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Epidemiology and Diagnosis of Hepatitis B in the Mediterranean Region and Elsewhere

  • Nurdan TözünEmail author
  • Özdal Ersoy
  • Fatih Eren
  • Veysel Tahan
Conference paper
Part of the NATO Science for Peace and Security Series A: Chemistry and Biology book series (NAPSA)

Abstract

After cancer, viral infections constitute a great threat to human health throughout the world and among these viral hepatitis constitutes one of the most important public threats in the world. Despite considerable advances in medical technology and attempts to eradicate the diseases, viral hepatitis still remain as major public health problem with their high morbidity and mortality in the Mediterranean, Eastern Europe, Middle East and elsewhere. Uncontrolled migratory flow from developing countries to regions of low endemicity gave rise to changes not only in the prevalence of viral infection but also the genotype, clinical course and modes of transmission. Among several viruses which may affect the liver those which constitute important public health problems are hepatitis A, B, C, D, and E. All of these viruses can cause an acute disease with symptoms lasting several weeks however HBV can cause asymptomatic infection which can silently progress to chronic infection in which the patient never gets rid of the virus and many years later develops cirrhosis of the liver or liver cancer. Of the two billion people who have been infected with HBV, more than 350 million have chronic (lifelong) infections. In this chapter, we reviewed the present situation, epidemiology, clinical presentation, prevention, diagnostic techniques and the universal importance of Hepatitis B.

