Skip to main content
Hepatology International logoLink to Hepatology International
. 2009 Sep 18;3(Suppl 1):5–15. doi: 10.1007/s12072-009-9149-7

The role of quantitative hepatitis B serology in the natural history and management of chronic hepatitis B

Tin Nguyen 1, Paul Desmond 2, Stephen Locarnini 3,
PMCID: PMC2758940  PMID: 19763714

Abstract

Chronic hepatitis B (CHB) remains a serious clinical problem worldwide. Advances in molecular technology have enabled the development of sensitive assays for the detection and quantification of hepatitis B virus (HBV) nucleic acid and demonstrated a positive correlation between serum HBV DNA levels and disease progression. Assessment of specific serologic and virologic factors also plays a pivotal role in the diagnosis and effective management of individuals with CHB. Recent development of quantitative assays for intrahepatic HBV replicative intermediates, as well as hepatitis B e antigen and hepatitis B surface antigen, has spurred investigation into the relationship between these factors and response to antiviral therapy and disease progression. Recent findings from preclinical and clinical investigations indicate that these factors may have promise in identifying patients likely to respond to treatment. Additional work is needed to standardize and validate these assays before they can be considered to be of true diagnostic value. Further evaluation is needed to decide which will have the greatest clinical applicability.

Keywords: Hepatitis B virus, Assay, Intrahepatic HBV, Hepatitis B e antigen (HBeAg), Hepatitis B surface antigen (HBsAg)

Acknowledgments

The University of Wisconsin School of Medicine and Public Health and MDG Development Group gratefully acknowledge the independent educational grant from Bristol-Myers Squibb Company.

This manuscript has been supported by an independent educational grant from Bristol-Myers Squibb Company through the ACT-HBV Initiative. Editorial support in the development of this manuscript was provided by Kathleen Covino, PhD.

