Global Epidemiology of Acute Viral Hepatitis A–E

  • Hubert E. BlumEmail author


Worldwide, viral hepatitides are caused by five well-characterized hepatotropic viruses: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus (HDV), and hepatitis E virus (HEV). Their epidemiology as well as their pathogenesis have been studied in great detail. Further, the structure and genetic organization of their DNA or RNA genome including the viral life cycle have been elucidated. These discoveries have been successfully translated into important clinical applications, such as the specific diagnosis, therapy, and prevention of the associated liver diseases, including acute or fulminant hepatitis, as well as the long-term sequelae of chronic hepatitis, including liver cirrhosis and hepatocellular carcinoma (HCC).

The prevalence of viral hepatitis A–E shows distinct geographic differences. The global burden of these infections (prevalence, incidence, cause-specific death, disability-adjusted life years, and years of life lost) has recently been analyzed in seminal studies. During the coming decade(s) we expect to further improve our ability to prevent and to effectively treat viral hepatitis A–E, resulting in the control or even elimination of these global infections and of their associated morbidities and mortalities.


Viral hepatitis Hepatitis A virus Hepatitis B virus Hepatitis C virus Hepatitis D virus Hepatitis E virus 


  1. 1.
    Feinstone SM, Kapikian AZ, Purceli RH. Hepatitis A: detection by immune electron microscopy of a viruslike antigen associated with acute illness. Science. 1973;182:1026–8.CrossRefGoogle Scholar
  2. 2.
    Martin A, Lemon SM. Hepatitis A virus: from discovery to vaccines. Hepatology. 2006;43:S164–72.CrossRefGoogle Scholar
  3. 3.
    Blumberg BS, Alter HJ, Visnich S. A “New” Antigen in Leukemia Sera. JAMA. 1965;191:541–6.CrossRefGoogle Scholar
  4. 4.
    Blumberg BS, Gerstley BJ, Hungerford DA, London WT, Sutnick AI. A serum antigen (Australia antigen) in Down’s syndrome, leukemia, and hepatitis. Ann Intern Med. 1967;66:924–31.CrossRefGoogle Scholar
  5. 5.
    Prince AM. An antigen detected in the blood during the incubation period of serum hepatitis. Proc Natl Acad Sci U S A. 1968;60:814–21.CrossRefGoogle Scholar
  6. 6.
    Prince AM. Relation of Australia and SH antigens. Lancet. 1968;2:462–3.CrossRefGoogle Scholar
  7. 7.
    Prince AM, Hargrove RL, Szmuness W, Cherubin CE, Fontana VJ, Jeffries GH. Immunologic distinction between infectious and serum hepatitis. N Engl J Med. 1970;282:987–91.CrossRefGoogle Scholar
  8. 8.
    Krugman S, Giles JP. Viral hepatitis. New light on an old disease. JAMA. 1970;212:1019–29.CrossRefGoogle Scholar
  9. 9.
    Bukh J, Purcell RH, Miller RH. Sequence analysis of the core gene of 14 hepatitis C virus genotypes. Proc Natl Acad Sci U S A. 1994;91:8239–43.CrossRefGoogle Scholar
  10. 10.
    Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359–62.CrossRefGoogle Scholar
  11. 11.
    Kuo G, Choo QL, Alter HJ, Gitnick GL, Redeker AG, Purcell RH, Miyamura T, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science. 1989;244:362–4.CrossRefGoogle Scholar
  12. 12.
    Alter HJ, Purcell RH, Shih JW, Melpolder JC, Houghton M, Choo QL, Kuo G. Detection of antibody to hepatitis C virus in prospectively followed transfusion recipients with acute and chronic non-A, non-B hepatitis. N Engl J Med. 1989;321:1494–500.CrossRefGoogle Scholar
  13. 13.
    Ghany MG, Strader DB, Thomas DL, Seeff LB, American Association for the Study of Liver D. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–74.CrossRefGoogle Scholar
  14. 14.
    Centers for Disease C, Prevention. Testing for HCV infection: an update of guidance for clinicians and laboratorians. MMWR Morb Mortal Wkly Rep. 2013;62:362–5.Google Scholar
  15. 15.
    Webster DP, Klenerman P, Dusheiko GM. Hepatitis C. Lancet. 2015;385:1124–35.CrossRefGoogle Scholar
  16. 16.