Keywords

Hepatitis B infection hepatocellular carcinoma, cirrhosis epidemiology HBV 

Abbreviations

ALT

Alanine aminotransferase

anti-HBc

Antibody to hepatitis B virus core antigen

anti-Hbe

Antibody to hepatitis B virus e antigen

bps

Bits per second

DNA

Deoxyribonucleic acid

EU

European Union

HCW

Health care workers

HBV

Hepatitis B virus

HCC

Hepatocellular carcinoma

anti-HBs

Hepatitis B surface antibody

HbeAg

Hepatitis B virus e antigen

HbsAg

Hepatitis B virus surface antigen

HIV

Human immune deficiency virus

RNA

Ribonucleic acid

USSR

Union of Soviet Socialist Republics

WHO

World Health Organization

References

  1. Alter MJ (2003) Epidemiology of hepatitis B in Europe and worldwide. J Hepatol 39:64–69CrossRefGoogle Scholar
  2. Alter MJ, Margolis HS (1990) The emergence of hepatitis B as a sexually transmitted disease. Med Clin N Am 74:1529–1541PubMedGoogle Scholar
  3. Alter HJ, Seeff LB, Kaplan PM, McAuliffe VJ, Wright EC, Gerin JL et al (1976) Type B hepatitis: the infectivity of blood positive for e antigen and DNA polymerase after accidental needlestick exposure. N Engl J Med 295:909–913PubMedCrossRefGoogle Scholar
  4. Alter HJ, Purcell RH, Gerin JL, London WT, Kaplan PM, McAuliffe VJ et al (1977) Transmission of hepatitis B to chimpanzees by hepatitis B surface antigen-positive saliva and semen. Infect Immun 16:928–933PubMedGoogle Scholar
  5. Alter MJ, Ahtone J, Maynard JE (1983) Multiple-dose vial associated with transmission of hepatitis B virus in a hemodialysis unit. Ann Intern Med 99:330–333PubMedGoogle Scholar
  6. Amato-Gauci A, Ammon A (2007) ECDC to launch first report on communicable diseases epidemiology in the European Union. Euro Surveill. 12(6):E070607.2Google Scholar
  7. Attila L (2006) Nucleic acid testing for human disease by Taylor & Francis group, chapter 2, pp 19–65Google Scholar
  8. Bancroft WH, Snitbhan R, Scott RM, Tingpalapong M, Watson WT, Tanticharoenyos P, et al (1977) Transmission of hepatitis B virus to gibbons by exposure to human saliva containing hepatitis B surface antigen. J Infect Dis 135:79–85PubMedCrossRefGoogle Scholar
  9. Barlet V, Cohard M, Thelu MA, Chaix MJ, Baccard C, Zarski JP, Seigneurin JM (Sep 1994) Quantitative detection of hepatitis B virus DNA in serum using chemiluminescence: comparison with radioactive solution hybridization assay. J Virol Methods 49(2):141–151PubMedCrossRefGoogle Scholar
  10. Benner SA, Steven A, Sismour M (July 2005) Synthetic biology. Nat Rev Gen 6:533–543CrossRefGoogle Scholar
  11. Bernard PS, Wittwer CT (Aug 2002) Real-time PCR technology for cancer diagnostics. Clin Chem 48(8):1178–1185 (Review)Google Scholar
  12. Brechtbuehl K, Whalley SA, Dusheiko GM, Saunders NA (Apr 2001) A rapid real-time quantitative polymerase chain reaction for hepatitis B virus. J Virol Methods 93(1–2):105–113PubMedCrossRefGoogle Scholar
  13. Brunetto MR, Moriconi F, Bonino F, Lau GK, Farci P, Yurdaydin C, Piratvisuth T, Luo K, Wang Y, Hadziyannis S, Wolf E, McCloud P, Batrla R, Marcellin P (Apr 2009) Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Hepatology 49(4):1141–1150PubMedCrossRefGoogle Scholar
  14. Chan HL, Hui AY, Wong ML, Tse AM, Hung LC, Wong VW, Sung JJ (2004) Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Gut 53:1494–1498PubMedCrossRefGoogle Scholar
  15. Chan HL, Wong VW, Tse AM, Tse CH, Chim AM, Chan HY, Wong GL, Sung JJ (Dec 2007) Serum hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol 5(12):1462–1468PubMedCrossRefGoogle Scholar
  16. Chang MH (2009) Cancer prevention by vaccination against hepatitis B. Recent Results Cancer Res 181:85–94 (Review)Google Scholar
  17. Chevaliez S, Pawlotsky JM (7 May 2007) Hepatitis C virus: virology, diagnosis and management of antiviral therapy. World J Gastroenterol 13(17):2461–2466 (Review)Google Scholar
