Gastroenterology
Volume 135, Issue 4 , Pages 1192-1199 , October 2008

HBsAg Seroclearance in Chronic Hepatitis B in Asian Patients: Replicative Level and Risk of Hepatocellular Carcinoma

  • Man–Fung Yuen

      Affiliations

    • Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    • Corresponding Author InformationAddress requests for reprints to: Man–Fung Yuen, Prof, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong. fax: (852) 2872 5828
    • ,
  • Danny Ka–Ho Wong

      Affiliations

    • Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    • ,
  • James Fung

      Affiliations

    • Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    • ,
  • Philip Ip

      Affiliations

    • Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    • ,
  • David But

      Affiliations

    • Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    • ,
  • Ivan Hung

      Affiliations

    • Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    • ,
  • Kevin Lau

      Affiliations

    • Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    • ,
  • John Chi–Hang Yuen

      Affiliations

    • Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong
    • ,
  • Ching–Lung Lai

      Affiliations

    • Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong

Received 15 April 2008 ,Accepted 3 July 2008.

References 

  1. Sampliner RE, Hamilton FA, Iseri OA, et al. The liver histology and frequency and clearance of the hepatitis B surface antigen (HBsAg) in chronic carriers. Am J Med Sci. 1979;277:17–22
  2. Alward WLM, McMahon BJ, Hall DB, et al. The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma. J Infect Dis. 1985;151:604–609
  3. Wu TT, Hsu HC, Chen DS, et al. Clearance of hepatitis B surface antigen (HBsAg) after surgical resection of hepatocellular carcinoma. J Hepatol. 1987;4:45–51
  4. McMahon BJ, Alberts SR, Wainwright RB, et al. Hepatitis B-related sequelae (Prospective study in 1400 hepatitis B surface antigen-positive Alaska Native carriers). Arch Intern Med. 1990;150:1051–1054
  5. Liaw YF, Sheen IS, Chen TJ, et al. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology. 1991;13:627–631
  6. Hsu HY, Chang MH, Lee CY, et al. Spontaneous loss of HBsAg in children with chronic hepatitis B virus infection. Hepatology. 1992;15:382–386
  7. Da Silva LC, De Assis Madruga CL, Carrilho FJ, et al. Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis: lack of correlation with hepatitis C and D virus infection. J Gastroenterol. 1996;31:696–701
  8. Janssen HL, van Zonneveld M, Senturk H, et al. HBV 99-01 Study Group; Rotterdam Foundation for Liver Research Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123–129
  9. Lai CL, Shouval D, Lok AS, et al. BEHoLD AI463027 Study Group Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2006;354:1011–1020
  10. Yuen MF, Seto WK, Chow DHF, et al. Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease. Antivir Ther. 2007;12:1295–1303
  11. Fattovich G, Giustina G, Sanchez-Tapias J, et al. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon α therapy and disease prognosis. European Concerted Action on Viral Hepatitis (EUROHEP). Am J Gastroenterol. 1998;93:896–900
  12. Marcellin P, Martinot-Peignoux M, Loriot MA, et al. Persistence of hepatitis B virus DNA demonstrated by polymerase chain reaction in serum and liver after loss of HBsAg induced by antiviral therapy. Ann Intern Med. 1990;112:227–228
  13. Kuhns M, McNamara A, Mason A, et al. Serum and liver hepatitis B virus DNA in chronic hepatitis B after sustained loss of surface antigen. Gastroenterology. 1992;103:1649–1656
  14. Fong TL, Di Bisceglie AM, Gerber MA, et al. Persistence of hepatitis B virus DNA in the liver after loss of HBsAg in chronic hepatitis B. Hepatology. 1993;18:1313–1318
  15. Loriot MA, Marcellin P, Walker F, et al. Persistence of hepatitis B virus DNA in serum and liver from patients with chronic hepatitis B after loss of HBsAg. J Hepatol. 1997;27:251–258
  16. Yuen MF, Wong DK, Sablon E, et al. HBsAg seroclearance in chronic hepatitis B in the Chinese: virological, histological, and clinical aspects. Hepatology. 2004;39:1694–1701
  17. Huo TI, Wu JC, Lee PC, et al. Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis. Hepatology. 1998;28:231–236
  18. Marcellin P, De Ledinghen V, Dhumeaux D, et al. Non-invasive assessment of liver fibrosis in chronic hepatitis b using fibroscan. Hepatology. 2005;42(Supp 1):715A
  19. Wong DKH, Yuen MF, Poon RTP, et al. Quantification of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma. J Hepatol. 2006;45:553–559
  20. Werle-Lapostolle B, Bowden S, Locarnini S, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology. 2004;126:1750–1758
  21. Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology. 1981;1:431–435
  22. Tsang PS, Trinh H, Garcia RT, et al. Significant prevalence of histologic disease in patients with chronic hepatitis B and mildly elevated serum alanine aminotransferase levels. Clin Gastroenterol Hepatol. 2008;6:569–574
  23. Coleman PF, Chen YC, Mushahwar IK. Immunoassay detection of hepatitis B surface antigen mutants. J Med Virol. 1999;59:19–24
  24. Bréchot C, Theirs V, Kremsdorf D, et al. Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely “occult”. Hepatology. 2001;34:194–203
  25. Carman WF, Van Deursen FJ, Mimms LT, et al. The prevalence of surface antigen variants of hepatitis B virus in Papua New Guinea, South Africa, and Sardinia. Hepatology. 1997;26:1658–1666
  26. Bahn A, Gerner P, Martiné U, et al. Detection of different viral strains of hepatitis B virus in chronically infected children after seroconversion from HBsAg to anti-HBs indicating viral persistence. J Hepatol. 1997;27:973–978
  27. Komori M, Yuki N, Nagaoka T, et al. Long-term clinical impact of occult hepatitis B virus infection in chronic hepatitis B patients. J Hepatol. 2001;35:798–804
  28. Ahn SH, Park YN, Park JY, et al. Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance. J Hepatol. 2005;42:188–194
  29. Yu MC, Yuan JM, Ross RK, et al. Presence of antibodies to the hepatitis B surface antigen is associated with an excess risk for hepatocellular carcinoma among non-Asians in Los Angeles County, California. Hepatology. 1997;25:226–228
  30. Adachi H, Kaneko S, Matsushita E, et al. Clearance of HBsAg in seven patients with chronic hepatitis B. Hepatology. 1992;16:1334–1337
  31. Shiota G, Oyama K, Udagawa A, et al. Occult hepatitis B virus infection in HBs antigen-negative hepatocellular carcinoma in a Japanese population: involvement of HBx and p53. J Med Virol. 2000;62:151–158
  32. Chen YC, Sheen IS, Chu CM, et al. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection. Gastroenterology. 2002;123:1084–1089
  33. Arase Y, Ikeda K, Suzuki F, et al. Long-term outcome after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B. Am J Med. 2006;119:E9–E16

 M.-F.Y. and D.K.-H.W. contributed equally to the study.

 Conflicts of interest: There are no conflicts of interest to disclose from any authors.

PII: S0016-5085(08)01316-4

doi: 10.1053/j.gastro.2008.07.008

Gastroenterology
Volume 135, Issue 4 , Pages 1192-1199 , October 2008

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