European Journal of Pediatrics

, Volume 171, Issue 2, pp 253–258 | Cite as

Spontaneous clearance of hepatitis C virus in vertically infected children

  • Susan Farmand
  • Stefan Wirth
  • Helga Löffler
  • Tanja Woltering
  • Sybille Kenzel
  • Elke Lainka
  • Philipp Henneke
Original Paper

Abstract

Spontaneous viral clearance of hepatitis C virus (HCV) has been reported to occur in children with vertical HCV infection. However, factors which are associated with or predispose for clearance are largely unknown. In this case series we retrospectively analyzed laboratory parameters associated with spontaneous clearance of HCV in vertically infected children. The charts of six patients with documented spontaneous viral clearance by the age of 5 years were reviewed regarding clinical course, liver function tests (LFTs) and trend of HCV gene copy numbers. Spontaneous viral elimination was observed between the 25th and 52nd months of age. All patients had elevated LFTs, which peaked before 20 months of life. Peak LFT elevation was followed by normalization of LFTs and decline in viral load. These findings suggest that, in vertically HCV-infected children, a potent inflammatory response in the liver precedes viral clearance. Therefore, temporarily elevated LFTs, followed by a decline of viral load may be indicative of a near viral clearance in early childhood. Conclusion: Further investigations regarding the development of optimal treatment algorithms should take into account factors, which are associated with possible spontaneous viral resolution, such as viral genotype, favourable host factors as well as direct and indirect parameters of antiviral immunity, and the individual course of viral replication.

Keywords

Chronic hepatitis C Children Vertical transmission Spontaneous viral clearance Favourable host factors 

Abbreviations

ALT

alanine transaminase

AST

aspartate transaminase

ChLIA

chemiluminescent immunoassay

CMIA

chemiluminescent microparticle immunoassay

ECLIA

electrochemiluminescent immunoassay

HCV

hepatitis C virus

LFTs

liver function tests

PCR

polymerase chain reaction

RNA

ribonucleic acid

Notes

Conflict of Interest

All authors declare that they have no financial conflict of interest.

