Role of IgM antibody to hepatitis B core antigen in the diagnosis of hepatitis B exacerbations

  • G. Colloredo Mels
  • G. Bellati
  • G. Leandro
  • Maurizia Rossana Brunetto
  • O. Vicari
  • P. Piantino
  • M. Borzio
  • G. Angeli
  • G. Ideo
  • F. Bonino
Conference paper
Part of the Archives of Virology Supplementum book series (ARCHIVES SUPPL, volume 8)


IgM anti-HBc levels were measured by the IMx Core-M Abbott assay in 939 serum samples in order to define a specific and sensitive cut-off value for diagnosis of chronic hepatitis B. The sera used were obtained from 52 chronic HBV patients and 10 HBV carriers with HCV or HDV co-infections and 155 asymptomatic subjects without evidence of liver disease. A Youden index value of 95.4% with 98% sensitivity and 97.4% specificity was obtained for an IMx Index value of 0.204 as cut-off. A one-year follow-up study with monthly tests has shown that quantitative analysis of IgM anti-HBc can serve as a non-invasive tool for monitoring HBV infection, and provides an accurate diagnosis of hepatitis B exacerbations. Significant elevations of IgM anti-HBc levels were associated with hepatitis B excerbations in 96.2% of the cases but with none of the ALT flare-ups observed in HCV or HDV infected individuals. These results suggest that quantitative analysis of IgM anti-HBc provides the highest degree of confidence in definition of spontaneous and therapy-induced exacerbations or remissions of hepatitis B.


Chronic Hepatitis Core Antigen Chronic Type Chronic Persistent Hepatitis Chronic HBsAg Carrier 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Brunetto MR, Arrigoni A, Toti M, Almi P, Zanetti A, Ferroni P, Doris R, Aneloni V, Crovari P, Coppola RC, Bonino F (1988) The diagnostic significance of IgM antibody to B core antigen, revisited. Ital J Gastroenterol 20: 167–170Google Scholar
  2. 2.
    Brunetto MR, Torrani Cerentia M, Olivieri F, Piantino P, Randone A, Calvo PL, Bonino F (1993) Monitoring the natural course and response to therapy of chronic hepatitis B with an automated semi-quantitative assay for IgM anti-HBc. J Hepatol (in press)Google Scholar
  3. 3.
    Castillo I, Bartolomé J, Quiroga A, Porres JC, Carreno V (1990) Detection of HBeAg/antiHBe immune complexes in the reactivation of hepatitis B virus replication among antiHBe chronic carriers. Liver 10: 79–84PubMedGoogle Scholar
  4. 4.
    Colloredo Mels G, Bellati G, Leandro G, Brunetto MR, Vicari O, Borzio M, Piantino P, Fornaciari G, Scudeller G, Angeli G, Bonino F, Ideo G (1993) Fluctuations of viremia, aminotransferases and IgM antibody to hepatitis B core antigen in chronic hepatitis B patients with disease exacerbations. Liver (in press)Google Scholar
  5. 5.
    Davis GD, Hoofnagle JH, Waggoner JG (1984) Spontaneous reactivation of chronic hepatitis B virus infection. Gastroenterology 86: 230–235PubMedGoogle Scholar
  6. 6.
    Davis GL, Hoofnagle JH (1985) Reactivation of chronic type B hepatitis presenting as acute viral hepatitis. Ann Intern Med 102: 762–765PubMedGoogle Scholar
  7. 7.
    Davis GL, Hoofnagle JH (1987) Reactivation of chronic hepatitis B virus infection. Gastroenterology 92: 2028–2031PubMedGoogle Scholar
  8. 8.
    Eble K, Clemens J, Krenc C, Rynning M, Stojak J, Stuckmann J, Hutten P, Nelson L, Du Charme L, Hojvat S, Mimms L (1991) Differential diagnosis of acute viral hepatitis using rapid, fully automated immunoassays. J Med Virol 33: 139–150PubMedCrossRefGoogle Scholar
  9. 9.
    Fattovich G, Brollo L, Alberti A, Realdi G, Pontisso P, Giustina G, Roul A (1990) Spontaneous reactivation of hepatitis B virus infection in patients with chronic type B hepatitis. Liver 10: 141–146PubMedGoogle Scholar
  10. 10.