References

  • 1.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. doi: 10.1001/jama.295.1.65. [DOI] [PubMed] [Google Scholar]
  • 2.European Association for the Study of the Liver EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol. 2009;50:227–242. doi: 10.1016/j.jhep.2008.10.001. [DOI] [PubMed] [Google Scholar]
  • 3.Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, Tobias H. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6:1315–1341. doi: 10.1016/j.cgh.2008.08.021. [DOI] [PubMed] [Google Scholar]
  • 4.Liaw YF, Leung N, Kao JH, Piratvisuth T, Gane E, Han KH, et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2:263–283. doi: 10.1007/s12072-008-9080-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507–539. doi: 10.1002/hep.21513. [DOI] [PubMed] [Google Scholar]
  • 6.Chang TT, Gish RG, Man R, Gadano A, Sollano J, Chao YC, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354:1001–1010. doi: 10.1056/NEJMoa051285. [DOI] [PubMed] [Google Scholar]
  • 7.Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2006;354:1011–1020. doi: 10.1056/NEJMoa051287. [DOI] [PubMed] [Google Scholar]
  • 8.Lai CL, Gane E, Liaw YF, Hsu CW, Thongsawat S, Wang Y, et al. Telbivudine versus lamivudine in patients with chronic hepatitis B. N Engl J Med. 2007;357:2576–2588. doi: 10.1056/NEJMoa066422. [DOI] [PubMed] [Google Scholar]
  • 9.Marcellin P, Heathcote EJ, Buti M, Gane E, Man RA, Krastev Z, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med. 2008;359:2442–2455. doi: 10.1056/NEJMoa0802878. [DOI] [PubMed] [Google Scholar]
  • 10.Sherman M, Yurdaydin C, Sollano J, Silva M, Liaw YF, Cianciara J, et al. Entecavir for treatment of lamivudine-refractory, HBeAg-positive chronic hepatitis B. Gastroenterology. 2006;130:2039–2049. doi: 10.1053/j.gastro.2006.04.007. [DOI] [PubMed] [Google Scholar]
  • 11.Bernard F, Raymond G, Willems B, Villeneuve JP. Quantitative assessment of serum hepatitis B e antigen, IgM hepatitis B core antibody and HBV DNA in monitoring the response to treatment in patients with chronic hepatitis B. J Viral Hepat. 1997;4:265–272. doi: 10.1046/j.1365-2893.1997.00055.x. [DOI] [PubMed] [Google Scholar]
  • 12.Heijtink RA, Kruining J, Honkoop P, Kuhns MC, Hop WC, Osterhaus AD, Schalm SW. Serum HBeAg quantitation during antiviral therapy for chronic hepatitis B. J Med Virol. 1997;53:282–287. doi: 10.1002/(SICI)1096-9071(199711)53:3<282::AID-JMV18>3.0.CO;2-J. [DOI] [PubMed] [Google Scholar]
  • 13.Rodella A, Galli C, Terlenghi L, Perandin F, Bonfanti C, Manca N. Quantitative analysis of HBsAg, IgM anti-HBc and anti-HBc avidity in acute and chronic hepatitis B. J Clin Virol. 2006;37:206–212. doi: 10.1016/j.jcv.2006.06.011. [DOI] [PubMed] [Google Scholar]
  • 14.Sung JJ, Wong ML, Bowden S, Liew CT, Hui AY, Wong VW, et al. Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy. Gastroenterology. 2005;128:1890–1897. doi: 10.1053/j.gastro.2005.03.009. [DOI] [PubMed] [Google Scholar]
  • 15.Wursthorn K, Lutgehetmann M, Dandri M, Volz T, Buggisch P, Zollner B, et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology. 2006;44:675–684. doi: 10.1002/hep.21282. [DOI] [PubMed] [Google Scholar]
  • 16.Deguchi M, Yamashita N, Kagita M, Asari S, Iwatani Y, Tsuchida T, et al. Quantitation of hepatitis B surface antigen by an automated chemiluminescent microparticle immunoassay. J Virol Methods. 2004;115:217–222. doi: 10.1016/j.jviromet.2003.10.002. [DOI] [PubMed] [Google Scholar]
  • 17.Erhardt A, Ludwig A, Brunetto M, Boemmel F, Wolf E, Goebel T, et al. HBV genotypes are the strongest predictor of response to interferon-alfa treatment: multivariate evaluation in 1229 hepatitis B patients [abstract no. 883] Hepatology. 2008;48(Suppl 1):700A–701A. [Google Scholar]
