• 1
    Blumberg BS, Alter HJ, Visnich S. A ‘New’ antigen in leukemia sera. JAMA 1965; 191: 5416.
  • 2
    Rotman Y, Brown AT, Hoofnagle JH. Evaluation of the patient with hepatitis B. Hepatology 2009; 49: S227.
  • 3
    Moucari R, Lada O, Marcellin P. Chronic hepatitis B: back to the future with HBsAg. Expert Rev Anti Infect Ther 2009; 7: 6336.
  • 4
    Chu CM, Liaw YF. Hepatitis B surface antigen seroclearance during chronic hepatitis B. Antivir Ther 2010; 15: 13343.
  • 5
    Ganem D, Prince AM. Hepatitis B virus infection – natural history and clinical consequences. N Engl J Med 2004; 350: 11829.
  • 6
    Liang TJ. Hepatitis B: the virus and disease. Hepatology 2009; 49: S1321.
  • 7
    Stibbe W, Gerlich WH. Variable protein composition of hepatitis B surface antigen from different donors. Virology 1982; 123: 43642.
  • 8
    Vanlandschoot P, Leroux-Roels G. Viral apoptotic mimicry: an immune evasion strategy developed by the hepatitis B virus? Trends Immunol 2003; 24: 1447.
  • 9
    Madalinski K, Burczynska B, Heermann KH, et al. Analysis of viral proteins in circulating immune complexes from chronic carriers of hepatitis B virus. Clin Exp Immunol 1991; 84: 493500.
  • 10
    Simon K, Lingappa VR, Ganem D. Secreted hepatitis B surface antigen polypeptides are derived from transmembrane precursor. J Cell Biol 1988; 107: 21638.
  • 11
    De Medina T, Kaktor O, Shaul Y. The S promoter of HBV is regulated by positive and negative elements. Mol Cell Biol 1988|; 46: 244955.
  • 12
    Stibbe W, Gerlich WH. Structural relationship between minor and major proteins of hepatitis B surface antigen. J Virol 1983; 46: 6268.
  • 13
    Heermann KH, Goldmann U, Schwartz W, et al. Large surface proteins of HBV containing the pre-s sequence. J Virol 1984; 45: 369402.
  • 14
    Dienes HP, Gerlich WH, Worsdorfer M, et al. Hepatic expression patterns of the large and middle hepatitis B surface proteins in viremic and non viremic chronic hepatitis B. Gastroenterology 1990; 98: 101723.
  • 15
    Lau JYN, Bain VG, Davies SE, et al. Export of intracellular HBsAg in chronic hepatitis B virus infection is related to viral replication. Hepatology 1991; 14: 41621.
  • 16
    Seeger C, Mason WS. Hepatitis B virus biology. Microbiol Mol Biol Rev 2000; 64: 5168.
  • 17
    Kimbi GC, Kramvis A, Kew MC. Integration of hepatitis B virus DNA into chromosomal DNA during acute hepatitis B. World J Gastroenterol 2005; 11: 641621.
  • 18
    Bill CA, Summers J. Genomic DNA double-strand breaks are targets for hepadnaviral DNA integration. Proc Natl Acad Sci USA 2004; 101: 1113540.
  • 19
    Nagaya T, Nakamura T, Tokino T, et al. The mode of hepatitis B virus DNA integration in chromosomes of human hepatocellular carcinoma. Genes Dev 1987; 1: 77382.
  • 20
    Thomas HC, Lemon S, Zuckerman AJ. Viral Hepatitis, 3rd ed. Massachusetts, USA: Blackwell Publishing, 2005.
  • 21
    Marcellin P, Asselah T, Boyer N. Treatment of chronic hepatitis B. J Viral Hepat 2005; 12: 33345.
  • 22
    Lee WM. Hepatitis B virus infection. N Engl J Med 1997; 337: 173345.
