Use of polymerase chain reaction and antibody tests in the diagnosis of vertically transmitted hepatitis C virus infection

  • S. L. Thomas
  • M. L. Newell
  • C. S. Peckham
  • A. E. Ades
  • A. J. Hall
Article

Abstract

Data on patterns of polymerase chain reaction (PCR) and antibody test results in infants born to hepatitis C virus (HCV)-infected mothers were systematically reviewed to aid development of optimum testing schedules and diagnostic criteria for vertically exposed infants and to facilitate early identification of infected infants. Survival and cross-sectional analyses were used to estimate the timing of initial PCR positivity and subsequent PCR negativity in infected infants, and maternal antibody loss in uninfected infants was estimated as a weighted average of individual study findings. Of 74 eligible infants with strong evidence of HCV infection, an estimated 89% (90% confidence interval, 80–95%) were first PCR positive by 3 months of age, and less than 10% had subsequent PCR negativity attributable to intermittent viraemia or resolved infection in the first 18 months of life. The negative predictive value of PCR at 3 months of age was greater than 98% at an assumed rate of 5% vertical transmission, but as low as 88% at 25% transmission. The inclusion of 22 infants, each with a single PCR-positive result, increased the estimated frequency of resolved infections but made little difference to other estimates. A minority of PCR-positive infants had periods of antibody negativity by second- or third-generation assays, and among 297 uninfected infants, maternal antibody was not detected beyond 18 months. Thus, the majority of infected infants may be persistently PCR positive from 3 months of age, and the negative predictive value of PCR at 3 months is generally high. However, poor repeatability of PCR, inadequate infant follow-up, and inclusion of postnatally infected infants limits interpretation of the pooled data. Further studies using standardised PCR methodologies are needed.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Roudot-Thoraval F, Pawlotsky J, Thiers V, Deforges L, Girollet P, Guillot F, Huraux C, Aumont B, Brechot C, Dhumeaux D: Lack of mother-to-infant transmission of hepatitis C virus in human immunodeficiency virus-seronegative women: a prospective study with hepatitis C virus RNA testing. Hepatology 1993, 17: 772–777.Google Scholar
  2. 2.
    Zanetti AR, Tanzi E, Paccagnini S, Principi N, Pizzocolo G, Caccamo ML, D'Amico E, Cambiè G, Vecchi L, and the Lombardy Study Group on Vertical HCV Transmission: Mother-to-infant transmission of hepatitis C virus. Lancet 1995, 345:289–291.Google Scholar
  3. 3.
    Ohto H, Terazawa S, Sasaki N, Sasaki N, Hino K, Ishiwata C, Kako M, Ujiie N, Endo C, Matsui A, Okamato H, Mishiro S, and the Vertical Transmission of Hepatitis C Virus Collaborative Study Group: Transmission of hepatitis C virus from mothers to infants. New England Journal of Medicine 1994, 330: 744–750.Google Scholar
  4. 4.
    Thaler MM, Park C, Landers DV, Wara DW, Houghton M, Veereman-Wauters G, Sweet RL, Han JH: Vertical transmission of hepatitis C virus. Lancet 1991, 338: 17–18.Google Scholar
  5. 5.
    Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ: A review of hepatitis C virus vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or HIV infection. International Journal of Epidemiology 1997, (in press).Google Scholar
  6. 6.