References

  1. 1.
    Alberti A, Benvegnù L, Boccato S, Ferrari A, Sebastiani G (2004) Natural history of initially mild chronic hepatitis C. Dig Liver Dis 36(10):646–654PubMedCrossRefGoogle Scholar
  2. 2.
    Bortolotti F, Verucchi G, Cammà C et al (2008) Italian observatory for HCV infection and hepatitis C in children. Long-term course of chronic hepatitis C in children: from viral clearance to end-stage liver disease. Gastroenterology 134:1900–1907PubMedCrossRefGoogle Scholar
  3. 3.
    Burra P (2009) Hepatitis C. Semin Liver Dis 29(1):53–65PubMedCrossRefGoogle Scholar
  4. 4.
    Casiraghi MA, De Paschale M, Romano L et al (2004) Long-term outcome (35 years) of hepatitis C after acquisition of infection through mini transfusions of blood given at birth. Hepatology 39:90–96PubMedCrossRefGoogle Scholar
  5. 5.
    Ceci O, Margiotta M, Marello F et al (2001) 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 33(5):570–575PubMedCrossRefGoogle Scholar
  6. 6.
    Chen ST, Ni YH, Chen PJ et al (2009) Low viraemia at enrollment in children with chronic hepatitis C favours spontaneous viral clearance. J Viral Hepatitis 16(11):796–801CrossRefGoogle Scholar
  7. 7.
    Chu CJ, Lee SD (2008) Hepatitis B virus/hepatitis C virus coinfection: epidemiology, clinical features, viral interactions and treatment. J Gastroenterol Hepatol 23(4):512–520PubMedCrossRefGoogle Scholar
  8. 8.
    Della Bella S, Riva A, Tanzi E et al (2005) Hepatitis C virus-specific reactivity of CD4+-lymphocytes in children born from HCV-infected women. J Hepatol 43(3):394–402PubMedCrossRefGoogle Scholar
  9. 9.
    Diepolder HM, Zachoval R, Hoffmann RM et al (1995) Possible mechanism involving T-lymphocytes response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 346(8981):1006–1007PubMedCrossRefGoogle Scholar
  10. 10.
    Donahue JG, Muñoz A, Ness PM et al (1992) The declining risk of post-transfusion hepatitis C virus infection. N Engl J Med 327(6):369–373PubMedCrossRefGoogle Scholar
  11. 11.
    Gerlach JT, Diepolder HM, Zachoval R et al (2003) Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology 125(1):80–88PubMedCrossRefGoogle Scholar
  12. 12.
    González-Peralta RP, Kelly DA, Haber B et al (2005) Interferon alfa-2b in combination with ribavirin for the treatment of chronic hepatitis C in children: efficacy, safety, and pharmacokinetics. Hepatology 42:1010–1018PubMedCrossRefGoogle Scholar
  13. 13.
    Hui CK, Belaye T, Montegrande K, Wright TL (2003) A comparison in the progression of liver fibrosis in chronic hepatitis C between persistently normal and elevated transaminase. J Hepatol 38(4):511–517PubMedCrossRefGoogle Scholar
  14. 14.
    Kanto T, Hayashi N (2006) Immunopathogenesis of hepatitis C virus infection: multifaceted strategies subverting innate and adaptive immunity. Intern Med 45(4):183–191PubMedCrossRefGoogle Scholar
  15. 15.
    Kaplan DE, Sugimoto K, Newton K et al (2007) Discordant role of CD4 T-cell response relative to neutralizing antibody and CD8 T-cell responses in acute hepatitis C. Gastroenterology 132(2):654–666PubMedCrossRefGoogle Scholar
  16. 16.
    Mangia A, Thompson AJ, Santoro R et al (2010) An IL28B polymorphism determines treatment response of hepatitis C virus genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 139(3):821–827PubMedCrossRefGoogle Scholar
  17. 17.
    Mast EE, Hwang LY, Seto DS et al (2005) Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J Infect Dis 192(11):1880–1889PubMedCrossRefGoogle Scholar
  18. 18.
    Minola E, Prati D, Suter F et al (2002) Age at infection affects the long-term outcome of transfusion-associated chronic hepatitis C. Blood 99:4588–4591PubMedCrossRefGoogle Scholar
  19. 19.
    Missale G, Bertoni R, Lamonaca V et al (1996) Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response. J Clin Invest 98:706–714PubMedCrossRefGoogle Scholar
  20. 20.
    Mohan P, Colvin C, Glymph C et al (2007) Clinical spectrum and histopathologic features of chronic hepatitis C infection in children. J Pediatr 150(2):168–174PubMedCrossRefGoogle Scholar
  21. 21.
    Mueller S, Millonig G, Seitz HK (2009) Alcoholic liver disease and hepatitis C: a frequently underestimated combination. World J Gastroenterol 15(28):3462–3471PubMedCrossRefGoogle Scholar
