State of the Art HCV Treatment in Children

  • Christine K. LeeEmail author
  • Maureen M. Jonas
Hepatitis C (H Vargas and S Flamm, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Hepatitis C


Purpose of Review

Hepatitis C infection is a global issue with an estimated 5 million children with active HCV infection worldwide. The advent of oral direct-acting antiviral (DAA) regimens has revolutionized treatment in adults with excellent efficacy and tolerability. There are limited data and few approved therapies in children. The aim of this review is to discuss the currently approved regimens for children and the recently reported results of clinical trials of DAA in children.

Recent Findings

DAA regimens are currently approved only for children ≥ 12 years. For most children < 12 years, it is recommended that HCV therapy be deferred until patients are eligible for oral DAA therapies. For treatment-naïve adolescents with HCV genotype 1, 4, 5, or 6, treatment with ledipasvir/sofosbuvir for 12 weeks has been reported to have sustained virologic response at 12 weeks of 98%. For treatment-naïve adolescents with genotype 2 or 3 HCV, sofosbuvir- ribavirin combination therapy (12 weeks for genotype 2 and 24 weeks for genotype 3) has been reported to have SVR12 of 100% and 97%, respectively. There are promising, recently published studies showing excellent SVR12 rates for ombitasvir/paritaprevir/ritonavir ± dasabuvir ± ribavirin in adolescents with HCV genotype 1 or 4, and sofosbuvir/daclatasvir in children/adolescents with HCV genotype 4. Finally, ledipasvir/sofosbuvir ± ribavirin for children age 6–12 years with genotypes 1, 3, 4, 5, and 6 treated for either 12 or 24 weeks is reported to have an SVR12 rate of 99%.


HCV treatment in children is rapidly evolving. There are now highly effective all-oral, interferon-free regimens for children ≥ 12 years. Clinical trials are on-going for adolescents and children < 12 years with a variety of pangenotypic ribavirin-free regimens, with anticipated approvals in the near future.


