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Hepatitis C virus infection in children

Author
Maureen M Jonas, MD
Section Editors
Morven S Edwards, MD
Elizabeth B Rand, MD
Deputy Editor
Alison G Hoppin, MD

INTRODUCTION

Children represent only a small proportion of the hepatitis C virus (HCV) infected population. Nevertheless, a substantial number of children have chronic HCV infection and are at risk for complications. According to one report [1], there are approximately 115 million infected persons in the world, 11 million of whom are younger than 15 years of age. Eighty million are viremic, of whom 5 million are younger than 15 years of age. It has been estimated that the global health care costs for HCV-infected children and their families are hundreds of millions of dollars annually [2].

The major issues related to HCV in children will be reviewed here. Perinatal transmission of HCV is discussed separately. (See "Vertical transmission of hepatitis C virus".)

EPIDEMIOLOGY

In the United States, antibodies to HCV are present in approximately 0.2 percent of children ages 6 to 12 and in 0.4 percent of those ages 12 to 19, rates that are similar to the prevalence observed in volunteer adult blood donors but that are lower than adult prevalence based upon National Health and Nutrition Examination (NHANES) survey data [3-5]. The prevalence rate in children is based upon screening tests performed on a nationally representative sample [3]. In comparison, the frequency of cases that are clinically identified is far lower (5 percent of the expected number), suggesting that screening for and case identification of pediatric HCV are grossly inadequate [6]. The proportion of children who are HCV antibody-positive who are also HCV RNA positive is not known precisely; based upon studies in adults, it is estimated to be approximately 75 to 80 percent. (See "Epidemiology and transmission of hepatitis C virus infection".)

The prevalence is much higher (50 to 95 percent) in individuals who received blood products for conditions such as thalassemia or hemophilia before 1990 (when a first-generation enzyme-linked immunosorbent assay [ELISA] test became available and routine screening of the blood supply began) to as late as 1992 (when the second-generation ELISA test was introduced) [7-9]. Seroprevalence rates of 10 to 20 percent were reported among children with a variety of other potential exposures such as malignancy, hemodialysis, extracorporeal membrane oxygenation, or surgery for congenital heart disease in the early to mid-1990s [10-15]. A 2 percent seroprevalence rate was found in an incarcerated juvenile population in Washington, DC [16]. Most of these at-risk children are now young adults, as routine testing of the blood supply in developed countries has virtually eliminated transmission via this route.

There appears to be worldwide geographic variation in the prevalence of HCV infection in children, the reasons for which are incompletely understood. Studies in the early 1990s (which reflected populations of children who could have been exposed to contaminated blood products) reported prevalence rates ranging from 0 percent in Japan and Taiwan [17,18], 0.4 percent in Italy [19], 0.6 percent in Malaysia [20], 0.9 percent in Saudi Arabia [21], 1.4 percent in Moldova [22], and up to 14.5 percent in Cameroon [23]. Prevalence rates in Egypt were low in the 1990s among children without a history of exposure to blood products [24], but series from 2007 reported infection in 2 percent [25]. No data on prevalence in childhood are available.

                        

