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

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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.

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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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  3. Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, et al. 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

    Article  PubMed  CAS  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

    Article  PubMed  Google Scholar 

  5. Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45:507–539

    Article  PubMed  CAS  Google Scholar 

  6. Chang TT, Gish RG, de 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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  9. Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, Krastev Z, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med 2008;359:2442–2455

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  12. Heijtink RA, Kruining J, Honkoop P, Kuhns MC, Hop WC, Osterhaus AD, et al. Serum HBeAg quantitation during antiviral therapy for chronic hepatitis B. J Med Virol 1997;53:282–287

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  17. Erhardt A, Ludwig A, Brunetto M, Van 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, de Man RA, Janssen HL, et al. 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

    Article  PubMed  CAS  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

    Article  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

    Article  PubMed  CAS  Google Scholar 

  21. Coleman CF, Chen YC, Mushahwar IK. Immunoassaay detection of hepatitis B surface antigen mutants. J Med Virol 1999;59:19–24

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  26. Niederau C, Heintges T, Lange S, Goldmann G, Niederau CM, Mohr L, et al. Long-term follow-up of HBeAg-positive patients treated with interferon alfa for chronic hepatitis B. N Engl J Med 1996;334:1422–1427

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  Google Scholar 

  31. Locarnini S, McMillan J, Bartholomeusz A. The hepatitis B virus and common mutants. Semin Liver Dis 2003;23:5–20

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  33. Janssen HL, van 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

    Article  PubMed  CAS  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

    PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  37. Hayashi PH, Beames MP, Kuhns MC, Hoofnagle JH, Di 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  CAS  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

    Article  PubMed  CAS  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

    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

    Article  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

    Article  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    PubMed  CAS  Google Scholar 

  46. Park NH, Shin JW, Park JH, Bang SJ, Kim DH, Joo KR, et al. 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

    Article  PubMed  CAS  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

    PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  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

    Article  PubMed  CAS  Google Scholar 

  58. Hsu YS, Chien RN, Yeh CT, Sheen IS, Chiou HY, Chu CM, et al. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology 2002;35:1522–1527

    Article  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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, 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, et al. 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  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

  73. Galli C, Orlandini E, Penzo L, Badiale R, Caltran G, Valverde S, 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;80:974–979

    Article  PubMed  CAS  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

    Article  PubMed  CAS  Google Scholar 

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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.

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Authors and Affiliations

  1. Gastroenterology Department, St. Vincent’s Hospital, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia

    Tin Nguyen

  2. Gastroenterology Department, St. Vincent’s Hospital, Melbourne, VIC, Australia

    Paul Desmond

  3. Head, Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia

    Stephen Locarnini

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Nguyen, T., Desmond, P. & Locarnini, S. The role of quantitative hepatitis B serology in the natural history and management of chronic hepatitis B. Hepatol Int 3 (Suppl 1), 5–15 (2009). https://doi.org/10.1007/s12072-009-9149-7

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