    Watanabe J, Matsumoto C, Fujimura K, Shimada T, Yoshizawa H, Okamoto H, Iizuka H, Tango T, Ikeda H, Endo N, Mazda T, Nojiri T, Aoyama K, Kanemitsu K, Yamano H, Mizui M, Yokoishi F, Tokunaga K, Nishioka K: Predictive value of screening test for persistent hepatitis C virus infection evidenced by viraemia — Japanese experience. Vox Sanguinis 1993, 65: 199–203.Google Scholar
  7. 7.
    Turnbull BW: The empirical distribution function with arbitrarily grouped, censored and truncated data. Journal of the American Statistical Association 1976, 38: 290–295.Google Scholar
  8. 8.
    Sprott DA, Kalbfleisch JD: Examples of likelihoods and comparison with point estimates and large sample approximations. Journal of the American Statistical Association 1969, 64:468–484.Google Scholar
  9. 9.
    Meng Z, Sun Y, Sun D, Liu C, Copland J, Gowans EJ: A dynamic study of viraemia in chronic hepatitis C infection. Journal of Gastroenterology and Hepatology 1994, 9: 242–244.Google Scholar
  10. 10.
    Alter MJ, Margolis HS, Krawczynski K, Judson FN, Mares A, Alexander WJ, Hu PY, Miller JK, Gerber MA, Sampliner RE, Meeks EL, Beach MJ: The natural history of community-acquired hepatitis C in the United States. New England Journal of Medicine 1992, 327: 1899–1905.Google Scholar
  11. 11.
    Hennekens CH, Buring JE: Epidemiology in medicine. Little, Brown, Boston, 1987, p. 337.Google Scholar
  12. 12.
    Paccagnini S, Principi N, Massironi E, Tanzi E, Romano L, Muggliasca ML, Ragni MC, Salvaggio L: Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population. Pediatric Infectious Disease Journal 1995, 14: 195–199.Google Scholar
  13. 13.
    Maccabruni A, Caselli D, Mondelli M, Degioanni M, Cerino A: Vertical transmission of hepatitis C virus and HIV. AIDS 1993, 7: 1024–1025.Google Scholar
  14. 14.
    Maccabruni A, Bossi G, Caselli D, Cividini A, Silini E, Mondelli MU: High efficiency of vertical transmission hepatitis C virus among babies born to human immunodeficiency virus-negative women. Pediatric Infectious Disease Journal 1995, 14: 921–922.Google Scholar
  15. 15.
    Resti M, Azzari C, Lega L, Rossi ME, Zammarchi E, Novembre E, Vierucci A: Mother-to-infant transmission of hepatitis C virus. Acta Paediatrica 1995, 84: 251–255.Google Scholar
  16. 16.
    Ercilla MG, Fortuny C, Roca A, Celis R, Coll O, Torne A, Gil C, Bruguera M, Barrera JM, Jimenez R, Rodes J: Mother-to-infant transmission of hepatitis C virus — a prospective study. In: Mishiro S, Nishioka K, Oda T, Suzuki H (ed): Viral hepatitis and liver disease: proceedings of the International Symposium on Viral Hepatitis and Liver Disease, Tokyo, Japan. Williams & Wilkins, Baltimore, 1994, p. 474–477.Google Scholar
  17. 17.
    Zuccotti GV, Ribero ML, Giovannini M, Fasola M, Riva E, Portera G, Biasucci G, Decarlis S, Profeta ML, Tagger A: Effect of hepatitis C genotype on mother-to-infant transmission of virus. Journal of Pediatrics 1995, 127: 278–280.Google Scholar
  18. 18.
    Giacchino R, Picciotto A, Tasso L, Timitilli A, Sinelli N: Vertical transmission of hepatitis C. Lancet 1995, 345: 1123.Google Scholar
  19. 19.
    Wejstal R, Widell A, Mansson A, Hermodsson S, Norkrans G: Mother-to-infant transmission of hepatitis C virus. Annals of Internal Medicine 1992, 117: 887–890.Google Scholar
  20. 20.
    Lam JPH, McOmish F, Burns SM, Yap PL, Mok JYQ, Simmonds P: Infrequent vertical transmission of hepatitis C virus. Journal of Infectious Diseases 1993, 167: 572–576.Google Scholar
  21. 21.
    Kojima T, Yamanaka T: Transmission routes of hepatitis C virus: analysis of anti-HCV-positive pregnant women and their family members. Acta Obstetrica et Gynaecologica Japonica 1994, 46: 573–580.Google Scholar
  22. 22.
