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Global Epidemiology of Hepatitis B Virus Infection

Chapter
Part of the Molecular and Translational Medicine book series (MOLEMED)

Abstract

Hepatitis B is one of the major diseases of mankind, estimated to cause about 800,000 deaths per year mostly from liver cancer and cirrhosis. The history of the epidemiology of hepatitis B represents a landmark in the general understanding of viral infections, their distributions and their outcomes. In 2010 and 2014 resolutions of the World Health Assembly, have acknowledged at the political level that viral hepatitis is a global public health problem, ranking HBV as the 15th cause of death in all cause global mortality. The global prevalence of chronic carriage varies between 0.1 and more than 20 %. Approximately 15–40 % of chronically infected patients will develop liver cirrhosis, liver failure, or hepatocellular carcinoma and 15–25 % will ultimately die. As of today (2014), approximately 2 billion people have been infected worldwide and 240 million are chronic carriers of HBV. This represents a decrease of 31 % in HBsAg prevalence as compared to the former published figures of 350–400 million. The decrease is mainly observed in younger age groups and it is likely due to the availability of better population based data, population wide vaccination against hepatitis B in newborns, young children and adolescents, improved screening of blood products and improved safe injection procedures. However, globally an increase in both genders was observed between the 1990s and 2005 causing a change from low to a low-intermediate endemicity level in young men. It is important to note the great impact of routine infant and childhood hepatitis B immunization programs, which have caused a dramatic reduction of HBsAg carriage in immunized cohorts of children, and have led to significant decreases in HBV transmission and the occurrence of related cirrhosis and liver cancer in various populations. However, the work is not finished and a lot remains to be done to prevent new HBV infections and to cure chronically infected individuals.

Keywords

Viral hepatitis B HBV Epidemiology Prevalence Prevention Liver cancer HCC Cirrhosis 

References

  1. 1.
    Blumberg BS, Alter HJ, Visnich S. A “new” antigen in leukemia sera. JAMA. 1965;191:541–6.PubMedGoogle Scholar
  2. 2.
    Purcell RH. The discovery of the hepatitis viruses. Gastroenterology. 1993;104(4):955–63.PubMedGoogle Scholar
  3. 3.
    Alter HJ. The unexpected outcomes of medical research: serendipity and the Australia antigen. J Hepatol. 2003;39(2):149–52.PubMedGoogle Scholar
  4. 4.
    Feinstone SM, Kapikian AZ, Purcell RH. Hepatitis A: detection by immune electron microscopy of a viruslike antigen associated with acute illness. Science. 1973;182(4116):1026–8.PubMedGoogle Scholar
  5. 5.
    Rizzetto M, Canese MG, Arico S, et al. Immunofluorescence detection of new antigen-antibody system (delta/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers. Gut. 1977;18(12):997–1003.PubMedCentralPubMedGoogle Scholar
  6. 6.
    Reyes GR, Purdy MA, Kim JP, et al. Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science. 1990;247(4948):1335–9.PubMedGoogle Scholar
  7. 7.
    Beasley RP. Hepatitis B virus. The major etiology of hepatocellular carcinoma. Cancer. 1988;61(10):1942–56.PubMedGoogle Scholar
  8. 8.
    Lok AS. Chronic hepatitis B. N Engl J Med. 2002;346(22):1682–3.PubMedGoogle Scholar
  9. 9.
    de Franchis R, Hadengue A, Lau G, et al. EASL International Consensus Conference on Hepatitis B 13–14 September. 2002 Geneva, Switzerland. Consensus statement (long version). J Hepatol. 2003;39 Suppl 1:S3–25.PubMedGoogle Scholar
  10. 10.
    Perz JF, Armstrong GL, Farrington LA, et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol. 2006;45(4):529–38.PubMedGoogle Scholar
  11. 11.
    Tabor E. Hepatocellular carcinoma: global epidemiology. Dig Liver Dis. 2001;33(2):115–7.PubMedGoogle Scholar
  12. 12.
    Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–128.PubMedGoogle Scholar
  13. 13.
    Ott JJ, Ullrich A, Mascarenhas M, et al. Global cancer incidence and mortality caused by behavior and infection. J Public Health (Oxf). 2011;33(2):223–33.Google Scholar
  14. 14.