  18. Chevaliez S, Pawlotsky JM (Jan–Mar 2009) Virological techniques for the diagnosis and monitoring of hepatitis B and C. Ann Hepatol 8(1):7–12 (Review)Google Scholar
  19. Chu CJ, Keeffe EB, Han SH, Perrillo RP, Min AD, Soldevila-Pico C, Carey W, Brown RS Jr, Luketic VA, Terrault N, Lok AS (2003) Hepatitis B virus genotypes in the United States: results of a nationwide survey. Gastroenterology 125:444PubMedCrossRefGoogle Scholar
  20. Da Villa G, Piccinino F, Scolastico C, Fusco M, Piccinino R, Sepe A (1998) Long-term epidemiological survey of hepatitis B virus infection in a hyperendemic area (Afragola, Southern Italy): results of a pilot vaccination project. Res Virol 149:263–270PubMedCrossRefGoogle Scholar
  21. Dal-Re R, Aguilar L, Coronel P (1991) Current prevalence of hepatitis B, A and C in a healthy Spanish population. A seroepidemiological study. Infection 19:409–413PubMedCrossRefGoogle Scholar
  22. Degertekin H, Tuzcu A, Yalcin K (2000) Horizontal transmission of HBV infection among students in Turkey. Public Health 114:411–412PubMedCrossRefGoogle Scholar
  23. EASL (2009) EASL clinical practice guidelines: management of chronic hepatitis B. J Hepatol 50:227–242CrossRefGoogle Scholar
  24. Esteban JI, Sauleda S, Quer J (2008) The changing epidemiology of hepatitis C infection in Europe. J Hepatol 48:148–162PubMedCrossRefGoogle Scholar
  25. Fattovich G (2003) Natural history and prognosis of hepatitis B. Semin Liver Dis 23:47–68PubMedCrossRefGoogle Scholar
  26. Fattovich G, Pantalena M, Zagni I, Realdi G, Schalm SW, Christensen E (2002) Effect of hepatitis B and C virus infections on the natural history of compensated cirrhosis: a cohort study of 297 patients. Am J Gastroenterol 97:2886–2895PubMedCrossRefGoogle Scholar
  27. Fattovich G, Bortolotti F, Donato F (2008) Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 48:335–352PubMedCrossRefGoogle Scholar
  28. Fung SK, Lok ASF (2004) Treatment of chronic hepatitis B: who to treat, what to use, and for how long? Clin Gastroenterol Hepatol 2:839–848PubMedCrossRefGoogle Scholar
  29. Gauthier J, Bourne EJ, Lutz MW, Crowther LM, Dienstag JL, Brown NA, Condreay LD (Dec 1999) Quantitation of hepatitis B viremia and emergence of YMDD variants in patients with chronic hepatitis B treated with lamivudine. J Infect Dis 180(6):1757–1762PubMedCrossRefGoogle Scholar
  30. Gibb R, Nimmo GR, O’Loughlin P, Lowe P, Drummond D (2007) Detection of HBsAg mutants in a population with a low prevalence of hepatitis B virus infection. J Med Virol 79:351–355PubMedCrossRefGoogle Scholar
  31. Guidotti LG, Rochford R, Chung J, Shapiro M, Purcell R, Chisari FV (1999) Viral clearance without destruction of infected cells during acute HBV infection. Science 284:825–829PubMedCrossRefGoogle Scholar
  32. Hendricks DA, Stowe BJ, Hoo BS, Kolberg J, Irvine BD, Neuwald PD, Urdea MS (Nov 1995) Perrillo RP Quantitation of HBV DNA in human serum using a branched DNA (bDNA) signal amplification assay. Am J Clin Pathol 104(5):537–546PubMedGoogle Scholar
  33. Ho SK, Chan TM, Cheng IK, Lai KN (Aug 1999) Comparison of the second-generation digene hybrid capture assay with the branched-DNA assay for measurement of hepatitis B virus DNA in serum. J Clin Microbiol 37(8):2461–2465PubMedGoogle Scholar
  34. Hsieh CC, Tzonou A, Zavitsanos X, Kaklamani E, Lan SJ, Trichopoulos D (1992) Age at first establishment of chronic hepatitis B virus infection and hepatocellular carcinoma risk. A birth order study. Am J Epidemiol 136:1115–1121PubMedGoogle Scholar
  35. Hui AY, Chan HL, Leung NW, Hung LC, Chan FK, Sung JJ (2002) Survival and prognostic indicators in patients with hepatitis B virus-related cirrhosis after onset of hepatic decompensation. J Clin Gastroenterol 34:569–572PubMedCrossRefGoogle Scholar
  36. Hui CK, Leung N, Yuen ST, Zhang HY, Leung KW, Lu L et al (2007) Natural history and disease progression in Chinese chronic hepatitis B patients in immune-tolerant phase. Hepatology 46:395–401PubMedCrossRefGoogle Scholar