  • 18.Heijtink RA, Snobl J, Kruining J, Kerkhof-Los C, Man RA, Janssen HL, Schalm SW. Quantitative measurement of HBeAg in chronic hepatitis B: a comparison between a radioimmunoassay, a fluorescence ELISA and a chemiluminescence ELISA. J Med Virol. 1995;47:245–250. doi: 10.1002/jmv.1890470310. [DOI] [PubMed] [Google Scholar]
  • 19.Mühlbacher A, Weber B, Bürgisser P, Eiras A, Cabrera J, Louisirirotchanakul S, et al. Multicenter study of a new fully automated HBsAg screening assay with enhanced sensitivity for the detection of HBV mutants. Med Microbiol Immunol. 2008;197:55–64. doi: 10.1007/s00430-007-0059-9. [DOI] [PubMed] [Google Scholar]
  • 20.Perrillo R, Mimms L, Schechtman K, Robbins D, Campbell C. Monitoring of antiviral therapy with quantitative evaluation of HBeAg: a comparison with HBV DNA testing. Hepatology. 1993;18:1306–1312. doi: 10.1002/hep.1840180604. [DOI] [PubMed] [Google Scholar]
  • 21.Coleman CF, Chen YC, Mushahwar IK. Immunoassaay detection of hepatitis B surface antigen mutants. J Med Virol. 1999;59:19–24. doi: 10.1002/(SICI)1096-9071(199909)59:1<19::AID-JMV4>3.0.CO;2-B. [DOI] [PubMed] [Google Scholar]
  • 22.Fried MW, Piratvisuth T, Lau GK, Marcellin P, Chow WC, Cooksley G, et al. HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B. Hepatology. 2008;47:428–434. doi: 10.1002/hep.22065. [DOI] [PubMed] [Google Scholar]
  • 23.Milich D, Liang TJ. Exploring the biological basis of hepatitis B e antigen in hepatitis B virus infection. Hepatology. 2003;38:1075–1086. doi: 10.1053/jhep.2003.50453. [DOI] [PubMed] [Google Scholar]
  • 24.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;116:829–834. doi: 10.1016/j.amjmed.2003.12.040. [DOI] [PubMed] [Google Scholar]
  • 25.Lin SM, Yu ML, Lee CM, Chien RN, Sheen IS, Chu CM, et al. Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma. J Hepatol. 2007;46:45–52. doi: 10.1016/j.jhep.2006.08.021. [DOI] [PubMed] [Google Scholar]
  • 26.Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, Haussinger D. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med. 1996;334:1422–1427. doi: 10.1056/NEJM199605303342202. [DOI] [PubMed] [Google Scholar]
  • 27.Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, et al. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002;347:168–174. doi: 10.1056/NEJMoa013215. [DOI] [PubMed] [Google Scholar]
  • 28.Maruyama T, McLachlan A, Iino S, Koike K, Kurokawa K, Milich DR. The serology of chronic hepatitis B infection revisited. J Clin Invest. 1993;91:2586–2595. doi: 10.1172/JCI116497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Wiseman E, Fraser M, Holden S, Glass A, Kidson B, Heron L, et al. Perinatal transmission of hepatitis B virus: viral load and HBeAg status are significant risk factors [abstract no. 827] Hepatology. 2008;48(Suppl 1):676A. [Google Scholar]
  • 30.Günther S, Fischer L, Pult I, Sterneck M, Will H. Naturally occurring variants of hepatitis B virus. Adv Virus Res. 1999;52:25–37. doi: 10.1016/S0065-3527(08)60298-5. [DOI] [PubMed] [Google Scholar]
  • 31.Locarnini S, McMillan J, Bartholomeusz A. The hepatitis B virus and common mutants. Semin Liver Dis. 2003;23:5–20. doi: 10.1055/s-2003-37587. [DOI] [PubMed] [Google Scholar]
  • 32.Lau GK, Piratvisuth T, Luo KX, Marcellin P, Thongsawat S, Cooksley G, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med. 2005;352:2682–2695. doi: 10.1056/NEJMoa043470. [DOI] [PubMed] [Google Scholar]
  • 33.Janssen HL, Zonneveld M, Senturk H, Zeuzem S, Akarca US, Cakaloglu Y, et al. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial. Lancet. 2005;365:123–129. doi: 10.1016/S0140-6736(05)17701-0. [DOI] [PubMed] [Google Scholar]