    Rizzetto M, Canese MG, Arico S, Crivelli O, Trepo C, Bonino F, Verme G. 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;18:997–1003.CrossRefGoogle Scholar
  17. 17.
    Rizzetto M, Hoyer B, Canese MG, Shih JW, Purcell RH, Gerin JL. Delta agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees. Proc Natl Acad Sci U S A. 1980;77:6124–8.CrossRefGoogle Scholar
  18. 18.
    Gupta DN, Smetana HF. The histopathology of viral hepatitis as seen in the Delhi epidemic (1955–56). Indian J Med Res. 1957;45:101–13.PubMedGoogle Scholar
  19. 19.
    Balayan MS, Andjaparidze AG, Savinskaya SS, Ketiladze ES, Braginsky DM, Savinov AP, Poleschuk VF. Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology. 1983;20:23–31.CrossRefGoogle Scholar
  20. 20.
    Kane MA, Bradley DW, Shrestha SM, Maynard JE, Cook EH, Mishra RP, Joshi DD. Epidemic non-A, non-B hepatitis in Nepal. Recovery of a possible etiologic agent and transmission studies in marmosets. JAMA. 1984;252:3140–5.CrossRefGoogle Scholar
  21. 21.
    Krawczynski K, Bradley DW. Enterically transmitted non-A, non-B hepatitis: identification of virus-associated antigen in experimentally infected cynomolgus macaques. J Infect Dis. 1989;159:1042–9.CrossRefGoogle Scholar
  22. 22.
    Hoofnagle JH, Nelson KE, Purcell RH. Hepatitis E. N Engl J Med. 2012;367:1237–44.CrossRefGoogle Scholar
  23. 23.
    Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J, Dalton HR. Hepatitis E. Lancet. 2012;379:2477–88.CrossRefGoogle Scholar
  24. 24.
    Jacobsen KH, Wiersma ST. Hepatitis A virus seroprevalence by age and world region, 1990 and 2005. Vaccine. 2010;28:6653–7.CrossRefGoogle Scholar
  25. 25.
    Wasley A, Fiore A, Bell BP. Hepatitis A in the era of vaccination. Epidemiol Rev. 2006;28:101–11.CrossRefGoogle Scholar
  26. 26.
    Wasley A, Samandari T, Bell BP. Incidence of hepatitis A in the United States in the era of vaccination. JAMA. 2005;294:194–201.CrossRefGoogle Scholar
  27. 27.
    Advisory Committee on Immunization P, Fiore AE, Wasley A, Bell BP. Prevention of hepatitis A through active or passive immunization: recommendations of the advisory committee on immunization practices (ACIP). MMWR Recomm Rep. 2006;55:1–23.Google Scholar
  28. 28.
    Wasley A, Grytdal S, Gallagher K. Centers for disease C, prevention. Surveillance for acute viral hepatitis—United States, 2006. MMWR Surveill Summ. 2008;57:1–24.PubMedGoogle Scholar
  29. 29.
    Daniels D, Grytdal S, Wasley A, Centers for Disease C, Prevention. Surveillance for acute viral hepatitis—United States, 2007. MMWR Surveill Summ. 2009;58:1–27.PubMedGoogle Scholar
  30. 30.
    Klevens RM, Miller JT, Iqbal K, Thomas A, Rizzo EM, Hanson H, Sweet K, et al. The evolving epidemiology of hepatitis a in the United States: incidence and molecular epidemiology from population-based surveillance, 2005–2007. Arch Intern Med. 2010;170:1811–8.CrossRefGoogle Scholar
  31. 31.
    Ganem D, Prince AM. Hepatitis B virus infection—natural history and clinical consequences. N Engl J Med. 2004;350:1118–29.CrossRefGoogle Scholar
  32. 32.
    Ott JJ, Stevens GA, Groeger J, Wiersma ST. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine. 2012;30:2212–9.CrossRefGoogle Scholar
  33. 33.
    Wasley A, Kruszon-Moran D, Kuhnert W, Simard EP, Finelli L, McQuillan G, Bell B. The prevalence of hepatitis B virus infection in the United States in the era of vaccination. J Infect Dis. 2010;202:192–201.CrossRefGoogle Scholar
  34. 34.
    Ly KN, Xing J, Klevens RM, Jiles RB, Ward JW, Holmberg SD. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012;156:271–8.CrossRefGoogle Scholar
  35. 35.
    Mast EE, Weinbaum CM, Fiore AE, Alter MJ, Bell BP, Finelli L, Rodewald LE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the advisory committee on immunization practices (ACIP) part II: immunization of adults. MMWR Recomm Rep. 2006;55:1–33; quiz CE31–34.PubMedGoogle Scholar
  36. 36.
    Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013;57:1333–42.CrossRefGoogle Scholar
  37. 37.