  37. Hutin YJ, Harpaz R, Drobeniuc J, Melnic A, Ray C, Favorov M et al (1999) Injections given in healthcare settings as a major source of acute hepatitis B in Moldova. Int J Epidemiol 28:782–786PubMedCrossRefGoogle Scholar
  38. Kane A, Lloyd J, Zaffran M et al (1999) Transmission of hepatitis B, hepatitis C and human immunodeficiency viruses through unsafe injections in the developing world: model- based regional estimates. Bull World Health Organ 77(10):801–807PubMedGoogle Scholar
  39. Kao JH (2007) Role of viral factors in the natural course and therapy of chronic hepatitis B. Hepatol Int 1:415–430PubMedCrossRefGoogle Scholar
  40. Kao JH, Chen PJ, Lai MY, Chen DS (2000) Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 118:554–559PubMedCrossRefGoogle Scholar
  41. Kent GB, Brondum J, Keenlyside RA, LaFazia LM, Scott HD (1988) A large outbreak of acupuncture- associated hepatitis B. Am J Epidemiol 127:591–598PubMedGoogle Scholar
  42. Kyriakis KP, Foudoulaki LE, Papoulia EI, Sofroniadou KE (2000) Seroprevalence of hepatitis B surface antigen (HBsAg) among first-time and sporadic blood donors in Greece: 1991–1996. Transfusion Med 10:175–180CrossRefGoogle Scholar
  43. Lavanchy D (2004) Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepatol 11:97–107CrossRefGoogle Scholar
  44. Lee WM (1997) Hepatitis B virus infection. N Engl J Med 337(24):1733–1745PubMedCrossRefGoogle Scholar
  45. Liaw JF, Chu CM (2009) Hepatitis B virus infection. Lancet 373:582–592PubMedCrossRefGoogle Scholar
  46. Limentani AE, Elliott LM (1979) An outbreak of hepatitis B from tattooing. Lancet 2:86–88PubMedCrossRefGoogle Scholar
  47. Lin HH, Kao JH, Chang TC, Hsu HY, Chen DS (2003) Secular trend of age-specific prevalence of hepatitis B surface and e antigenemia in pregnant women in Taiwan. J Med Virol 69:466–470PubMedCrossRefGoogle Scholar
  48. Lionis C, Koulentaki M, Biziagos E, Kouroumalis E (1997) Current prevalence of hepatitis A, B and C in a well-defined area in rural Crete, Greece. J Viral Hepatitis 4:55–61CrossRefGoogle Scholar
  49. Loeb KR, Jerome KR, Goddard J, Huang M, Cent A, Corey L (Sep 2000) High-throughput quantitative analysis of hepatitis B virus DNA in serum using the TaqMan fluorogenic detection system. Hepatology 32(3):626–629PubMedCrossRefGoogle Scholar
  50. Lok AS (2002) Chronic hepatitis B. N Engl J Med 346(22):1682–1683PubMedCrossRefGoogle Scholar
  51. Lok AS, McMahon BJ (2007) Chronic hepatitis B. Hepatology 45:507–539PubMedCrossRefGoogle Scholar
  52. Lok AS, Heathcote EJ, Hoofnagle JH (2001) Management of hepatitis B: 2000 – summary of a workshop. Gastroenterology 120(7):1828–1853PubMedCrossRefGoogle Scholar
  53. Lopez VA, Bourne EJ, Lutz MW, Condreay LD (Jun 2002) Assessment of the COBAS Amplicor HBV Monitor Test for quantitation of serum hepatitis B virus DNA levels. J Clin Microbiol 40(6):1972–1976PubMedCrossRefGoogle Scholar
  54. Lorinez A (2006) Nucleic acid testing for human disease in nucleic acid techonology. CRC Press/Taylor & Francis, Boca Raton, FL co. 616.075 LOR. (ISSN 1-57444-543-X)Google Scholar
  55. Mackay IM (2004) Real-Time PCR in the microbiology laboratory. Clin Microbiol Infect 10:190–212PubMedCrossRefGoogle Scholar
  56. Magdzik W (2000) Hepatitis B epidemiology in Poland, Central and Eastern Europe and the newly independent states. Vaccine 18:S13–S16PubMedCrossRefGoogle Scholar
  57. Mahoney FJ (1999) Update on diagnosis, management, and prevention of hepatitis B virus infection. Clin Microbiol Rev 12(2):351–366PubMedGoogle Scholar
  58. Maini MK, Boni C, Lee CK et al (2000) The role of virus-specifi c CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. J Exp Med 191:1269–1280PubMedCrossRefGoogle Scholar
  59. Manesis EK (2006) HBeAg-negative chronic hepatitis B: from obscurity to prominence. J Hepatol 45:343–346PubMedCrossRefGoogle Scholar