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Literature review current through: Nov 2016. | This topic last updated: Fri Dec 02 00:00:00 GMT+00:00 2016.
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References
Top
  1. Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014; 61:S45.
  2. El-Shabrawi MH, Kamal NM. Burden of pediatric hepatitis C. World J Gastroenterol 2013; 19:7880.
  3. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999; 341:556.
  4. Jhaveri R. Diagnosis and management of hepatitis C virus-infected children. Pediatr Infect Dis J 2011; 30:983.
  5. Denniston MM, Jiles RB, Drobeniuc J, 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.
  6. Delgado-Borrego A, Smith L, Jonas MM, et al. Expected and actual case ascertainment and treatment rates for children infected with hepatitis C in Florida and the United States: epidemiologic evidence from statewide and nationwide surveys. J Pediatr 2012; 161:915.
  7. Resti M, Azzari C, Rossi ME, et al. Hepatitis C virus antibodies in a long-term follow-up of beta-thalassaemic children with acute and chronic non-A non-B hepatitis. Eur J Pediatr 1992; 151:573.
  8. Lai ME, De Virgilis S, Argiolu F, et al. Evaluation of antibodies to hepatitis C virus in a long-term prospective study of posttransfusion hepatitis among thalassemic children: comparison between first- and second-generation assay. J Pediatr Gastroenterol Nutr 1993; 16:458.
  9. Blanchette VS, Vorstman E, Shore A, et al. Hepatitis C infection in children with hemophilia A and B. Blood 1991; 78:285.
  10. Locasciulli A, Gornati G, Tagger A, et al. Hepatitis C virus infection and chronic liver disease in children with leukemia in long-term remission. Blood 1991; 78:1619.
  11. Rossetti F, Cesaro S, Pizzocchero P, et al. Chronic hepatitis B surface antigen-negative hepatitis after treatment of malignancy. J Pediatr 1992; 121:39.
  12. Jonas MM, Zilleruelo GE, LaRue SI, et al. Hepatitis C infection in a pediatric dialysis population. Pediatrics 1992; 89:707.
  13. Greco M, Cristiano K, Leozappa G, et al. Hepatitis C infection in children and adolescents on haemodialysis and after renal transplant. Pediatr Nephrol 1993; 7:424.
  14. Nelson SP, Jonas MM. Hepatitis C infection in children who received extracorporeal membrane oxygenation. J Pediatr Surg 1996; 31:644.
  15. Ni YH, Chang MH, Lue HC, et al. Posttransfusion hepatitis C virus infection in children. J Pediatr 1994; 124:709.
  16. Murray KF, Richardson LP, Morishima C, et al. Prevalence of hepatitis C virus infection and risk factors in an incarcerated juvenile population: a pilot study. Pediatrics 2003; 111:153.
  17. Tanaka E, Kiyosawa K, Sodeyama T, et al. Prevalence of antibody to hepatitis C virus in Japanese schoolchildren: comparison with adult blood donors. Am J Trop Med Hyg 1992; 46:460.
  18. Lee SD, Chan CY, Wang YJ, et al. Seroepidemiology of hepatitis C virus infection in Taiwan. Hepatology 1991; 13:830.
  19. Gessoni G, Manoni F. Prevalence of anti-hepatitis C virus antibodies among teenagers in the Venetian area: a seroepidemiological study. Eur J Med 1993; 2:79.
  20. Lee WS, Ng KP. Seroprevalence of anti-HCV in an urban child population: a preliminary study from Kuala Lumpur. Singapore Med J 2001; 42:100.
  21. al-Faleh FZ, Ayoola EA, al-Jeffry M, et al. Prevalence of antibody to hepatitis C virus among Saudi Arabian children: a community-based study. Hepatology 1991; 14:215.
  22. Drobeniuc J, Hutin YJ, Harpaz R, et al. Prevalence of hepatitis B, D and C virus infections among children and pregnant women in Moldova: additional evidence supporting the need for routine hepatitis B vaccination of infants. Epidemiol Infect 1999; 123:463.
  23. Ngatchu T, Stroffolini T, Rapicetta M, et al. Seroprevalence of anti-HCV in an urban child population: a pilot survey in a developing area, Cameroon. J Trop Med Hyg 1992; 95:57.
  24. Khalifa AS, Mitchell BS, Watts DM, et al. Prevalence of hepatitis C viral antibody in transfused and nontransfused Egyptian children. Am J Trop Med Hyg 1993; 49:316.
  25. 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; 13:1828.
  26. Benova L, Mohamoud YA, Calvert C, Abu-Raddad LJ. Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis 2014; 59:765.
  27. Bortolotti F, Iorio R, Resti M, et al. Epidemiological profile of 806 Italian children with hepatitis C virus infection over a 15-year period. J Hepatol 2007; 46:783.
  28. Minola E, Prati D, Suter F, et al. Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C. Blood 2002; 99:4588.
  29. Casiraghi MA, De Paschale M, Romanò L, 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.
  30. Matsuoka S, Tatara K, Hayabuchi Y, et al. Serologic, virologic, and histologic characteristics of chronic phase hepatitis C virus disease in children infected by transfusion. Pediatrics 1994; 94:919.
  31. Vogt M, Lang T, Frösner G, 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.
  32. 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.
  33. Mohan P, Colvin C, Glymph C, et al. Clinical spectrum and histopathologic features of chronic hepatitis C infection in children. J Pediatr 2007; 150:168.