    Feinstein AR (1985) Clinical epidemiology: the architecture of clinical research. W.B. Saunders, Philadelphia, pp 434–437Google Scholar
  11. 11.
    Gayno S, Marcellin P, Loriot MA, Martinot-Peignoux M, Levy P, Erlinger S, Benhamou JP (1992) Detection of serum HBV-DNA by polymerase chain reaction ( PCR) in patients before reactivation of chronic hepatitis B. J Hepatol 14: 357–360PubMedCrossRefGoogle Scholar
  12. 12.
    Gerlich WH, Luer W, Thomssen R, The Study Group for Viral hepatitis of the Deutsche Forschungsgemeinschaft (1980) Diagnosis of acute and inapparent hepatitis B virus infection by measurement of IgM antibody to hepatitis B core antigen. J Infect Dis 142: 85–101Google Scholar
  13. 13.
    Gerlich WH, Uy A, Lambrecht F, Thomssen R (1986) Cut-off levels of IgM antibody against viral core antigen for differentiation of acute, chronic and past hepatitis B virus infections. J Clin Microbiol 24: 288–293PubMedGoogle Scholar
  14. 14.
    Gupta S, Govindarajan S, Fong T-L, Redeker A (1990) Spontaneous reactivation in chronic hepatitis B: patterns and natural history. J Clin Gastroenterol 12: 562–568PubMedCrossRefGoogle Scholar
  15. 15.
    Koike K, Iino K, Kurai K, Mitamura K, Endo Y, Oka H (1987) IgM anti-HBc in antiHBe positive chronic type B hepatitis with acute exacerbations. Hepatology 7: 573–576PubMedCrossRefGoogle Scholar
  16. 16.
    Kryger P (1985) Significance of anti-HBc IgM in the differential diagnosis of viral hepatitis. J Virol Methods 10: 283–289PubMedCrossRefGoogle Scholar
  17. 17.
    Krogsgaard K, Aldershvile J, Kryger P, Pedersen C, Anderson P, Dalboge H, Nielsen JO, Hansson BG (1990) Reactivation of viral replication in antiHBe positive chronic HBsAg carriers. Liver 10: 54–58PubMedGoogle Scholar
  18. 18.
    Kuhns MC, McNamara AL, Perillo RP, Cabal CM, Campbell CR (1989) Quantitation of hepatitis B viral DNA by solution hybridisation: comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy. J Med Virol 27: 274–281PubMedCrossRefGoogle Scholar
  19. 19.
    Lavarini C, Farci P, Chiaberge E, Veglio V, Giacobbi D, Crivelli O, Rizzetto M (1983) IgM antibody against hepatitis B core antigen (IgM anti-HBc): diagnostic and prognostic significance in acute HBsAg positive hepatitis. Br J Med 287: 1254–1256CrossRefGoogle Scholar
  20. 20.
    Levy P, Marcellin P, Martinot-Peignoux M, Degott C, Nataf J, Benhamou JP (1990) Clinical course of spontaneous reactivation of hepatitis B virus infection in patients with cronic hepatitis B. Hepatology 12: 570–574PubMedCrossRefGoogle Scholar
  21. 21.
    Liaw Y-F, Chu C-M, Su I-J, Huang M-J, Lin D-Y, Chang-Chien C-S (1983) Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis. Gastroenterology 84: 216–219PubMedGoogle Scholar
  22. 22.
    Liaw Y-F, Yang S-S, Chen T-J, Chu C-M (1985) Acute exacerbation in hepatitis B e antigen positive chronic type B hepatitis. A clinicopathological study. J Hepatol 1: 227–233PubMedCrossRefGoogle Scholar
  23. 23.
    Liaw Y-F, Tai D-I, Chu C-M, Pao CC, Chen T-J (1987) Acute exacerbation in chronic type B hepatitis: comparison between HBeAg and antibody-positive patients. Hepatology 7: 20–23PubMedCrossRefGoogle Scholar
  24. 24.
    LiawY-F, Pao C-C, Chu C-M (1988) Changes of serum HBV-DNA in relation to serum transaminase level during acute exacerbation in patients with chronic type B hepatitis. Liver 8: 231–235PubMedGoogle Scholar
  25. 25.