  60. Marin IJ, Poljak M, Seme K, Meglic-Volkar J, Maticic M, Lesnicar G, Brinovec V (Feb 2001) Comparative evaluation of semiautomated COBAS AMPLICOR hepatitis B virus (HBV) monitor test and manual microwell plate-based AMPLICOR HBV MONITOR test. J Clin Microbiol 39(2):758–761PubMedCrossRefGoogle Scholar
  61. Marion SA, Pastore MT, Pi DW, Mathias RG (1994) Longterm follow-up of hepatitis B vaccine in infants of carrier mothers. Am J Epidemiol 140:734–746PubMedGoogle Scholar
  62. Martinot-Peignoux M, Boyer N, Colombat M, Akremi R, Pham BN, Ollivier S et al (2002) Serum hepatitis B virus DNA levels and liver histology in inactive HBsAg carriers. J Hepatol 36:543–546PubMedCrossRefGoogle Scholar
  63. Mazokopakis E, Vlachonikolis J, Philalithis A, Lionis C (2000) Seroprevalence of hepatitis A, B and C markers in Greek warship personnel. Eur J Epidemiol 16:1069–1072PubMedCrossRefGoogle Scholar
  64. McKnight CA, Des Jarlais DC, Perlis T, Eigo K (2007) Syringe exchange programs—United States, 2005. MMWR Morb Mortal Wkly Rep 56:1164–67Google Scholar
  65. Mele A, Tancredi F, Romano L, Giuseppone A, Colucci M, Sangiuolo A, Lecce R, Adamo B, Tosti ME, Taliani G, Zanetti AR (2001) Effectiveness of hepatitis B vaccination in babies born to hepatitis B surface antigen-positive mothers in Italy. J Infect Dis 184:905–908PubMedCrossRefGoogle Scholar
  66. Muhlbacher A, Weber B, Burgisser P, Eiras A, Cabrera J, Louisirirotchanakul S, Tiller FW et al (2008) Multicenter study of a new fully automated HBsAg screening assay with enhanced sensitivity for the detection of HBV mutants. Med Microbiol Immunol 197:55–64PubMedCrossRefGoogle Scholar
  67. Murray JM, Wieland SF, Purcell RH, Chisari FV (2005) Dynamics of hepatitis B virus clearance in chimpanzees. Proc Natl Acad Sci USA 102:17780–17785PubMedCrossRefGoogle Scholar
  68. Ni Y-H, Chang M-H, Huang L-M, Chen HL, Hsu HY, Chiu TY et al (2001) Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination. Ann Intern Med 135:796–800PubMedGoogle Scholar
  69. Ni YH, Chang MH, Wang KJ et al (2004) Clinical relevance of hepatitis B virus genotype in children with chronic infection and hepatocellular carcinoma. Gastroenterology 127:1733–1738PubMedCrossRefGoogle Scholar
  70. Ozaras R, Tabak F, Tahan V, Ozturk R, Akin H, Mert A, Senturk H (2008) Correlation of quantitative assay of HBsAg and HBV DNA levels during chronic HBV treatment. Dig Dis Sci 53:2995–2998PubMedCrossRefGoogle Scholar
  71. Palumbo E, Scotto G, Cibelli D, Faleo G, Saracin A, Angarano G (2008) Immigration and hepatitis B virus: epidemiological, clinical and therapeutic aspects. La Revue de Santé de la Méditerranée orientale 14(4):784–790Google Scholar
  72. Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94(2):153–156PubMedCrossRefGoogle Scholar
  73. Pawlotsky JM.Molecular diagnosis of viral hepatitis. Gastroenterology 2002;122:1554-1568Google Scholar
  74. Perz JF, Elm JL Jr, Fiore AE, Huggler JI, Kuhnert WL, Effler PV (2006a) Near elimination of hepatitis B virus infections among Hawaii elementary school children after universal hepatitis B vaccination. Pediatrics 118:1403PubMedCrossRefGoogle Scholar
  75. Perz JF, Armstrong GL, Farrington LA et al (2006b) The contribution of hepatitis B and hepatitis C virus infection to cirrhosis and primary liver cancer worldwide. J Hepatol 45:529–538PubMedCrossRefGoogle Scholar
  76. Ronsin C, Pillet A, Bali C, Denoyel GA (Apr 2006) Evaluation of the COBAS Ampli Prep-total nucleic acid isolation-COBAS TaqMan hepatitis B virus (HBV) quantitative test and comparison to the VERSANT HBV DNA 3.0 assay. J Clin Microbiol 44(4):1390–1399PubMedCrossRefGoogle Scholar
  77. Sakugawa H, Kobashigawa K, Nakayoshi T, Yamashiro T, Maeshiro T, Tomimori K, Kinjo F, Saito A, Mukaide M (Aug 2003) Monitoring low level hepatitis B virus by a newly developed sensitive test. Hepatol Res 26(4):281–286PubMedCrossRefGoogle Scholar