  • 34.Lok AS, Wu PC, Lai CL, Lau JY, Leung EK, Wong LS, et al. A controlled trial of interferon with or without prednisone priming for chronic hepatitis B. Gastroenterology. 1992;102:2091–2097. doi: 10.1016/0016-5085(92)90337-x. [DOI] [PubMed] [Google Scholar]
  • 35.Perrillo RP. Factors influencing response to interferon in chronic hepatitis B: implications for Asian and western populations. Hepatology. 1990;12:1433–1435. doi: 10.1002/hep.1840120626. [DOI] [PubMed] [Google Scholar]
  • 36.Burczynska B, Madalinski K, Pawlowska J, Woynarowski M, Socha J, Gerlich WH, et al. The value of quantitative measurement of HBeAg and HBsAg before interferon-alpha treatment of chronic hepatitis B in children. J Hepatol. 1994;21:1097–1102. doi: 10.1016/S0168-8278(05)80624-5. [DOI] [PubMed] [Google Scholar]
  • 37.Hayashi PH, Beames MP, Kuhns MC, Hoofnagle JH, Bisceglie AM. Use of quantitative assays for hepatitis B e antigen and IgM antibody to hepatitis B core antigen to monitor therapy in chronic hepatitis B. Am J Gastroenterol. 1996;91:2323–2328. [PubMed] [Google Scholar]
  • 38.Heijtink RA, Janssen HL, Hop WC, Osterhaus AD, Schalm SW. Interferon-alpha therapy in chronic hepatitis B: early monitoring of hepatitis B e antigen may help to decide whether to stop or to prolong therapy. J Viral Hepat. 2000;7:382–386. doi: 10.1046/j.1365-2893.2000.00246.x. [DOI] [PubMed] [Google Scholar]
  • 39.Buster EH, Flink HJ, Simsek H, Heathcote EJ, Sharmila S, Kitis G, et al. Early HBeAg loss during peginterferon alpha-2b therapy predicts HBsAg loss: results of a long-term follow-up study in chronic hepatitis B [abstract no. 928] Hepatology. 2008;48(Suppl 1):723A. doi: 10.1038/ajg.2009.371. [DOI] [PubMed] [Google Scholar]
  • 40.Strader DB, Wright T, Thomas DL, Seeff LB. AASLD practice guidelines: diagnosis, management, and treatment of Hepatitis C. Hepatology. 2004;39:1147–1171. doi: 10.1002/hep.20119. [DOI] [PubMed] [Google Scholar]
  • 41.Yee HS, Currie SL, Darling JM, Wright TL. Management and treatment of hepatitis C viral infection: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center program and the National Hepatitis C Program office. Am J Gastroenterol. 2006;101:2360–2378. doi: 10.1111/j.1572-0241.2006.00754.x. [DOI] [PubMed] [Google Scholar]
  • 42.Perrillo RP, Lai CL, Liaw YF, Dienstag JL, Schiff ER, Schalm SW, et al. Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B. Hepatology. 2002;36:186–194. doi: 10.1053/jhep.2002.34294. [DOI] [PubMed] [Google Scholar]
  • 43.Werle-Lapostolle B, Bowden S, Locarnini S, Wursthorn K, Petersen J, Lau G, et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology. 2004;126:1750–1758. doi: 10.1053/j.gastro.2004.03.018. [DOI] [PubMed] [Google Scholar]
  • 44.Thompson A, Shudo E, Ribeiro RM, Visvanathan K, Desmond P, Lau G, et al. New insights into HBV pathogenesis from kinetic analysis of HBeAg titre decay during potent antiviral therapy [abstract no 824] Hepatology. 2008;48(Suppl 1):674A–675A. [Google Scholar]
  • 45.Shin JW, Park NH, Jung SW, Kim BC, Kwon SH, Park JS, et al. Clinical significance of hepatitis B e antigen level measurement during long-term lamivudine therapy in chronic hepatitis B patients with e antigen positive. World J Gastroenterol. 2006;12:6693–6698. doi: 10.3748/wjg.v12.i41.6693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Park NH, Shin JW, Park JH, Bang SJ, Kim DH, Joo KR, Kim DH. Monitoring of HBeAg levels may help to predict the outcomes of lamivudine therapy for HBeAg positive chronic hepatitis B. J Viral Hepat. 2005;12:216–221. doi: 10.1111/j.1365-2893.2005.00602.x. [DOI] [PubMed] [Google Scholar]