  • 23
    Marcellin P, Pequignot F, Delarocque-Astagneau E, et al. Mortality related to chronic hepatitis B and chronic hepatitis C in France: evidence for the role of HIV coinfection and alcohol consumption. J Hepatol 2008; 48: 2007.
  • 24
    Chu CM, Liaw YF. Hepatitis B virus-related cirrhosis: natural history and treatment. Semin Liver Dis 2006; 26: 14252.
  • 25
    Liaw YF, Chu CM. Hepatitis B virus infection. Lancet 2009; 373: 58292.
  • 26
    Hsu YS, Chien RN, Yeh CT, et al. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology 2002; 35: 15227.
  • 27
    Chu CM, Hung SJ, Lin J, Tai DI, Liaw YF. Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels. Am J Med 2004; 116: 82934.
  • 28
    Liaw YF, Sheen IS, Chen TJ, Chu CM, Pao CC. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology 1991; 13: 62731.
  • 29
    Chu CM, Liaw YF. HBsAg seroclearance in asymptomatic carriers of high endemic areas: appreciably high rates during a long-term follow-up. Hepatology 2007; 45: 118792.
  • 30
    Fattovich G, Olivari N, Pasino M, et al. Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years. Gut 2008; 57: 8490.
  • 31
    Manno M, Cammá C, Schepis F, et al. Natural history of chronic HBV carriers in northern Italy: morbidity and mortality after 30 years. Gastroenterology 2004; 127: 75663.
  • 32
    van Zonneveld M, Honkoop P, Hansen BE, et al. Long-term follow-up of alpha-interferon treatment of patients with chronic hepatitis B. Hepatology 2004; 39: 80410.
  • 33
    Moucari R, Korevaar A, Lada O, et al. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study. J Hepatol 2009; 50: 108492.
  • 34
    Lok AS, Chung HT, Liu VW, Ma OC. Long-term follow-up of chronic hepatitis B patients treated with interferon alfa. Gastroenterology 1993; 105: 18338.
  • 35
    Yuen MF, Hui CK, Cheng CC, et al. Long-term follow-up of interferon alfa treatment in Chinese patients with chronic hepatitis B infection: the effect on hepatitis B e antigen seroconversion and the development of cirrhosis-related complications. Hepatology 2001; 34: 13945.
  • 36
    Yuen MF, Wong DK, Fung J, et al. HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology 2008; 135: 11929.
  • 37
    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: 71.e916.
  • 38
    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: 2518.
  • 39
    Simonetti J, Bulkow L, McMahon BJ, et al. Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus. Hepatology 2010; 51: 15317.
  • 40
    Chen YC, Sheen IS, Chu CM, Liaw YF. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection. Gastroenterology 2002; 123: 10849.
  • 41
    Lau GKK. Hepatitis B reactivation after chemotherapy: two decades of clinical research. Hepatol Int 2008; 2: 15262.
  • 42
    European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis. B. J Hepatol 2009; 50: 22742.
  • 43
    Whitehead TP, Thorpe GHG, Carter TJN, Groucutt C, Kricka LJ. Enhanced luminescence procedure for sensitive determination of peroxidase-labelled conjugates in immunoassay. Nature 1983; 305: 1589.
  • 44
    Janssen HL, Kerhof-Los CJ, Heijtink RA, Schalm SW. Measurement of HBsAg to monitor hepatitis B viral replication in patients on alpha-interferon therapy. Antiviral Res 1994; 23: 2517.
  • 45
    Deguchi M, Yamashita N, Kagita M, et al. Quantitation of hepatitis B surface antigen by an automated chemiluminescent microparticle immunoassay. J Virol Methods 2004; 115: 21722.
  • 46
    Galli C, Orlandini E, Penzo L, et al. What is the role of serology for the study of chronic hepatitis B virus infection in the age of molecular biology? J Med Virol 2008; 80: 9749.
  • 47
    Brunetto MR, Moriconi F, Bonino F, et al. Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Hepatology 2009; 49: 114150.