  22. 22.
    Neumann-Haefelin C, Timm J, Schmidt J et al (2010) Protective effect of human leukocyte antigen B27 in hepatitis C virus infection requires the presence of a genotype-specific immunodominant CD8+ T-cell epitope. Hepatology 51(1):54–62PubMedCrossRefGoogle Scholar
  23. 23.
    Palomba E, Manzini P, Fiammengo P, Maderni P, Saracco G, Tovo PA (1996) Natural history of perinatal hepatitis C virus infection. Clin Infect Dis 23(1):47–50PubMedCrossRefGoogle Scholar
  24. 24.
    Poynard T, Bedossa P, Opolon P (1997) The Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 349(9055):825–832PubMedCrossRefGoogle Scholar
  25. 25.
    Resti M, Jara P, Hierro L et al (2003) Clinical features and progression of perinatally acquired hepatitis C virus infection. J Med Virol 70(3):373–377PubMedCrossRefGoogle Scholar
  26. 26.
    Ruiz-Extremera A, Muñoz-Gámez J, Salmerón-Ruiz MA et al (2011) Genetic variation in IL28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV infected children. Hepatology 53(6):1830–1838Google Scholar
  27. 27.
    Smit C, van den Berg C, Geskus R, Berkhout B, Coutinho R, Prins M (2008) Risk of hepatitis-related mortality increased among hepatitis C virus/HIV coinfected drug users compared with drug users infected only with hepatitis C virus: a 20 year prospective study. J Acquir Immune Defic Syndr 47:221–225PubMedCrossRefGoogle Scholar
  28. 28.
    Tajiri H, Miyoshi Y, Funada S et al (2001) Prospective study of mother-to-infant transmission of hepatitis C virus. Pediatr Infect Dis J 20(1):10–14PubMedCrossRefGoogle Scholar
  29. 29.
    Takaki A, Wiese M, Maertens G et al (2000) Cellular immune responses persist and humoral responses decrease two decades after recovery from a single source outbreak of hepatitis C. Nat Med 6:578–582PubMedCrossRefGoogle Scholar
  30. 30.
    Thomas DL, Thio CL, Martin MP et al (2009) Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461:798–801PubMedCrossRefGoogle Scholar
  31. 31.
    Tovo PA, Pembrey LJ, Newell ML (2000) Persistence rate and progression of vertically acquired hepatitis C infection. European Paediatric Hepatitis C Virus Infection Network. J Infect Dis 181(2):419–424PubMedCrossRefGoogle Scholar
  32. 32.
    Villano SA, Vlahov D, Nelson KE, Cohn S, Thomas DL (1999) Persistence of viremia and the importance of long-term follow-up after acute hepatitis C infection. Hepatology 29(3):908–914PubMedCrossRefGoogle Scholar
  33. 33.
    Vogt M, Lang T, Frösner G et al (1999) 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 341(12):866–870PubMedCrossRefGoogle Scholar
  34. 34.
    Wirth S, Pieper-Boustani H, Lang T et al (2005) PEG-interferon-alpha-2b and ribavirin treatment in children and adolescents with chronic hepatitis C. Hepatology 41:1013–1018PubMedCrossRefGoogle Scholar
  35. 35.
    Yu JW, Wang GQ, Sun LJ, Li XG, Li SC (2007) Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin. J Gastroenterol Hepatol 22(6):832–836PubMedCrossRefGoogle Scholar
  36. 36.
    Zanetti AR, Tanzi E, Paccagnini S et al (1995) Mother-to-infant transmission of hepatitis C virus. Lancet 345:289–291PubMedCrossRefGoogle Scholar
  37. 37.
    Zarski JP, Bohn B, Bastie A et al (1998) Characteristic of patients with dual infection by hepatitis B and C viruses. J Hepatol 28:27–33PubMedCrossRefGoogle Scholar
  38. 38.
    Zeuzem S (2004) Heterogeneous virologic response rates to interferon-based therapy in patients with chronic hepatitis C: who responds less well? Ann Intern Med 140(5):370–381PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Susan Farmand
    • 1
    • 2
  • Stefan Wirth
    • 3
  • Helga Löffler
    • 1
  • Tanja Woltering
    • 1
  • Sybille Kenzel
    • 1
    • 2
  • Elke Lainka
    • 4
  • Philipp Henneke
    • 1
    • 2
    • 5
  1. 1.Centre for Paediatrics and Adolescent MedicineUniversity of FreiburgFreiburgGermany
  2. 2.Centre of Chronic ImmunodeficiencyUniversity of FreiburgFreiburgGermany
  3. 3.Children’s Hospital Helios Klinikum WuppertalWitten-Herdecke UniversityWittenGermany
  4. 4.Children’s HospitalUniversity Duisburg-EssenEssenGermany
  5. 5.CCI FreiburgFreiburgGermany

Personalised recommendations