Journal of Hepatology
Volume 49, Issue 6 , Pages 884-891 , December 2008

The role of serial measurement of serum HBV DNA levels in patients with chronic HBeAg(−) hepatitis B infection: Association with liver disease progression. A prospective cohort study

  • George Zacharakis

      Affiliations

    • Unit of Preventive Medicine, Social Security Institute, Alexandroupolis, Greece
    • Second Department of Internal Medicine, Athens University, School of Medicine, Hippokration General Hospital, Athens, Greece
    • Corresponding Author InformationCorresponding author. Tel.: +30 2107774742; fax: +30 2107706871.
    • ,
  • John Koskinas

      Affiliations

    • Second Department of Internal Medicine, Athens University, School of Medicine, Hippokration General Hospital, Athens, Greece
    • ,
  • Stamatia Kotsiou

      Affiliations

    • B Academic Department of Medicine, Democritus University of Thrace Medical School, Alexandroupolis, Greece
    • ,
  • Fevronia Tzara

      Affiliations

    • Unit of Preventive Medicine, Social Security Institute, Alexandroupolis, Greece
    • ,
  • Nikolaos Vafeiadis

      Affiliations

    • Unit of Preventive Medicine, Social Security Institute, Alexandroupolis, Greece
    • ,
  • Menelaos Papoutselis

      Affiliations

    • Unit of Preventive Medicine, Social Security Institute, Alexandroupolis, Greece
    • ,
  • Eustratios Maltezos

      Affiliations

    • B Academic Department of Medicine, Democritus University of Thrace Medical School, Alexandroupolis, Greece
    • ,
  • Eleftherios Sivridis

      Affiliations

    • Department of Pathology, Democritus University of Thrace Medical School, Alexandroupolis, Greece
    • ,
  • Kostantinos Papoutselis

      Affiliations

    • Unit of Preventive Medicine, Social Security Institute, Alexandroupolis, Greece

Received 30 March 2008 ,Accepted 10 June 2008.