    Maggiore G, Ventura A, De Giacomo C, Silini E, Cerino A, Mondelli MU: Vertical transmission of hepatitis C. Lancet 1995, 345: 1122.Google Scholar
  23. 23.
    Lambruschini N, Costa J, Sanchez-Tapias JM, Olmedo E, Lopez-Labrador X, Vilardell J, Rodes J, Jimenez-de-Anta MT: Perinatal transmission of hepatitis C virus from a mother without detectable antibodies to the virus. Clinical Infectious Diseases 1994, 18: 1027.Google Scholar
  24. 24.
    Manzini P, Saracco G, Cerchier A, Riva C, Musso A, Ricotti E, Palomba E, Scolfaro C, Verme G, Bonino F, Tovo PA: Human immunodeficiency virus infection as risk factor for mother-to-child hepatitis C virus transmission; persistence of anti-hepatitis C virus in children is associated with the mother's anti-hepatitis C virus immunoblotting pattern. Hepatology 1995, 21: 328–332.Google Scholar
  25. 25.
    Nagata I, Iizuka T, Harada Y, Okada T, Matsuda R, Tanaka Y, Tanimoto K, Shiraki K: Prospective study of mother-to-infant transmission of hepatitis C virus. In: Mishiro S, Nishioka K, Oda T, Suzuki H (ed): Viral hepatitis and liver disease: proceedings of the International Symposium on Viral Hepatitis and Liver Disease, Tokyo, Japan. Williams & Wilkins, Baltimore, 1994, p. 468–470.Google Scholar
  26. 26.
    Matsubara T, Sumazaki R, Takita H: Mother-to-infant transmission of hepatitis C virus: a prospective study. European Journal of Pediatrics 1995, 154: 973–978.Google Scholar
  27. 27.
    Palomba E, Manzini P, Fiammengo P, Maderni P, Saracco G, Tovo P: Natural history of perinatal hepatitis C virus infection. Clinical Infectious Diseases 1996, 23: 47–50.Google Scholar
  28. 28.
    Takase S, Sato I, Sawada M, Takada A: Studies on intra-familial transmission of hepatitis C virus: an evidence for transplacental vertical transmission from mother to baby. International Hepatology Communications 1993, 1: 204–208.Google Scholar
  29. 29.
    Uehara S, Abe Y, Saito T, Yoshida Y, Wagatsuma S, Okamura K, Yajima A, Mandai M: The incidence of vertical transmission of hepatitis C virus. Tohoku Journal of Experimental Medicine 1993, 171: 195–202.Google Scholar
  30. 30.
    Novati R, Thiers V, D'Arminio Monforte A, Maisonneuve P, Principi N, Conti M, Lazzarin A, Brechot C: Mother-to-child transmission of hepatitis C virus detected by nested polymerase chain reaction. Journal of Infectious Diseases 1992, 165:720–723.Google Scholar
  31. 31.
    Koseki S: Mother-to-infant transmission of hepatitis C virus. Acta Obstetrica et Gynaecologica Japonica 1994, 46: 1322–1328.Google Scholar
  32. 32.
    Moriya T, Sasaki F, Mizui M, Ohno N, Mohri H, Mishiro S, Yoshizawa H: Transmission of hepatitis C virus from mothers to infants: its frequency and risk factors revisited. Biomedicine and Pharmacotherapy 1995, 49: 59–64.Google Scholar
  33. 33.
    Degos F, Maisonneuve P, Thiers V, Noel L, Erlinger S, Brechot C, Benhamou JP: Neonatal transmission of HCV from mother with chronic hepatitis. Lancet 1991, 338: 758.Google Scholar
  34. 34.
    Weiner AJ, Thaler MM, Crawford K, Kansopon J, Ching K, Hall JE, Hu F, Chien D, Houghton M: HCV-positive, HIV-1-negative mothers transmit HCV. In: Mishiro S, Nishioka K, Oda T, Suzuki H (ed): Viral hepatitis and liver disease: proceedings of the International Symposium on Viral Hepatitis and Liver Disease, Tokyo, Japan. Williams & Wilkins, Baltimore, 1994, p. 463–467.Google Scholar
  35. 35.
    Kong M, Chung J: Fatal hepatitis C in an infant born to a hepatitis C positive mother. Journal of Pediatric Gastroenterology and Nutrition 1994, 19: 460–463.Google Scholar
  36. 36.