    United Nations, Department of Economic and Social Affairs, Population Division. World population prospects: the 2012 revision; 2013.Google Scholar
  15. 15.
    McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis. 2005;25 Suppl 1:3–8.PubMedGoogle Scholar
  16. 16.
    Chang MH. Natural history of hepatitis B virus infection in children. J Gastroenterol Hepatol. 2000;15(Suppl):E16–9.PubMedGoogle Scholar
  17. 17.
    McMahon BJ, Alward WL, Hall DB, et al. Acute hepatitis B virus infection: relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis. 1985;151(4):599–603.PubMedGoogle Scholar
  18. 18.
    Ott JJ, Stevens GA, Groeger J, et al. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30(12):2212–9.PubMedGoogle Scholar
  19. 19.
    Lavanchy D. Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11(2):97–107.PubMedGoogle Scholar
  20. 20.
    Toukan AU, Sharaiha ZK, Abu-el-Rub OA, et al. The epidemiology of hepatitis B virus among family members in the Middle East. Am J Epidemiol. 1990;132(2):220–32.PubMedGoogle Scholar
  21. 21.
    Kew MC. Epidemiology of hepatocellular carcinoma in sub-Saharan Africa. Ann Hepatol. 2013;12(2):173–82.PubMedGoogle Scholar
  22. 22.
    Specialist Panel on Chronic Hepatitis B in the Middle East. A review of chronic hepatitis B epidemiology and management issues in selected countries in the Middle East. J Viral Hepat. 2012;19(1):9–22.Google Scholar
  23. 23.
    Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedGoogle Scholar
  24. 24.
    Margolis HS, Alter MJ, Hadler SC. Hepatitis B: evolving epidemiology and implications for control. Semin Liver Dis. 1991;11(2):84–92.PubMedGoogle Scholar
  25. 25.
    World Health Organization. The World Health report. Geneva: World Health Organization; 1997.Google Scholar
  26. 26.
    Shepard CW, Simard EP, Finelli L, et al. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev. 2006;28(1):112–25.PubMedGoogle Scholar
  27. 27.
    Alter MJ. Epidemiology and prevention of hepatitis B. Semin Liver Dis. 2003;23(1):39–46.PubMedGoogle Scholar
  28. 28.
    Childhood diseases in Africa. WHO, Global Programme for Vaccines and Immunization (GPV), Scientific Advisory Group of Experts (SAGE); 1996.Google Scholar
  29. 29.
    Toukan A. Strategy for the control of hepatitis B virus infection in the Middle East and North Africa The Middle East Regional Study Group. Vaccine. 1990;8(Suppl):S117–21. discussion S134–8.PubMedGoogle Scholar
  30. 30.
    Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000—summary of a workshop. Gastroenterology. 2001;120(7):1828–53.PubMedGoogle Scholar
  31. 31.
    McGlynn KA, Tsao L, Hsing AW, et al. International trends and patterns of primary liver cancer. Int J Cancer. 2001;94(2):290–6.PubMedGoogle Scholar
  32. 32.
    Lemon SM, Layden TJ, Seeff L, et al. The 20th United States-Japan Joint Hepatitis Panel Meeting. Hepatology. 2000;31(3):800–6.PubMedGoogle Scholar
  33. 33.
    Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedGoogle Scholar
  34. 34.
    Jilg W, Norder H, Kane M, et al. Reduced prevalence of HBsAg variants following a successful immunization program in China. J Virol. 2014;88(8):4605–6.PubMedCentralPubMedGoogle Scholar
  35. 35.
    Kane A, Lloyd J, Zaffran M, et al. Transmission of hepatitis B, hepatitis C and human immunodeficiency viruses through unsafe injections in the developing world: model-based regional estimates. Bull World Health Organization. 1999;77(10):801–7.Google Scholar
  36. 36.
    Kane M. Epidemiology of hepatitis B infection in North America. Vaccine. 1995;13 Suppl 1:S16–7.PubMedGoogle Scholar
  37. 37.
    Goldstein ST, Zhou F, Hadler SC, et al. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol. 2005;34(6):1329–39.PubMedGoogle Scholar
  38. 38.