    Liaw Y-F, Tai D-I, Chu C-M, Chen T-J (1988) The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 8: 493–496PubMedCrossRefGoogle Scholar
  26. 26.
    Lok ASF, Lai C-L, Wu P-C, Leung EKY, Lam T-S (1987) Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection. Gastroenterology 92: 1839–1843PubMedGoogle Scholar
  27. 27.
    Lok ASF, Lai C-L (1990) Acute exacerbations in Chinese patients with chronic hepatitis B virus ( HBV) infection. J Hepatol 10: 29–34PubMedCrossRefGoogle Scholar
  28. 28.
    Perrillo RP, Campbell CR, Sanders GE, Regenstein FG, Bodicky CJ (1984) Spontaneous clearance and reactivation of hepatitis B virus infection among male homosexuals with chronic type B hepatitis. Ann Intern Med 100: 43–46PubMedGoogle Scholar
  29. 29.
    Raimondo G, Rodino G, Smedile V, Brancatelli S, Villari D, Longo G, Squadrito G (1990) Hepatitis B virus ( HBV) markers and HBV-DNA in serum and liver tissue of patients with acute exacerbation of chronic type B hepatitis. J Hepatol 10: 271–273PubMedCrossRefGoogle Scholar
  30. 30.
    Sheen I-S, Liaw Y-F, Tai D-I, Chu C-M (1985) Hepatic decompensation associated with hepatitis B e antigen clearance in chronic type B hepatitis. Gastroenterology 89: 732–735PubMedGoogle Scholar
  31. 31.
    Smith HM, Lau JYN, Davies SE, Daniels HM, Alexander GJM, Williams R (1992) Significance of serum IgM anti-HBc in chronic hepatitis B virus infection. J Med Virol 36: 16–20PubMedCrossRefGoogle Scholar
  32. 32.
    Sjogren M, Hoofnagle JH (1985) Immunoglobulin M antibody to hepatitis B core antigen in patients with chronic type B hepatitis. Gastroenterology 85: 252–258Google Scholar
  33. 33.
    Tong MJ, Sampliner RE, Govindarajan S, Co RL (1987) Spontaneous reactivation of hepatitis B in Chinese patients with HBsAg-positive chronic active hepatitis. Hepatology 7: 713–718PubMedCrossRefGoogle Scholar
  34. 34.
    Weinstein MC, Fineberg HV (1980) Clinical decision analysis. W.B. Saunders, Philadelphia, pp 601–609Google Scholar
  35. 35.
    Youden WJ (1950) Index for rating diagnostic tests. Cancer 3: 32–35PubMedCrossRefGoogle Scholar
  36. 36.
    Zoulim F, Mimms L, Floreani M, Pichoud C, Chemin I, Kay A, Vitvitski L, Trepo C (1992) New assays for quantitative determination of viral markers in management of chronic hepatitis B virus infection. J Clin Microbiol 30: 1111–1119PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • G. Colloredo Mels
    • 1
  • G. Bellati
    • 5
  • G. Leandro
    • 2
  • Maurizia Rossana Brunetto
    • 6
    • 7
  • O. Vicari
    • 4
  • P. Piantino
    • 6
    • 7
  • M. Borzio
    • 3
  • G. Angeli
    • 1
  • G. Ideo
    • 5
  • F. Bonino
    • 6
    • 7
  1. 1.Department of Internal MedicineBolognini HospitalSeriate, BergamoItaly
  2. 2.Department of Internal Medicine Saverio De Bellis HospitalIRCCSCastellana Grotte, BariItaly
  3. 3.Department of Internal MedicineFatebenefratelli HospitalMilanoItaly
  4. 4.Department of Internal Medicine of the Transfusion CenterOOMM HospitalBergamoItaly
  5. 5.Department of Internal Medicine of the Hepatology Center “Crespi”Niguarda HospitalMilanoItaly
  6. 6.Department of Internal MedicineMolinette HospitalTorinoItaly
  7. 7.Laboratory of the Department of GastroenterologyMolinette HospitalTorinoItaly

Personalised recommendations