  78. Schmunis GA, Zicker F, Cruz JR, Cuchi P (2001) Safety of blood supply for infectious diseases in Latin American countries, 1994–1997. Am J Trop Med Hyg 65(6):924–930PubMedGoogle Scholar
  79. Simonsen L, Kane A, Lloyd J, Zaffran M, Kane M (1999) Unsafe injections in the developing world and transmission of bloodborne pathogens: a review. Bull World Health Organ 77(10):789–800PubMedGoogle Scholar
  80. Stelzl E, Muller Z, Marth E, Kessler HH (Jun 2004) Rapid quantification of hepatitis B virus DNA by automated sample preparation and real-time PCR. J Clin Microbiol 42(6):2445–2449PubMedCrossRefGoogle Scholar
  81. Summers J, Mason WS (1982) Replication of the genome of a hepatitis B-like virus by reverse transcription of an RNA intermediate. Cell 29:403–415PubMedCrossRefGoogle Scholar
  82. Toy M, Önder FM, Wormann T, Richardus JH, Schalm S, İdilman H, Değertekin H, Yurdaydın C (2009) Pevalance of hepatitis B in turkey: meta-analysis -abstract. 7th National Meeting of Hepatology, Izmir,Turkey, 10–14 June 2009 (abstract book)Google Scholar
  83. Ture Ozdemir F, Duman D, Ertem D, Avsar E, Ozdogan O, Eren F, Kalaycı C, Aslan N, Bozdayı AM, Tozun N (Dec 2005) Determination of hepatitis B genotypes in patients with chronic hepatitis B virus infection in Turkey. Turk J Gastroenterol 16(4):183–187Google Scholar
  84. Weber B, Van der Taelem-Brule N, Berger A, Simon F, Geudin M, Ritter J (2006) Evaluation of a new automated assay for hepatitis B surface antigen (HBsAg) detection Vidas HBsAg ultra. J Virol Methods 135:109–117PubMedCrossRefGoogle Scholar
  85. Wheeley SM, Boxall EH, Tarlow MJ, Gatrad AR, Anderson J, Bissenden J, Chin KC, Mayne A (1990) Hepatitis B vaccine in the prevention of perinatally transmitted hepatitis B virus infection: final report on a west midlands pilot study. J MedVirol 30:113–116Google Scholar
  86. Wong ML, Medrano JF (July 2005) Real-time PCR for mRNA quantitation. Biotechniques 39(1):75–85 (Review)Google Scholar
  87. Wong VCW, Ip HMH, Reesink HW, Kuhns MC (1984) Prevention of the HBsAg-carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis vaccine and hepatitis-B immunoglobulin. Lancet 8383:921–926CrossRefGoogle Scholar
  88. World Health Organization (2000) Hepatitis B. World Health Organization Fact Sheet 204 (Revised October 2000). WHO Web site. 2000. http://who.int/inf-fs/en/fact204.html
  89. Worman HJ (Aug 1997) Molecular biological methods in diagnosis and treatment of liver diseases. Clin Chem 43(8 Pt 2):1476–1486PubMedGoogle Scholar
  90. Xu ZY, Duan SC, Margolis HS (1995) Long-term efficacy of active postexposure immunization of infants for prevention of hepatitis B virus infection. United States-people’s republic of China study group on hepatitis B. J Infect Dis 171:54–60PubMedCrossRefGoogle Scholar
  91. Yao JD, Beld MG, Oon LL, Sherlock CH, Germer J, Menting S, Se Thoe SY, Merrick L, Ziermann R, Surtihadi J, Hnatyszyn HJ (Feb 2004) Multicenter evaluation of the VERSANT hepatitis B virus DNA 3.0 assay. J Clin Microbiol 42(2):800–806PubMedCrossRefGoogle Scholar
  92. Yuen MF, Sablon E, Tanaka Y, Kato T, Mizokami M, Doutreloigne J, Yuan HJ, Wong DK, Sum SM, Lai CL (2004) Epidemiological study of hepatitis B virus genotypes, core promoter and precore mutations of chronic hepatitis B infection in Hong Kong. J Hepatol 41:119–125PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Nurdan Tözün
    • 1
    Email author
  • Özdal Ersoy
    • 2
  • Fatih Eren
    • 3
  • Veysel Tahan
    • 4
  1. 1.Department of Gastroenterology, School of MedicineAcıbadem UniversityIstanbulTurkey
  2. 2.Gastroenterology DepartmentAcıbadem Kozyatagi HospitalIstanbulTurkey
  3. 3.Molecular Biology Department, Institute of GastroenterologyMarmara UniversityIstanbulTurkey
  4. 4.Department of Pathology and Laboratory MedicineHospital of the University of PennsylvaniaPittsburghUSA

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