    Rizzetto M, Ponzetto A, Forzani I. Hepatitis delta virus as a global health problem. Vaccine. 1990;8(Suppl):S10–4; discussion S21–13.CrossRefGoogle Scholar
  38. 38.
    Hughes SA, Wedemeyer H, Harrison PM. Hepatitis delta virus. Lancet. 2011;378:73–85.CrossRefGoogle Scholar
  39. 39.
    Gaeta GB, Stroffolini T, Chiaramonte M, Ascione T, Stornaiuolo G, Lobello S, Sagnelli E, et al. Chronic hepatitis D: a vanishing disease? An Italian multicenter study. Hepatology. 2000;32:824–7.CrossRefGoogle Scholar
  40. 40.
    Cross TJ, Rizzi P, Horner M, Jolly A, Hussain MJ, Smith HM, Vergani D, et al. The increasing prevalence of hepatitis delta virus (HDV) infection in South London. J Med Virol. 2008;80:277–82.CrossRefGoogle Scholar
  41. 41.
    Wedemeyer H, Heidrich B, Manns MP. Hepatitis D virus infection—not a vanishing disease in Europe! Hepatology. 2007;45:1331–2; author reply 1332–1333CrossRefGoogle Scholar
  42. 42.
    Borresen ML, Olsen OR, Ladefoged K, McMahon BJ, Hjuler T, Panum I, Simonetti J, et al. Hepatitis D outbreak among children in a hepatitis B hyper-endemic settlement in Greenland. J Viral Hepat. 2010;17:162–70.CrossRefGoogle Scholar
  43. 43.
    Tsatsralt-Od B, Takahashi M, Endo K, Buyankhuu O, Baatarkhuu O, Nishizawa T, Okamoto H. Infection with hepatitis A, B, C, and delta viruses among patients with acute hepatitis in Mongolia. J Med Virol. 2006;78:542–50.CrossRefGoogle Scholar
  44. 44.
    Emerson SU, Purcell RH. Running like water—the omnipresence of hepatitis E. N Engl J Med. 2004;351:2367–8.CrossRefGoogle Scholar
  45. 45.
    Stramer SL, Moritz ED, Foster GA, Ong E, Linnen JM, Hogema BM, Mak M, et al. Hepatitis E virus: seroprevalence and frequency of viral RNA detection among US blood donors. Transfusion. 2016;56:481–8.CrossRefGoogle Scholar
  46. 46.
    Kuniholm MH, Purcell RH, McQuillan GM, Engle RE, Wasley A, Nelson KE. Epidemiology of hepatitis E virus in the United States: results from the third national health and nutrition examination survey, 1988–1994. J Infect Dis. 2009;200:48–56.CrossRefGoogle Scholar
  47. 47.
    Teshale EH, Denniston MM, Drobeniuc J, Kamili S, Teo CG, Holmberg SD. Decline in hepatitis E virus antibody prevalence in the United States from 1988–1994 to 2009–2010. J Infect Dis. 2015;211:366–73.CrossRefGoogle Scholar
  48. 48.
    Shrestha MP, Scott RM, Joshi DM, Mammen MP Jr, Thapa GB, Thapa N, Myint KS, et al. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med. 2007;356:895–903.CrossRefGoogle Scholar
  49. 49.
    Zhu FC, Zhang J, Zhang XF, Zhou C, Wang ZZ, Huang SJ, Wang H, et al. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010;376:895–902.CrossRefGoogle Scholar
  50. 50.
    Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HL, Chen CJ, Chen DS, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int. 2016;10:1–98.CrossRefGoogle Scholar
  51. 51.
    Peron JM, Abravanel F, Guillaume M, Gerolami R, Nana J, Anty R, Pariente A, et al. Treatment of autochthonous acute hepatitis E with short-term ribavirin: a multicenter retrospective study. Liver Int. 2016;36:328–33.CrossRefGoogle Scholar
  52. 52.
    Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, 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;380:2095–128.CrossRefGoogle Scholar
  53. 53.
    Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380:2197–223.CrossRefGoogle Scholar
  54. 54.
    Global Burden of Disease Study C. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the global burden of disease study 2013. Lancet:2015.Google Scholar
  55. 55.
    Collaborators GBDCoD. Global, regional, and national age-sex specific mortality for 264 causes of death, 1980–2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2017;390:1151–210.CrossRefGoogle Scholar
  56. 56.
    DALYs GBD, Collaborators H. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet. 2017;390:1260–344.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.University Hospital FreiburgFreiburg im BreisgauGermany

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