  • 48
    Moucari R, Mackiewicz V, Lada O, et al. Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology 2009; 49: 11517.
  • 49
    Rijckborst V, Hansen BE, Cakaloglu Y, et al. Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology 2010; 52: 45461.
  • 50
    Moucari R, Boyer N, Ripault MP, et al. Sequential therapy with adefovir dipivoxil and pegylated interferon alfa-2a for HBeAg-negative patients. J Viral Hepat 2010. DOI: DOI: 10.1111/j.1365-2893.2010.01332.x.
  • 51
    Lau GK, Marcellin P, Brunetto M, et al. On-treatment HBsAg decline during peginterferon alfa-2a (40 kD)±lamivudine in patients with HBeAg-positive CHB as a potential predictor of durable off-treatment response. Hepatology 2008; 48: 714A.
  • 52
    Sonneveld MJ, Rijckborst V, Boucher CA, et al. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline. Hepatology 2010; 52: 12517.
  • 53
    Moucari R. Peginterferon for chronic hepatitis B: predicting success with on-treatment benchmarks. J Gastroenterol Hepatol 2010; 25: 14745.
  • 54
    Wursthorn K, Jung M, Manns MP, t al. Kinetics of HBsAg decline in HBeAg+chronic hepatitis B patients with 3 years of telbivudine treatment during the Globe study. J Hepatol 2009; 50: S9.
  • 55
    Nguyen T, Thompson AJ, Bowden S, et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B: a perspective on Asia. J Hepatol 2010; 52: 50813.
  • 56
    Jaroszewicz J, Calle Serrano B, Wursthorn K, et al. Hepatitis B surface antigen (HBsAg) levels in the natural history of hepatitis B virus (HBV)-infection: a European perspective. J Hepatol 2010; 52: 51422.
  • 57
    Brunetto MR, Oliveri F, Colombatto P, et al. Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. Gastroenterology 2010; 139: 48390.
  • 58
    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: 17508.
  • 59
    Wursthorn K, Lutgehetmann M, Dandri M, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology 2006; 44: 67584.
  • 60
    Volz T, Lutgehetmann M, Wachtler P, et al. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. Gastroenterology 2007; 133: 84352.
  • 61
    Lu L, Ye D, Wang Y, et al. Correlation between HBV cccDNA and HBsAg levels and their reduction by peginterferon alfa-2a based therapy in patients with chronic hepatitis B. Hepatology 2008; 48 (Suppl. 1): 746A.
  • 62
    Manesis EK, Papatheodoridis GV, Hadziyannis E, et al. HBsAg serum levels correlate with total liver HBV DNA but not with cccDNA. Hepatology 2008; 48 (Suppl. 1): 371A.
  • 63
    Chan HL, Wong VW, Wong GL, et al. A longitudinal study on the natural history of serum hepatitis B surface antigen changes in chronic hepatitis B. Hepatology 2010; 52: 123241.
  • 64
    Laras A, Koskinas J, Dimou E, et al. Intrahepatic levels and replicative activity of covalently closed circular hepatitis B virus DNA in chronically infected patients. Hepatology 2006; 44: 694702.
  • 65
    Thompson AJ, Nguyen T, Iser D, et al. Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology 2010; 51: 193344.
  • 66
    Biermer M, Puro R, Schneider RJ. Tumor necrosis factor alpha inhibition of hepatitis B virus replication involves disruption of capsid integrity through activation of NF-kappaB. J Virol 2003; 77: 403342.
  • 67
    Moucari R, Martinot-Peignoux M, Mackiewicz V, et al. Influence of genotype on hepatitis B surface antigen kinetics in hepatitis B e antigen-negative patients treated with pegylated interferon-alpha2a. Antivir Ther 2009; 14: 11838.
  • 68
    Bréchot C. Pathogenesis of hepatitis B virus-related hepatocellular carcinoma: old and new paradigms. Gastroenterology 2004; 127 (Suppl. 1): S5661.