    Giorlandino C, Gambuzza G, D'alessio P, Morgani AR: Neonatal blood tests to exclude caesarean section as a cause of maternal-fetal transmission of hepatitis C. Lancet 1995, 346: 908.Google Scholar
  37. 37.
    Chang M, Ni Y, Hwang L, Lin K, Lin H, Chen P, Lee C, Chen D: Long term clinical and virologic outcome of primary hepatitis C virus infection in children: a prospective study. Pediatric Infectious Disease Journal 1994, 13: 769–773.Google Scholar
  38. 38.
    Fischler B, Lindh G, Lindgren S, Forsgren M, Von Sydow M, Sangfelt P, Alaeus A, Harland L., Enockson E, Nemeth A: Vertical transmission of hepatitis C virus infection. Scandinavian Journal of Infectious Diseases 1996, 28:353–356.Google Scholar
  39. 39.
    Grayson ML, Braniff KM, Bowden DS, Turnidge JD: Breastfeeding and the risk of vertical transmission of hepatitis C virus. Medical Journal of Australia 1996, 163:107.Google Scholar
  40. 40.
    Kudesia G, Ball G, Irving WL: Vertical transmission of hepatitis C. Lancet 1995, 345: 1122.Google Scholar
  41. 41.
    Polywka S, Feucht H, Zîllner B, Laufs R: Hepatitis C virus infection in pregnancy and the risk of mother-to-child transmission. European Journal of Clinical Microbiology & Infectious Diseases 1997, 16: 121–124.Google Scholar
  42. 42.
    Zaaijer HL, Cuypers HT, Reesink HW, Winkel IN, Gerken G, Lelie PN: Reliability of polymerase chain reaction for detection of hepatitis C virus. Lancet 1993, 341: 722–724.Google Scholar
  43. 43.
    Damen M, Cuypers HTM, Zaaijer HL, Reesink HW, Schaasberg WP, Gerlich WH, Niesters HGM, Lelie PN: International collaborative study on the second Eurohep HCV-RNA reference panel. Journal of Virological Methods 1996, 58: 175–185.Google Scholar
  44. 44.
    Dhaliwal SK, Prescott LE, Dow BC, Davidson F, Brown H, Yap PL, Follett EA, Simmonds P: Influence of viraemia and genotype upon serological reactivity in screening assays for antibody to hepatitis C virus. Journal of Medical Virology 1996, 48: 184–190.Google Scholar
  45. 45.
    Kuroki T, Nishiguchi S, Fukuda K, Shiomi S, Monna T, Murata R, Isshiki G, Hayashi N, Shikata T, Kobayashi K: Mother-to-child transmission of hepatitis C virus. Journal of Infectious Diseases 1991, 164: 427–428.Google Scholar
  46. 46.
    Locasciulli A, Cavalletto D, Pontisso P, Cavalletto L, Scovena E, Uderzo C, Masera G, Alberti A: Hepatitis C virus serum markers and liver disease in children with leukemia during and after chemotherapy. Blood 1993, 82: 2564–2567.Google Scholar
  47. 47.
    Pastore M, Willems M, Cornu C, Buts JP, Reding R, de Ville de Goyet J, Rahier J, Otte JB, Yap SH, Sokal EM: Role of hepatitis C virus in chronic liver disease occurring after orthotopic liver transplantation. Archives of Disease in Childhood 1995, 72: 403–407.Google Scholar
  48. 48.
    Zaaijer HL, Mimms LT, Cuypers HT, Reesink HW, Van der Poel CL, Tasker S, Lelie PN: Variability of IgM response in hepatitis C virus infection. Journal of Medical Virology 1993, 40: 184–187.Google Scholar
  49. 49.
    Chen M, Sonnerborg A, Sallberg M: Levels of hepatitis C virus (HCV) RNA in serum and their relationship to levels of immunoglobulin M and G antibodies against HCV core protein. Journal of Clinical Microbiology 1995, 33: 778–780.Google Scholar

Copyright information

© MMV Medizin Verlag GmbH 1997

Authors and Affiliations

  • S. L. Thomas
    • 1
    • 2
  • M. L. Newell
    • 2
  • C. S. Peckham
    • 2
  • A. E. Ades
    • 2
  • A. J. Hall
    • 1
  1. 1.Infectious Disease Epidemiology UnitLondon School of Hygiene & Tropical MedicineLondonUK
  2. 2.Department of Epidemiology & BiostatisticsInstitute of Child HealthLondonUK

Personalised recommendations