    Lee WM. Hepatitis B virus infection. N Engl J Med. 1997;337(24):1733–45.PubMedGoogle Scholar
  39. 39.
    Hepatitis B immunization. WHO position paper. Wkly Epidemiol Rec. 2009;84:405–20.Google Scholar
  40. 40.
    WHO, UNICEF, World Bank. State of the world’s vaccines and immunization. Geneva: World Health Organization; 2009.Google Scholar
  41. 41.
    Goodnough LT. Risks of blood transfusion. Crit Care Med. 2003;31(12 Suppl):S678–86.PubMedGoogle Scholar
  42. 42.
    Schreiber GB, Busch MP, Kleinman SH, et al. The risk of transfusion-transmitted viral infections. N Engl J Med. 1996;334(26):1685–90.PubMedGoogle Scholar
  43. 43.
    WHO. Annual Meeting of the Safe Injection Global Network (SIGN); 2010. November 2010, United Arab Emirates. http://www.who.int/injection_safety/sign/meetings/en/ (accessed 12.08.2015)
  44. 44.
    Pruss-Ustun A, Rapiti E, Hutin Y. Estimation of the global burden of disease attributable to contaminated sharps injuries among health-care workers. Am J Ind Med. 2005;48(6):482–90.PubMedGoogle Scholar
  45. 45.
    World Health Organization (WHO). Hepatitis B position statement. Wkly Epidemiol Rec. 2009;84:405–20.Google Scholar
  46. 46.
    Medley GF, Lindop NA, Edmunds WJ, et al. Hepatitis-B virus endemicity: heterogeneity, catastrophic dynamics and control. Nat Med. 2001;7(5):619–24.PubMedGoogle Scholar
  47. 47.
    Wasley A, Grytdal S, Gallagher K, et al. Surveillance for acute viral hepatitis—United States, 2006. MMWR Surveill Summ. 2008;57(2):1–24.PubMedGoogle Scholar
  48. 48.
    Lavanchy D. Worldwide epidemiology of HBV infection, disease burden, and vaccine prevention. J Clin Virol. 2005;34 Suppl 1:S1–3.PubMedGoogle Scholar
  49. 49.
    Weinbaum CM, Williams I, Mast EE, et al. Recommendations for identification and public health management of persons with chronic hepatitis B virus infection. MMWR Recomm Rep. 2008;57(Rr-8):1–20.PubMedGoogle Scholar
  50. 50.
    Zanetti AR, Van Damme P, Shouval D. The global impact of vaccination against hepatitis B: a historical overview. Vaccine. 2008;26(49):6266–73.PubMedGoogle Scholar
  51. 51.
    WHO. Global policy report on the prevention and control of viral hepatitis in WHO Member States. Geneva: WHO; 2013.Google Scholar
  52. 52.
    Hwang SJ, Tong MJ, Lai PP, et al. Evaluation of hepatitis B and C viral markers: clinical significance in Asian and Caucasian patients with hepatocellular carcinoma in the United States of America. J Gastroenterol Hepatol. 1996;11(10):949–54.PubMedGoogle Scholar
  53. 53.
    Cotler SJ, Dhamija MK, Siqueira F, et al. Hepatitis B seroprevalence and disease characteristics in an urban Chinatown community. Clin Gastroenterol Hepatol. 2009;7(7):776–80.PubMedGoogle Scholar
  54. 54.
    Pon EW, Ren H, Margolis H, et al. Hepatitis B virus infection in Honolulu students. Pediatrics. 1993;92(4):574–8.PubMedGoogle Scholar
  55. 55.
    Villeneuve JP, Desrochers M, Infante-Rivard C, et al. A long-term follow-up study of asymptomatic hepatitis B surface antigen-positive carriers in Montreal. Gastroenterology. 1994;106(4):1000–5.PubMedGoogle Scholar
  56. 56.
    McMahon BJ, Lanier AP, Wainwright RB. Hepatitis B and hepatocellular carcinoma in Eskimo/Inuit population. Int J Circumpolar Health. 1998;57 Suppl 1:414–9.PubMedGoogle Scholar
  57. 57.