  34. Matsuoka S, Tatara K, Hayabuchi Y, et al. Post-transfusion chronic hepatitis C in children. J Paediatr Child Health 1994; 30:544.
  35. European Paediatric Hepatitis C Virus Network. Three broad modalities in the natural history of vertically acquired hepatitis C virus infection. Clin Infect Dis 2005; 41:45.
  36. Jonas MM, Baron MJ, Bresee JS, Schneider LC. Clinical and virologic features of hepatitis C virus infection associated with intravenous immunoglobulin. Pediatrics 1996; 98:211.
  37. Jara P, Resti M, Hierro L, et al. Chronic hepatitis C virus infection in childhood: clinical patterns and evolution in 224 white children. Clin Infect Dis 2003; 36:275.
  38. Badizadegan K, Jonas MM, Ott MJ, et al. Histopathology of the liver in children with chronic hepatitis C viral infection. Hepatology 1998; 28:1416.
  39. Guido M, Rugge M, Jara P, et al. Chronic hepatitis C in children: the pathological and clinical spectrum. Gastroenterology 1998; 115:1525.
  40. Goodman ZD, Makhlouf HR, Liu L, et al. Pathology of chronic hepatitis C in children: liver biopsy findings in the Peds-C Trial. Hepatology 2008; 47:836.
  41. Mohan P, Barton BA, Narkewicz MR, et al. Evaluating progression of liver disease from repeat liver biopsies in children with chronic hepatitis C: a retrospective study. Hepatology 2013; 58:1580.
  42. Bortolotti F, Verucchi G, Cammà C, et al. Long-term course of chronic hepatitis C in children: from viral clearance to end-stage liver disease. Gastroenterology 2008; 134:1900.
  43. Birnbaum AH, Shneider BL, Moy L. Hepatitis C in children. N Engl J Med 2000; 342:290.
  44. Yeung LT, King SM, Roberts EA. Mother-to-infant transmission of hepatitis C virus. Hepatology 2001; 34:223.
  45. Giacchino R, Tasso L, Timitilli A, et al. Vertical transmission of hepatitis C virus infection: usefulness of viremia detection in HIV-seronegative hepatitis C virus-seropositive mothers. J Pediatr 1998; 132:167.
  46. Ceci O, Margiotta M, Marello F, et al. Vertical transmission of hepatitis C virus in a cohort of 2,447 HIV-seronegative pregnant women: a 24-month prospective study. J Pediatr Gastroenterol Nutr 2001; 33:570.
  47. Palomba E, Manzini P, Fiammengo P, et al. Natural history of perinatal hepatitis C virus infection. Clin Infect Dis 1996; 23:47.
  48. Bortolotti F, Resti M, Giacchino R, et al. Hepatitis C virus infection and related liver disease in children of mothers with antibodies to the virus. J Pediatr 1997; 130:990.
  49. Delgado-Borrego A, Healey D, Negre B, et al. Influence of body mass index on outcome of pediatric chronic hepatitis C virus infection. J Pediatr Gastroenterol Nutr 2010; 51:191.
  50. Indolfi G, Bartolini E, Serranti D, et al. Hepatitis C in Children Co-infected With Human Immunodeficiency Virus. J Pediatr Gastroenterol Nutr 2015; 61:393.
  51. El-Kamary SS, Serwint JR, Joffe A, et al. Prevalence of hepatitis C virus infection in urban children. J Pediatr 2003; 143:54.
  52. Mack CL, Gonzalez-Peralta RP, Gupta N, et al. NASPGHAN practice guidelines: Diagnosis and management of hepatitis C infection in infants, children, and adolescents. J Pediatr Gastroenterol Nutr 2012; 54:838.
  53. Ghany MG, Strader DB, Thomas DL, et al. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49:1335.
  54. Conte D, Fraquelli M, Prati D, et al. 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.
  55. American Academy of Pediatrics. Medical evaluation of internationally adopted children for infectious diseases. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.194.
  56. Kage M, Fujisawa T, Shiraki K, et al. Pathology of chronic hepatitis C in children. Child Liver Study Group of Japan. Hepatology 1997; 26:771.
  57. Murray KF, Finn LS, Taylor SL, et al. Liver histology and alanine aminotransferase levels in children and adults with chronic hepatitis C infection. J Pediatr Gastroenterol Nutr 2005; 41:634.
  58. González-Peralta RP, Langham MR Jr, Andres JM, et al. Hepatocellular carcinoma in 2 young adolescents with chronic hepatitis C. J Pediatr Gastroenterol Nutr 2009; 48:630.
  59. Strickland DK, Riely CA, Patrick CC, et al. Hepatitis C infection among survivors of childhood cancer. Blood 2000; 95:3065.
  60. Schwarz K, Murray KF, Rosenthal P, Bansal S et al. High rates of SVR12 in adolescents treated with the combination of ledipasvir/sofosbuvir (meeting abstract #GS17). J Hepatol 2016; 64:S184.
  61. Schwarz KB, Rosenthal P, Gonzalez-Peralta R, et al. A Phase 2, 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 (meeting abstract). Hepatology 2016; 64(S1).
  62. Vegnente A, Iorio R, Saviano A, et al. Lack of intrafamilial transmission of hepatitis C virus in family members of children with chronic hepatitis c infection. Pediatr Infect Dis J 1994; 13:886.
  63. American Academy of Pediatrics. Hepatitis C. In: Red Book: 2015 Report of the Committee on Infectious Diseases, 30th, Kimberlin DW, Brady MT, Jackson MA, Long SS. (Eds), American Academy of Pediatrics, Elk Grove Village, IL 2015. p.423.
  64. Suzuki T, Omata K, Satoh T, et al. Quantitative detection of hepatitis C virus (HCV) RNA in saliva and gingival crevicular fluid of HCV-infected patients. J Clin Microbiol 2005; 43:4413.