Pediatric Children Hepatitis C HCV Treatment Direct-acting antiviral 


Compliance with Ethical Standards

Conflict of Interest

Maureen M. Jonas reports grants from Gilead Sciences, grants from AbbVie, grants from Merck, grants from Bristol Myers-Squibb, grants from Roche, and personal fees from Gilead Sciences, outside the submitted work. Christine K. Lee received research support in the form of transient elastography hardware from Echosens; no other support was given.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014;61:S45–57.CrossRefGoogle Scholar
  2. 2.
    Alter MJ, Kruszon-Moran D, Nainan OV, McQuillan GM, Gao F, Moyer LA, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341:556–62.CrossRefGoogle Scholar
  3. 3.
    Jhaveri R. Diagnosis and management of hepatitis C virus-infected children. Pediatr Infect Dis J. 2011;30:983–5.CrossRefGoogle Scholar
  4. 4.
    Denniston MM, Jiles RB, Drobeniuc J, Klevens RM, Ward JW, McQuillan GM, et al. Chronic hepatitis C virus infection in the United States, National Health and Nutrition Examination Survey 2003 to 2010. Ann Intern Med. 2014;160:293.CrossRefGoogle Scholar
  5. 5.
    Conte D, Fraquelli M, Prati D, Colucci A, Minola E. Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women. Hepatology. 2000;31:751–5.CrossRefGoogle Scholar
  6. 6.
    Suryaprasad AG, White JZ, Xu F, Eichler BA, Hamilton J, Patel A, et al. Emerging epidemic of hepatitis C virus infections among young nonurban persons who inject drugs in the United States, 2006-2012. Clin Infect Dis. 2014;59:1411–9.CrossRefGoogle Scholar
  7. 7.
    Minola E, Prati D, Suter F, Maggiolo F, Caprioli F, Sonzogni A, et al. Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C. Blood. 2002;99:4588–91.CrossRefGoogle Scholar
  8. 8.
    Casiraghi MA, De Paschale M, Romanò L, Biffi R, Assi A, Binelli G, et al. Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth. Hepatology. 2004;39:90–6.CrossRefGoogle Scholar
  9. 9.
    Matsuoka S, Tatara K, Hayabuchi Y, Taguchi Y, Mori K, Honda H, et al. Serologic, virologic, and histologic characteristics of chronic phase hepatitis C virus disease in children infected by transfusion. Pediatrics. 1994;94:919.Google Scholar
  10. 10.
    Vogt M, Lang T, Frösner G, Klingler C, Sendl AF, Zeller A, et al. Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening. N Engl J Med. 1999;341:866–70.CrossRefGoogle Scholar
  11. 11.
    Tovo PA, Pembrey LJ, Newell ML. Persistence rate and progression of vertically acquired hepatitis C infection. European Paediatric hepatitis C virus infection. J Infect Dis. 2000;181:419.CrossRefGoogle Scholar
  12. 12.
    Mohan P, Colvin C, Glymph C, Chandra RR, Kleiner DE, Patel KM, et al. Clinical spectrum and histopathologic features of chronic hepatitis C infection in children. J Pediatr. 2007;150:168–174.e1.CrossRefGoogle Scholar
  13. 13.
    Matsuoka S, Tatara K, Hayabuchi Y, Nii M, Mori K, Kuroda Y. Post-transfusion chronic hepatitis C in children. J Paediatr Child Health. 1994;30:544–6.CrossRefGoogle Scholar
  14. 14.
    Lee CK, Perez-Atayde AR, Mitchell PD, Raza R, Afhdal NH, Jonas MM. Serum biomarkers and transient elastography as predictors of advanced liver fibrosis in a United States cohort: The Boston Children’s Hospital Experience. J Pediatr. 2013;163(4):1058–64.CrossRefGoogle Scholar
  15. 15.
    Lee CK, Mitchell PD, Raza R, Harney S, Wiggins SM, Jonas MM. Validation of transient elastography cut points to assess advanced liver fibrosis in children and young adults: The Boston Children’s Hospital Experience. J Peds. 2018;198:84–89.e2. Scholar
  16. 16.
    Goodman ZD, Makhlouf HR, Liu L, Balistreri W, Gonzalez-Peralta RP, Haber B, et al. Pathology of chronic hepatitis C in children: liver biopsy findings in the Peds-C trial. Hepatology. 2008;47:836–43.CrossRefGoogle Scholar
  17. 17.
    González-Peralta RP, Langham MR Jr, Andres JM, Mohan P, Colombani PM, Alford MK, et al. Hepatocellular carcinoma in 2 young adolescents with chronic hepatitis C. J Pediatr Gastroenterol Nutr. 2009;48:630–5.CrossRefGoogle Scholar
  18. 18.
    Strickland DK, Riely CA, Patrick CC, Jones-Wallace D, Boyett JM, Waters B, et al. Hepatitis C infection among survivors of childhood cancer. Blood. 2000;95:3065.Google Scholar
  19. 19.
    •• American Association for the Study of Liver Diseases: HCV guidance: Recommendations for testing, managing, and treating hepatitis C. Available at: This is the consensus recommendation of the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA). They include evidence-based, expert-developed recommendations for hepatitis C management which are updated on a regular basis as new information becomes available.
  20. 20.
    Jonas MM. Hepatitis C virus infection in children. In: UpToDate Post TW (Ed), UpToDate, Waltham, MA (Accessed on 12/15/2018.) Copyright © 2018 UpToDate, Inc., 2013.
  21. 21.
    • Balistreri WF, Murray KF, Rosenthal P, Bansal S, Lin CH, Kersey K, et al. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12-17 years old with hepatitis C virus genotype 1 infection. Hepatology. 2017;66:371. This study reviews the results of a phase 2, multicenter open-label trial of ledipasvir-sofosbuvir for 12 weeks in adolescents with genotype 1. The regimen was safe, well tolerated and had similar pharmacokinetics to adult reports.–8.CrossRefGoogle Scholar
  22. 22.
    Leung DH, Wirth S, Yao BB, Viani RM, Gonzalez-Peralta RP, Jonas MM, et al. Ombitasvir/partiaprevir/ritonavir with or without dasabuvir and with or without ribavirin for adolescents with HCV genotype 1 or 4. Hepatol Commun. 2018;2(11):1311–9.CrossRefGoogle Scholar
  23. 23.
    El-Khayat HR, Kamal EM, El-Sayed MH, El-Shabrawi M, Ayoub H, Rizk A, 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;47:838–44.CrossRefGoogle Scholar
  24. 24.
    El-Karaksy H, Mogahed EA, Abdullatif H, Ghobrial C, El-Raziky MS, El-Koofy N, 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
  25. 25.
    Abdel Ghaffar TY, Naghi SE, Gawad MA, Helmy S, Ghaffar AA, Yousef M, et al. Safety and efficacy of combined sofosbuvir/daclatasvir treatment of children and adolescents with chronic hepatitis genotype 4. J Viral Hepat. 2018;26:263–70. Scholar
  26. 26.
    • Wirth S, Rosenthal P, Gonzalez-Peralta RP, Jonas MM, Balistreri WF, Lin CH, et al. Sofosbuvir and ribavirin in adolescents 12-17 years old with hepatitis C virus genotype 2 or 3 infection. Hepatology. 2017;66:1102 This study reports the results of combination sofosbuvir and ribavirin treatment for 12 weeks in those with genotype 2 and 24 weeks in genotype 3 patients. The regiment was safe, well tolerated with pharmacokinetics similar to adults. CrossRefGoogle Scholar
  27. 27.
    Murray KF, Balistreri WF, Bansal S, Whitworth S, Evans HM, Gonzalez-Peralta RP, et al. Safety and efficacy of ledipasvir-sofosbuvir with or without ribavirin for chronic hepatitis c in children ages 6-11. Hepatology. 2018;68(6):2158–66.CrossRefGoogle Scholar
  28. 28.
    Jonas MM, Squires RH, Rhee SM, Lin CW, Bessho K, et al. Pharmacokinetics, safety and efficacy of glecaprevir/pibrentasvir in pediatric patients with genotypes 1-6 chronic HCV infection: part 1 of the DORA study. Hepatology. 2018;68(S1):1347A–8A.Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Gastroenterology, Hepatology and NutritionBoston Children’s HospitalBostonUSA

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