    Wong WW, Woo G, Heathcote EJ, et al. Disease burden of chronic hepatitis B among immigrants in Canada. Can J Gastroenterol. 2013;27(3):137–47.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Schmunis GA, Zicker F, Cruz JR, et al. Safety of blood supply for infectious diseases in Latin American countries, 1994–1997. Am J Trop Med Hyg. 2001;65(6):924–30.PubMedGoogle Scholar
  59. 59.
    Leon P, Venegas E, Bengoechea L, et al. Prevalencia de las infecciones por virus de las hepatitis B, C, D y E en Bolivia. Rev Panam Salud Publica. 1999;5(3):144–51.PubMedGoogle Scholar
  60. 60.
    Liao SS, Li RC, Li H, et al. Long-term efficacy of plasma-derived hepatitis B vaccine: a 15-year follow-up study among Chinese children. Vaccine. 1999;17(20–21):2661–6.PubMedGoogle Scholar
  61. 61.
    Tanaka H, Imai Y, Hiramatsu N, et al. Declining incidence of hepatocellular carcinoma in Osaka, Japan, from 1990 to 2003. Ann Intern Med. 2008;148(11):820–6.PubMedGoogle Scholar
  62. 62.
    Ng KP, Saw TL, Baki A, et al. Impact of the Expanded Program of Immunization against hepatitis B infection in school children in Malaysia. Med Microbiol Immunol. 2005;194(3):163–8.PubMedGoogle Scholar
  63. 63.
    Wait S, Chen DS. Towards the eradication of hepatitis B in Taiwan. Kaohsiung J Med Sci. 2012;28(1):1–9.PubMedGoogle Scholar
  64. 64.
    Chien YC, Jan CF, Kuo HS, et al. Nationwide hepatitis B vaccination program in Taiwan: effectiveness in the 20 years after it was launched. Epidemiol Rev. 2006;28:126–35.PubMedGoogle Scholar
  65. 65.
    Singh H, Aggarwal R, Singh RL, et al. Frequency of infection by hepatitis B virus and its surface mutants in a northern Indian population. Indian J Gastroenterol. 2003;22(4):132–7.PubMedGoogle Scholar
  66. 66.
    Kurien T, Thyagarajan SP, Jeyaseelan L, et al. Community prevalence of hepatitis B infection and modes of transmission in Tamil Nadu, India. Indian J Med Res. 2005;121(5):670–5.PubMedGoogle Scholar
  67. 67.
    Chowdhury A, Santra A, Chaudhuri S, et al. Prevalence of hepatitis B infection in the general population: a rural community based study. Trop Gastroenterol. 1999;20(2):75–7.PubMedGoogle Scholar
  68. 68.
    Centers for Disease Control and Prevention (CDC). Progress in hepatitis B prevention through universal infant vaccination—China, 1997–2006. MMWR Morb Mortal Wkly Rep. 2007;56(18):441–5.Google Scholar
  69. 69.
    Liang X, Bi S, Yang W, et al. Epidemiological serosurvey of hepatitis B in China—declining HBV prevalence due to hepatitis B vaccination. Vaccine. 2009;27(47):6550–7.PubMedGoogle Scholar
  70. 70.
    Kane MA, Hadler SC, Lee L, et al. The inception, achievements, and implications of the China GAVI Alliance Project on Hepatitis B Immunization. Vaccine. 2013;31 Suppl 9:J15–20.PubMedGoogle Scholar
  71. 71.
    MacLachlan JH, Allard N, Towell V, et al. The burden of chronic hepatitis B virus infection in Australia, 2011. Aust N Z J Public Health. 2013;37(5):416–22.PubMedGoogle Scholar
  72. 72.
    Gust ID. Epidemiology of hepatitis B infection in the Western Pacific and South East Asia. Gut. 1996;38 Suppl 2:S18–23.PubMedCentralPubMedGoogle Scholar
  73. 73.
    MacLachlan J, Cowie B. Chronic hepatitis B—what’s new? Aust Fam Physician. 2013;42(7):448–51.PubMedGoogle Scholar
  74. 74.
    Graham S, Guy RJ, Cowie B, et al. Chronic hepatitis B prevalence among Aboriginal and Torres Strait Islander Australians since universal vaccination: a systematic review and meta-analysis. BMC Infect Dis. 2013;13:403.PubMedCentralPubMedGoogle Scholar
  75. 75.
