.
    Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 1987;34(3):571–590.CrossRefGoogle Scholar
  19. 19.
    Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology 2008;134(4):960–974.CrossRefGoogle Scholar
  20. 20.
    El-Akel W, El-Sayed MH, El Kassas M, et al. National treatment programme of hepatitis C in Egypt: hepatitis C virus model of care. J Viral Hepat 2017;24(4):262–267.CrossRefGoogle Scholar
  21. 21.
    Squires JE, Balistreri WF. Hepatitis C virus infection in children and adolescents. Hepatol Commun 2017;1(2):87–98.CrossRefGoogle Scholar
  22. 22.
    Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. Geneva: World Health Organization; 2018. p. 1–86. ISBN 978-92-4-155034-5.
  23. 23.
    El-Shabrawi MH, Abdo AM, El-Khayat HR, et al. Shortened 8 weeks course of dual Sofosbuvir/Daclatasvir therapy in adolescent patients, with chronic hepatitis C infection. J Pediatr Gastroenterol Nutr 2018;66(3):425–427.CrossRefGoogle Scholar
  24. 24.
    Balistreri WF, Murray KF, Rosenthal P, et al. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12–17 years old with hepatitis C virus genotype 1 infection. Hepatology 2017;66(2):371–378.CrossRefGoogle Scholar
  25. 25.
    Wirth S, Rosenthal P, Gonzalez-Peralta RP, et al. Sofosbuvir and ribavirin in adolescents 12–17 years old with hepatitis C virus genotype 2 or 3 infection. Hepatology 2017;66(4):1102–1110.CrossRefGoogle Scholar
  26. 26.
    Lemoine M, Eholie S, Lacombe K. Reducing the neglected burden of viral hepatitis in Africa: strategies for a global approach. J Hepatol 2015;62(2):469–476.CrossRefGoogle Scholar
  27. 27.
    Healthcare P. Heterosofir Plus. 2019 [cited 2019 7 January 2019];
  28. 28.
    Halter C. Egypt Could Eliminate Hepatitis C Among Its Population by 2023. 2018 May 29 [cited 2019 August 13].
  29. 29.
    El-Shabrawi MHF, Kamal NM, El-Khayat HR, et al. A pilot single arm observational study of sofosbuvir/ledipasvir (200 + 45 mg) in 6- to 12- year old children. Aliment Pharmacol Ther 2018;47(12):1699–1704.CrossRefGoogle Scholar
  30. 30.
    Shiha G, Esmat G, Hassany M, et al. Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt. Gut 2019;68(4):721–728.CrossRefGoogle Scholar
  31. 31.
    Tao T, Jiang X, Chen Y, et al. Efficacy and safety of Ledipasvir/Sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: a meta-analysis. Int J Infect Dis 2017;55:56–71.CrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  • Hanaa A. El-Araby
    • 1
  • Behairy E. Behairy
    • 1
  • Mohamed A. El-Guindi
    • 1
  • Nermin M. Adawy
    • 1
  • Alif A. Allam
    • 1
  • Ahmad M. Sira
    • 1
    Email author
  • Mohamed A. Khedr
    • 1
  • Ibrahim A. Elhenawy
    • 1
  • Gihan A. Sobhy
    • 1
  • Hosam El Din M. Basiouny
    • 1
  • Menan E. Salem
    • 1
  • Samira A. Abdel-Aziz
    • 1
  • Ola A. Fouad
    • 1
  • Bassam A. Ayoub
    • 1
  1. 1.Department of Pediatric Hepatology, Gastroenterology, and Nutrition, National Liver InstituteMenofiya UniversityMenofiyaEgypt

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