Purpose of Review
The aim of this study is to summarize the state of treatment of hepatitis C virus (HCV) infection in children.
The 100 articles on HCV in children from 2011 to 2016 contained only one report of a trial with direct acting antiviral agents (DAAs) and none of these agents are yet FDA-approved for children. Thus, we will focus on issues critical to the understanding of the problem of HCV in the pediatric age group including global epidemiology and natural history, as well as results of treatment with the only agents currently FDA-approved for pediatric use: pegylated interferon alpha 2a or 2b plus ribavirin. In addition, the pediatric trials with DAAs in progress will be described.
Standard therapy is indicated for some children with HCV but the majority should await approval of DAAs. An algorithm for management and treatment of subjects <18 years of age at the present time is provided.
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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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Chen ST, Ni YH, Chen PJ, Chen HL, Jeng YM, Lu MY, et al. Low viraemia at enrollment in children with chronic hepatitis C favours spontaneous viral clearance. J Viral Hepat. 2009;16:796–801. doi:10.1111/j.1365-2893.2009.01135.x.
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European Paediatric HIVHCV Co-infection Study Group in the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) in EuroCoord. Coinfection with HIV and hepatitis C virus in 229 children and young adults living in Europe. AIDS. 2017;31(1):127–35. doi:10.1097/QAD.0000000000001285. One of the risk factors is HIV/HCV co-infection and this was extensively reported by European Paediatric HIV/HCV study group with progressive liver disease among this vertically acquired HCVinfected children and young adults
Mohan P, Barton BA, Narkewicz MR, Molleston JP, Gonzalez-Peralta RP, Rosenthal P, et al. Evaluating progression of liver disease from repeat liver biopsies in children with chronic hepatitis C: a retrospective study. Hepatology. 2013;58:1580–6. doi:10.1002/hep.26519.
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Roy A, Wang C, Li C, Lu L, Torbenson M, Hagedorn CH, et al. Phenotypic and genotypic differences between a child with vertically acquired severe hepatitis C liver disease and his mother. J Pediatr Gastroenterol Nutr. 2012;54:567–9. doi:10.1097/MPG.0b013e318229d96f.
Abdelaziz DH, Elhosseiny NM, Khaleel SA, Sabry NA, Attia AS, El-Sayed MH. Association between combined presence of hepatitis C virus and polymorphisms in different genes with toxicities of methotrexate and 6-mercaptopurine in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2016;63:1539–45. doi:10.1002/pbc.26045.
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Abu Faddan NH, Shehata GA, Abd Elhafeez HA, Mohamed AO, Hassan HS, et al. Cognitive function and endogenous cytokine levels in children with chronic hepatitis C. J Viral Hepat. 2015;22:665–70. doi:10.1111/jvh.12373.
•• Mack CL, Gonzalez-Peralta RP, Gupta N, Leung D, Narkewicz MR, Roberts EA, et al. NASPGHAN practice guidelines: diagnosis and management of hepatitis C infection in infants, children, and adolescents. J Pediatr Gastroenterol Nutr. 2012;54:838–55. doi:10.1097/MPG.0b013e318258328d. These two papers focus on pediatric aspects of HCV infection in children. The work from Mack et al in 2012 discussed the guideline which details the epidemiology and natural history of HCV infection in children, the diagnostic workup, monitoring and treatment of disease, and provides an update on future treatment options and areas of research
• Druyts E, Thorlund K, Wu P, et al. Efficacy and safety of pegylated interferon alfa-2a or alfa-2b plus ribavirin for the treatment of chronic hepatitis C in children and adolescents: a systematic review and meta-analysis. Clin Infect Dis. 2013;56:961–7. doi:10.1093/cid/cis1031. Despite the promising DAAs regimens, the current cost is high and may not be available for children in developing countries. A systematic review and meta-analysis conducted by Druyts et al indicates effectiveness and safety in treating HCV-infected children with peg-IFN alfa-2a or peg-IFN alfa-2b plus ribavirin
Schwarz KB, Gonzalez-Peralta RP, Murray KF, Molleston JP, Haber BA, Jonas MM, et al. Peds-C Clinical Research Network. The combination of ribavirin and peginterferon is superior to peginterferon and placebo for children and adolescents with chronic hepatitis C. Gastroenterology. 2011;140:450-458.e1. doi: 10.1053/j.gastro.2010.10.047
Jonas MM, Balistreri W, Gonzalez-Peralta RP, Haber B, Lobritto S, Mohan P, et al. Pegylated interferon for chronic hepatitis C in children affects growth and body composition: results from the pediatric study of hepatitis C (PEDS-C) trial. Hepatology. 2012;56:523–31. doi:10.1097/MPG.0b013e318185998f.
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Alqahtani SA, Afdhal N, Zeuzem S, Gordon SC, Mangia A, Kwo P, et al. Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: analysis of phase III ION trials. Hepatology. 2015;62:25–30. doi:10.1002/hep.27890.
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•• Balistreri WF, Murray KF, Rosenthal P, Bansal S, Chuan-Hao L, Kersey K, et al. The safety and effectiveness of ledipasvir-sofosbuvir in adolescents 12 to 17 years old with hepatitis C virus genotype 1 infection. Hepatology. 2016. doi:10.1002/hep.28995. The recently published phase 2, multi-center, open-label study to evaluate the efficacy and safety of ledipasvir-sofosbuvir in adolescents with chronic HCV genotype 1 infection is a breakthrough in pediatric hepatology field. This study has blazed a trail to a safe, stepwise evaluation of DAAs as all-oral DAAs regimens for the pediatric population
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Conflict of Interest
Kathleen B. Schwarz reports grants from Gilead, grants from Roche/Genentech, and personal fees from Up to Date, outside the submitted work.
Wikrom Karnsakul has had a relationship with Gilead as a sponsor for an Open-Label, Multicenter, Multi-cohort, Single-Arm Study to Investigate the Safety and Efficacy of Sofosbuvir + Ribavirin in Adolescents and Children with Genotype 2 or 3 Chronic HCV Infection and a Phase 2, Open-Label, Multicenter, Multi-cohort Study to Investigate the Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination in Adolescents and Children with Chronic HCV-Infection and a Long Term Follow-up Registry for Adolescent and Pediatric Subjects Who Received a Gilead Hepatitis C Virus Direct Acting Antiviral (DAA) in Chronic Hepatitis C Infection Trials.
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.
This article is part of the Topical Collection on Hepatitis C
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Schwarz, K.B., Karnsakul, W. Treatment of Hepatitis C in Children. Curr Hepatology Rep 16, 18–25 (2017). https://doi.org/10.1007/s11901-017-0334-1
- Hepatitis C
- Viral hepatitis
- Pediatric liver disease
- Direct acting antivirals
- Pegylated interferon and ribavirin
- Epidemiology of HCV in children