    Howell J, Van Gemert C, Lemoine M, et al. An overview of hepatitis B prevalence, prevention, and management in the Pacific Islands and Territories. J Gastroenterol Hepatol. 2014;29(11):1854–66.PubMedGoogle Scholar
  76. 76.
    Hahne SJ, Veldhuijzen IK, Wiessing L, et al. Infection with hepatitis B and C virus in Europe: a systematic review of prevalence and cost-effectiveness of screening. BMC Infect Dis. 2013;13:181.PubMedCentralPubMedGoogle Scholar
  77. 77.
    Rantala M, van de Laar MJ. Surveillance and epidemiology of hepatitis B and C in Europe—a review. Euro Surveill. 2008;13(21):1–8.Google Scholar
  78. 78.
    Andre F. Hepatitis B epidemiology in Asia, the Middle East and Africa. Vaccine. 2000;18 Suppl 1:S20–2.PubMedGoogle Scholar
  79. 79.
    Alavian SM, Tabatabaei SV, Ghadimi T, et al. Seroprevalence of Hepatitis B virus infection and its risk factors in the west of Iran: a population-based study. Int J Prev Med. 2012;3(11):770–5.PubMedCentralPubMedGoogle Scholar
  80. 80.
    Zali MR, Mohammad K, Noorbala AA, et al. Rate of hepatitis B seropositivity following mass vaccination in the Islamic Republic of Iran. East Mediterr Health J. 2005;11(1–2):62–7.PubMedGoogle Scholar
  81. 81.
    Alavian SM, Hajarizadeh B, Ahmadzad-Asl M, et al. Hepatitis B virus infection in Iran: a systematic review. Hepat Mon. 2008;8(4):281–94.Google Scholar
  82. 82.
    VHPB (Viral Hepatitis Prevention Board). Prevention and control of viral hepatitis in migrants and refugees. VHPB-meeting. Viral Hepat. 2000;8(2):1–7.Google Scholar
  83. 83.
    Ott JJ, Paltiel AM, Winkler V, et al. Chronic disease mortality associated with infectious agents: a comparative cohort study of migrants from the Former Soviet Union in Israel and Germany. BMC Public Health. 2008;8:110.PubMedCentralPubMedGoogle Scholar
  84. 84.
    Friede A, Harris JR, Kobayashi JM, et al. Transmission of hepatitis B virus from adopted Asian children to their American families. Am J Public Health. 1988;78(1):26–9.PubMedCentralPubMedGoogle Scholar
  85. 85.
    Nordenfelt E, Dahlquist E. HBsAg positive adopted children as a cause of intrafamilial spread of hepatitis B. Scand J Infect Dis. 1978;10(3):161–3.PubMedGoogle Scholar
  86. 86.
    Lange WR, Warnock-Eckhart E. Selected infectious disease risks in international adoptees. Pediatr Infect Dis J. 1987;6(5):447–50.PubMedGoogle Scholar
  87. 87.
    Chu JJ, Wormann T, Popp J, et al. Changing epidemiology of hepatitis B and migration—a comparison of six Northern and North-Western European countries. Eur J Public Health. 2013;23(4):642–7.PubMedGoogle Scholar
  88. 88.
    Nelson PK, Mathers BM, Cowie B, et al. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011;378(9791):571–83.PubMedCentralPubMedGoogle Scholar
  89. 89.
    World Health Organization. Guidance on prevention of viral hepatitis B and C among people who inject drugs. Geneva: World Health Organization; 2012.Google Scholar
  90. 90.
    Alter MJ, Margolis HS. The emergence of hepatitis B as a sexually transmitted disease. Med Clin North Am. 1990;74(6):1529–41.PubMedGoogle Scholar
  91. 91.
    Corona R, Caprilli F, Giglio A, et al. Risk factors for hepatitis B virus infection among heterosexuals attending a sexually transmitted diseases clinic in Italy: role of genital ulcerative diseases. J Med Virol. 1996;48(3):262–6.PubMedGoogle Scholar
  92. 92.