  • 47.Yen YH, Lu SN, Chen CH, Wang JH, Wu CM, Hung CH, et al. Changes in serum hepatitis B e antigen (HBeAg) levels associated with the emergence of YMDD mutants in HBeAg non-seroconverted patients during lamivudine therapy. Liver Int. 2007;27:1349–1355. doi: 10.1111/j.1478-3231.2007.01609.x. [DOI] [PubMed] [Google Scholar]
  • 48.Laras A, Koskinas J, Dimou E, Kostamena A, Hadziyannis SJ. Intrahepatic levels and replicative activity of covalently closed circular hepatitis B virus DNA in chronically infected patients. Hepatology. 2006;44:694–702. doi: 10.1002/hep.21299. [DOI] [PubMed] [Google Scholar]
  • 49.Wong DK, Yuen MF, Tse E, Yuan H, Sum SS, Hui CK, et al. Detection of intrahepatic hepatitis B virus DNA and correlation with hepatic necroinflammation and fibrosis. J Clin Microbiol. 2004;42:3920–3924. doi: 10.1128/JCM.42.9.3920-3924.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Lu L, Ye D, Wang Y, Kwok A, Wong A, Yueng 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 [abstract no. 979] Hepatology. 2008;48(Suppl 1):746A. [Google Scholar]
  • 51.Manesis EK, Papatheodoridis GV, Hadziyannis E, Nastos T, Karayannis P. HBsAg serum levels correlate with total liver HBV DNA but not with cccDNA [abstract no. 147] Hepatology. 2008;48(Suppl 1):371A. [Google Scholar]
  • 52.Chu CJ, Hussain M, Lok AS. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology. 2002;36:1408–1415. doi: 10.1053/jhep.2002.36949. [DOI] [PubMed] [Google Scholar]
  • 53.Chen CH, Lee CM, Wang JH, Tung HD, Hung CH, Lu SN. Correlation of quantitative assay of hepatitis B surface antigen and HBV DNA levels in asymptomatic hepatitis B virus carriers. Eur J Gastroenterol Hepatol. 2004;16:1213–1218. doi: 10.1097/00042737-200411000-00021. [DOI] [PubMed] [Google Scholar]
  • 54.Su T, Hsu C, Liu C, Huang Y, Chen PJ, Kao JH. Quantitative HBsAg titer correlates well with HBV DNA in chronic hepatitis B patients [abstract no. 958] Hepatology. 2008;48(Suppl 1):736A–737A. [Google Scholar]
  • 55.Chan HL, Wong VW, Tse AM, Tse CH, Chim AM, Chan HY, et al. Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol. 2007;5:1462–1468. doi: 10.1016/j.cgh.2007.09.005. [DOI] [PubMed] [Google Scholar]
  • 56.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;123:1084–1089. doi: 10.1053/gast.2002.36026. [DOI] [PubMed] [Google Scholar]
  • 57.Fattovich G, Giustina G, Sanchez-Tapias J, Quero C, Mas A, Olivotto PG, et al. Delayed clearance of serum HBsAg in compensated cirrhosis B: relation to interferon alpha therapy and disease prognosis. European Concerted Action on Viral Hepatitis (EUROHEP) Am J Gastroenterol. 1998;93:896–900. doi: 10.1111/j.1572-0241.1998.00272.x. [DOI] [PubMed] [Google Scholar]
  • 58.Hsu YS, Chien RN, Yeh CT, Sheen IS, Chiou HY, Chu CM, Liaw YF. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology. 2002;35:1522–1527. doi: 10.1053/jhep.2002.33638. [DOI] [PubMed] [Google Scholar]
  • 59.Mason AL, Xu L, Guo L, Kuhns M, Perrillo RP. Molecular basis for persistent hepatitis B virus infection in the liver after clearance of serum hepatitis B surface antigen. Hepatology. 1998;27:1736–1742. doi: 10.1002/hep.510270638. [DOI] [PubMed] [Google Scholar]
  • 60.Lai CL, Dienstag J, Schiff E, Leung NW, Atkins M, Hunt C, et al. Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B. Clin Infect Dis. 2003;36:687–696. doi: 10.1086/368083. [DOI] [PubMed] [Google Scholar]
  • 61.Buster EH, Flink HJ, Cakaloglu Y, Simon K, Trojan J, Tabak F, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology. 2008;135:459–467. doi: 10.1053/j.gastro.2008.05.031. [DOI] [PubMed] [Google Scholar]
  • 62.Brunetto MR, Bonino F, Marcellin P, Button P, Batrla R. Kinetics of HBsAg decline in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a according to genotype and its association with sustained HBsAg clearance 4 years post-treatment [abstract no. 965] Hepatology. 2008;48(Suppl 1):740A. [Google Scholar]