References 

  1. Lee WM. Hepatitis B virus infection. N Engl J Med. 1997;337:1733–1745
  2. Beasley WM. Hepatitis B virus-the major etiology of hepatocellular carcinoma. Cancer. 1988;61:1942–1956
  3. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507–539
  4. Sanchez-Tapias JM, Costa J, Mas A, Bruguera M, Rodes J. Influence of hepatitis B virus genotype on the long-term outcome of chronic hepatitis B in Western patients. Gastroenterology. 2002;123:1848–1856
  5. Hoofnagle JH, Shafritz DA, Popper H. Chronic type B hepatitis and the “healthy” HBsAg carrier state. Hepatology. 1987;7:758–763
  6. Villeneuve JP. The natural history of chronic hepatitis B virus infection. J Clin Virol. 2005;25:S139–S142
  7. McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25:3–8
  8. Lai CL, Ratziou V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. 2003;362:2089–2094
  9. Merican I, Guan A, Amarapuka D, Alexander MJ, Chupatti A, Chien RN, et al. Chronic hepatitis B virus infection in Asian countries. J Gastroenterol Hepatol. 2000;15:1356–1361
  10. Chang MH, Hsu HY, Hsu HC, NI YH, Chen JS, Chen DS. The significance of spontaneous hepatitis B e antigen seroconversion in childhood; with special emphasis on the clearance of hepatitis B e antigen before 3 years of age. Hepatology. 1955;22:1387–1392
  11. Chen CJ, YU MW, Liaw YF. Epidemiological characteristics and risk factors of hepatocellular carcinoma. J Gastroenterol Hepatol. 1997;12:S294–S308
  12. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73
  13. IIoeje UH, Yang HI, SU J, Jen CL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678–686
  14. Yuen MF, Lai CL. Treatment of chronic hepatitis B. Lancet Infect Dis. 2001;1:232–241
  15. Dienstag JL, Sciff ER, Wright TL, Perrilo RP, Hann HW, Goodman Z, et al. Lamivudine as an initial treatment for chronic hepatitis B in the United States. N Engl J Med. 1999;341:1256–1263
  16. Andreone P, Gramenzi A, Cursaro C, Bisseli M, Cammà C, Trevisani F, et al. High risk of hepatocellular carcinoma in anti-HBe positive liver cirrhosis patients developing lamivudine resistance. J Viral Hepatol. 2004;11:439–442
  17. Di Marco V, Marzano A, Lampertico P, Andreone P, Santantonio T, Almasio PL, et al. Clinical outcomes of HBeAg-negative chronic hepatitis B in relation to virological response o lamivudine. Hepatology. 2004;40:883–891
  18. Fattovich G, Giustina G, Scham SW, Hadziyannis S, Sanchez-Tapias J, Almasio P, et al. Occurrence of hepatocellular carcinoma and decompensation in western European patients with cirrhosis type B. The Eurohep study group on hepatitis B virus and cirrhosis. Hepatology. 1995;21:77–82
  19. Manno M, Cammà M, Schepis F, Bassi F, Gelmini R, Giannini F, et al. Natural history of chronic HBV carriers in Northern Italy: morbidity and mortality after 30 years. Gastroenterology. 2004;127:756–763
  20. Bellentani S, Dal Molin G, Miglioli L, Saveria Croce L, Massuti F, Castiglione A, et al. Natural history of HBV infection: a 9 years follow-up of the Dionysus cohort. J Hepatol. 2002;36:S228
  21. Dragosic B, Ferenci P, Hitachan E, Denk H. Long term follow-up study of asymptomatic HBsAg-positive voluntary blood donors in Austria. A clinical and histological evaluation of 242 cases. Hepatology. 1987;7:302–306
  22. Scheuer PJ. Classification of chronic hepatitis: a need for reassessment. J Hepatol. 1991;13:372–374
  23. Hadziyannis S, Vassilopoulos D. Hepatitis B e antigen negative chronic hepatitis B. Hepatology. 2001;34:617–624
  24. Zacharakis G, Koskinas J, Kotsiou S, Papoutselis M, Tzara F, Vafeiadis N, et al. Natural History of chronic HBV infection in children of different ethnic origins: a study with up to 12 years follow-up in northern Greece. Part of the Interreg I-II/EC-Project. J Pediatr Gastroenterol Nutr. 2007;44:84–91
  25. LoK AS, Lai CL, Wu PC, Leung EKY, Lam TS. Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection. Gastroenterology. 1987;92:1839–1843
  26. Perillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology. 2001;120:1009–1022
  27. Hsu YS, Chien RN, Yeh CT, Sheen IS, Chiou HY, Chu CM, et al. Long-term outcome following spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology. 2002;35:1522–1527
  28. Bellentani S, Dal Molin G, Miglioli L, Saveria Croce L, Massuti F, Castiglione A, et al. Natural history of HBV infection: a 9 years follow-up of the Dionysus cohort. J Hepatol. 2002;36:S228
  29. Dragosic B, Ferenci P, Hitachan E, Denk H. Long term follow-up study of asymptomatic HBsAg-positive voluntary blood donors in Austria. A clinical and histological evaluation of 242 cases. Hepatology. 1987;7:302–306
  30. de Franchis R, Meucci G, Vecchi M, Tatarella M, Colombo M, Del Ninno E, et al. The natural history of asymptomatic hepatitis B surface antigen carriers. Ann Intern Med. 1993;118:191–194
  31. ter Borg F, ten Kate J, Cuypers HT, Leentvaar-kuipers A, Osting J, Weirtheim-van Dillen PM, et al. Relation between laboratory test results and histological hepatitis activity in individuals positive for hepatitis B surface antigen and antibodies to hepatitis B e antigen. Lancet. 1998;351:1914–1918
  32. Nakamoto Y, Guidotti LG, Kuhlen CV, Fowler P, Chisari FV. Immune pathogenesis of hepatocellular carcinoma. J Exp Med. 1998;188:341–350
  33. Yuen MF, Lai CL. Towards control of hepatitis B in the Asian-Pacificregion-natural history of chronic hepatitis B virus infection. J Gastroentero Hepatol. 2000;15:E20–E24
  34. Maruyama T, lino S, Koike K, Yasuda K, Milich DR. Serology of acute exaberation in chronic hepatitis B virus infection. Gastroenterology. 1993;105:1141–1151
  35. Liaw YF, Pao CC, Chu CM, Sheen IS, Huang MJ. Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type b hepatitis. Hepatology. 1987;7:1–3
  36. Yuen MF, Yuan HJ, Wong DK, Yuen JC, Wong WM, Chan AO, et al. Prognostic determinants for chronic hepatitis B in Asians; therapeutic implications. Gut. 2005;54:1610–1614
  37. Chu CJ, Hussain M, Lok AS. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology. 2002;36:1408–1415
  38. Shao J, Wang H, Sun Y, Zhang LF, Li J, Dong JO. Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B. WJG. 2007;13:2104–2107
  39. Lindh M, Horal P, Dhillon AP, Norkrans G. Hepatitis B virus DNA levels, precore mutations, genotypes and histological activity in chronic hepatitis B. J Viral Hepat. 2000;7:258–267
  40. Mommeja-Marin H, Mondou E, Blum MR, Rousseau F. Serum HBV DNA as a marker of efficacy during therapy for chronic HBV infection: analysis and review of the literature. Hepatology. 2003;2003:1309–1319
  41. Manesis EK, Papatheodoridis GV, Sevastianos V, Cholongitas E, Papaioannou C, Hadziyannis SJ. Significance of hepatitis B viremia levels determined by a quantitative polymerase chain reaction assay in patients with hepatitis B e antigen-negative chronic hepatitis B virus infection. Am J Gastroenterol. 2003;98:2261–2267
  42. Martinot-Peignoux M, Boyer N, Colombat M, Akremi R, Pham BN, Olivier S. Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers. J Hepatol. 2002;36:543–546
  43. Bortolotti F, Guido M, Bartolacci S, Cadrobbi P, Crivellaro C, Noventa F, et al. Chronic Hepatitis B in children after e antigen seroconversion: final report of a 29-year longitudinal study. Hepatology. 2006;43:556–562

☆ Preliminary results of this study were presented at the Liver Meeting 2007 of the American Association for the Study of Liver Diseases. This study is supported by a grant from the Subprogram 5, “Quality of Life and Environment” of the European Community Project Interreg I and II .

PII: S0168-8278(08)00414-5

doi: 10.1016/j.jhep.2008.06.009

Journal of Hepatology
Volume 49, Issue 6 , Pages 884-891 , December 2008

Article Tools

* Image Usage & Resolution