    Gan CY, Yap SF, Ngeow YF, et al. Hepatitis B infection among Chinese STD patients in Kuala Lumpur, Malaysia. Sex Transm Dis. 1991;18(2):84–8.PubMedGoogle Scholar
  93. 93.
    Struve J, Giesecke J, Lindh G, et al. Heterosexual contact as a major route for transmission of acute hepatitis B among adults. J Infect. 1990;20(2):111–21.PubMedGoogle Scholar
  94. 94.
    Germinario C, Luigi Lopalco P, Chicanna M, et al. From hepatitis B to hepatitis A and B prevention: the Puglia (Italy) experience. Vaccine. 2000;18(28):3326.PubMedGoogle Scholar
  95. 95.
    Spada E, Mele A, Ciccozzi M, et al. Changing epidemiology of parenterally transmitted viral hepatitis: results from the hepatitis surveillance system in Italy. Dig Liver Dis. 2001;33(9):778–84.PubMedGoogle Scholar
  96. 96.
    Mele A, Spada E, Sagliocca L, et al. Risk of parenterally transmitted hepatitis following exposure to surgery or other invasive procedures: results from the hepatitis surveillance system in Italy. J Hepatol. 2001;35(2):284–9.PubMedGoogle Scholar
  97. 97.
    Goldstein ST, Alter MJ, Williams IT, et al. Incidence and risk factors for acute hepatitis B in the United States, 1982–1998: implications for vaccination programs. J Infect Dis. 2002;185(6):713–9.PubMedGoogle Scholar
  98. 98.
    van Steenbergen JE, Niesters HG, Op de Coul EL, et al. Molecular epidemiology of hepatitis B virus in Amsterdam 1992–1997. J Med Virol. 2002;66(2):159–65.PubMedGoogle Scholar
  99. 99.
    Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006;44(1 Suppl):S6–9.PubMedGoogle Scholar
  100. 100.
    Sulkowski MS. Viral hepatitis and HIV coinfection. J Hepat. 2008;48(2):353–67.Google Scholar
  101. 101.
    Hauri AM, Armstrong GL, Hutin YJ. The global burden of disease attributable to contaminated injections given in health care settings. Int J STD AIDS. 2004;15(1):7–16.PubMedGoogle Scholar
  102. 102.
    Prüss-Ustün A, Rapiti E, Hutin Y. Sharps injuries: global burden of disease from sharps injuries to health-care workers, in WHO Environmental Burden of Disease Series. Geneva: World Health Organization; 2003.Google Scholar
  103. 103.
    FitzSimons D, Francois G, De Carli G, et al. Hepatitis B virus, hepatitis C virus and other blood-borne infections in healthcare workers: guidelines for prevention and management in industrialised countries. Occup Environ Med. 2008;65(7):446–51.PubMedGoogle Scholar
  104. 104.
    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(3):694–702.PubMedGoogle Scholar
  105. 105.
    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(7):1750–8.PubMedGoogle Scholar
  106. 106.
    Hollinger FB, Sood G. Occult hepatitis B virus infection: a covert operation. J Viral Hepat. 2010;17(1):1–15.PubMedGoogle Scholar
  107. 107.
    Huang X, Hollinger FB. Occult hepatitis B virus infection and hepatocellular carcinoma: a systematic review. J Viral Hepat. 2014;21(3):153–62.PubMedGoogle Scholar
  108. 108.
    Hollinger FB. Hepatitis B virus infection and transfusion medicine: science and the occult. Transfusion. 2008;48(5):1001–26.PubMedGoogle Scholar
  109. 109.
    Allain JP. Occult hepatitis B virus infection: implications in transfusion. Vox Sang. 2004;86(2):83–91.PubMedGoogle Scholar
  110. 110.
    WHO. WHO vaccine-preventable diseases monitoring system, 2010 global summary, WHO/IVB/2010. Geneva: WHO; 2010.Google Scholar
  111. 111.
    Chang MH, You SL, Chen CJ, et al. Decreased incidence of hepatocellular carcinoma in hepatitis B vaccinees: a 20-year follow-up study. J Natl Cancer Inst. 2009;101(19):1348–55.PubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.DengesSwitzerland
  2. 2.Mercer IslandUSA

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