  • 63.Brunetto MR, Cavallone D, Moriconi F, Colombatto P, Moscato G, Maina A, et al. Kinetics of HBsAg decline during and following treatment of CHB: Early and rapid HBsAg decline during peginterferon alfa-2a is predictive of HBsAg clearance [abstract no. 917] Hepatology. 2008;48(Suppl 1):717A. [Google Scholar]
  • 64.Hou J, Sun J, Xie Q, Li X, Zhang J, Wang Y, Lai JY, et al. Efficacy and safety of peginterferon alfa-2a versus adefovir dipivoxil (ADV) in treating lamivudine resistant HBeAg positive CHB: an interim analysis of a prospective randomised study [abstract no. 978] Hepatology. 2008;48(Suppl 1):745A. [Google Scholar]
  • 65.Lau G, Marcellin P, Brunetto MR, Piratvisuth T, Kapprell H, Button P, Batrla R. On-treatment HBsAg decline during peginterferon alfa-2a (40KD) ± lamivudine in patients with HBeAg-positive CHB as a potential predictor of durable off-treatment response [abstract no. 910] Hepatology. 2008;48(Suppl 1):714A. [Google Scholar]
  • 66.Manesis EK, Hadziyannis ES, Angelopoulou OP, Hadziyannis SJ. Prediction of treatment-related HBsAg loss in HBeAg-negative chronic hepatitis B: a clue from serum HBsAg levels. Antivir Ther. 2007;12:73–82. [PubMed] [Google Scholar]
  • 67.Moucari R, Mackiewicz V, Lada O, Ripault MP, Castelnau C, Martinot-Peignoux M, et al. Early serum HBsAg drop: a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology. 2009;49:1151–1157. doi: 10.1002/hep.22744. [DOI] [PubMed] [Google Scholar]
  • 68.Rijckborst V, Borg MJ, Akarca US, Grima P, Flisiak R, Vafiadis-Zouboulis I, et al. Early reduction of serum HBsAg levels in HBeAg-negative chronic hepatitis B patients achieving sustained virological response after peginterferon alfa-2a ± ribavirin treatment [abstract no. 986] Hepatology. 2008;48(Suppl 1):749A–750A. [Google Scholar]
  • 69.Takkenberg B, Zaaijer HL, Weegink C, Terpstra V, Dijkgraaf M, Jansen P, et al. High rate of HBsAg loss and HBsAg seroconversion in chronic hepatitis B patients on combination therapy with peginterferon alfa-2a (Pegasys) and adefovir (Hepsera): HBsAg titer predicts HBsAg loss or seroconversion [abstract no. LB14] Hepatology. 2008;48(Suppl 1):1026A. [Google Scholar]
  • 70.Marcellin P, Brunetto MR, Bonino F, Hadziyannis E, Kapprell H, McCloud P, et al. In patients with HBeAg-negative chronic hepatitis B, HBsAg serum levels early during treatment with peginterferon alfa-2a predict HBsAg clearance 4 years post-treatment [abstract no. 919] Hepatology. 2008;48(Suppl 1):718A–719A. [Google Scholar]
  • 71.Tsiang M, Rooney JF, Toole JJ, Gibbs CS. Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy. Hepatology. 1999;29:1863–1869. doi: 10.1002/hep.510290626. [DOI] [PubMed] [Google Scholar]
  • 72.Kohmoto M, Enomoto M, Tamori A, Habu D, Takeda T, Kawada N, et al. Quantitative detection of hepatitis B surface antigen by chemiluminescent microparticle immunoassay during lamivudine treatment of chronic hepatitis B virus carriers. J Med Virol. 2005;75:235–239. doi: 10.1002/jmv.20262. [DOI] [PubMed] [Google Scholar]
  • 73.Galli C, Orlandini E, Penzo L, Badiale R, Caltran G, Valverde S, Gessoni G. 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;80:974–979. doi: 10.1002/jmv.21179. [DOI] [PubMed] [Google Scholar]
  • 74.Kobayashi M, Suzuki F, Akuta N, Hosaka T, Sezaki H, Yatsuji H, et al. Loss of hepatitis B surface antigen from the serum of patients with chronic hepatitis treated with lamivudine. J Med Virol. 2007;79:1472–1477. doi: 10.1002/jmv.20994. [DOI] [PubMed] [Google Scholar]

Articles from Hepatology International are provided here courtesy of Asian Pacific Association for the Study of the Liver

RESOURCES