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Transmission routes and risk factors for autochthonous hepatitis E virus infection in Europe: a systematic review

  • H. C. LEWIS (a1) (a2), O. WICHMANN (a3) and E. DUIZER (a4)

Increasing numbers of non-travel-associated hepatitis E virus (HEV) infections have been reported in Europe in recent years. Our objective was to review the evidence on risk factors and transmission routes of autochthonous HEV infection and hepatitis E in Europe in order to develop recommendations for future research, prevention and control. A systematic literature review was performed to identify all primary reports and studies published during 1998–2008 on hepatitis E in humans and animals in Europe by searching Pubmed, reference lists of major articles and international conference proceedings. Each of the 106 included studies was categorized into one of three evidence levels (EL) based on study design and diagnostic methodology. The evidence was generally weak (73 were assigned to EL1, two to both EL1 and EL2, and 30 to EL2), further compounded by the use of poorly validated serological assays in some studies. Only one case-control study was assigned to EL3. Persons with autochthonous hepatitis E infection were on average older than the general population and predominantly male. There was no evidence for one main transmission route of HEV infection or risk factor for hepatitis E. However, zoonotic transmission seemed likely and person-to-person transmission too inefficient to cause clinical disease. Multiple routes of transmission probably exist and should be further investigated through analytical studies and reliable diagnostic kits. Based on current evidence that points to zoonotic transmission from pigs, thorough cooking of all porcine products, prevention of cross-contamination in the kitchen and improved education for occupationally exposed people (e.g. pig farmers, veterinarians and sewage workers) may help prevent HEV infection. Although evidence for parenteral transmission is limited, it is recommended that a risk assessment is undertaken.

Corresponding author
*Author for correspondence: Miss H. C. Lewis, Epidemiologist, World Health Organization Lao PDR Country Office, P.O. Box 343, Vientiane, Lao PDR. (Email:
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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

1. AB Labrique , Hepatitis E: an emerging infectious disease. Epidemiologic Reviews 1999; 21: 162179.

2. H Okamoto , M Takahashi , T Nishizawa . Features of hepatitis E virus infection in Japan. Internal Medicine 2003; 42: 10651071.

3. A Boutrouille , Prevalence of anti-hepatitis E virus antibodies in French blood donors. Journal of Clinical Microbiology 2007; 45: 20092010.

4. M Buti , Community-based seroepidemiological survey of hepatitis E virus infection in Catalonia, Spain. Clinical and Vaccine Immunology 2006; 13: 13281332.

5. PB Christensen , Time trend of the prevalence of hepatitis E antibodies among farmers and blood donors: a potential zoonosis in Denmark. Clinical Infectious Diseases 2008; 47: 10261031.

6. M Herremans , Swine-like hepatitis E viruses are a cause of unexplained hepatitis in the Netherlands. Journal of Viral Hepatitis 2007; 14: 140146.

7. XJ Meng , Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries. Journal of Clinical Microbiology 2002; 40: 117122.

8. B Olsen , Unexpected high prevalence of IgG-antibodies to hepatitis E virus in Swedish pig farmers and controls. Scandinavian Journal of Infectious Diseases 2006; 38: 5558.

9. H Toyoda , Prevalence of hepatitis E virus IgG antibody in Japanese patients with hemophilia. Intervirology 2008; 51: 2125.

11. CG Teo . Hepatitis E indigenous to economically developed countries: to what extent a zoonosis? Current Opinion in Infectious Diseases 2006; 19: 460466.

12. CG Teo . The two clinico-epidemiological forms of hepatitis E. Journal of Viral Hepatitis 2007; 14: 295297.

13. MS Balayan , Brief report: experimental hepatitis E infection in domestic pigs. Journal of Medical Virology 1990; 32: 5859.

14. XJ Meng , A novel virus in swine is closely related to the human hepatitis E virus. Proceedings of the National Academy of Sciences USA 1997; 94: 98609865.

15. SK Ha , C Chae . Immunohistochemistry for the detection of swine hepatitis E virus in the liver. Journal of Viral Hepatitis 2004; 11: 263267.

16. TP Williams , Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model. Journal of Clinical Microbiology 2001; 39: 30403046.

20. RH Purcell , SU Emerson . Hepatitis E: an emerging awareness of an old disease. Journal of Hepatology 2008; 48: 494503.

21. M Herremans , Use of serological assays for diagnosis of hepatitis E virus genotype 1 and 3 infections in a setting of low endemicity. Clinical and Vaccine Immunology 2007; 14: 562568.

23. EE Mast , Evaluation of assays for antibody to hepatitis E virus by a serum panel. Hepatitis E Virus Antibody Serum Panel Evaluation Group. Hepatology 1998; 27: 857861.

28. R Gerolami , V Moal , P Colson . Chronic hepatitis E with cirrhosis in a kidney-transplant recipient. New England Journal of Medicine 2008; 358: 859860.

29. N Kamar , Hepatitis E virus and chronic hepatitis in organ-transplant recipients. New England Journal of Medicine 2008; 358: 811817.

30. H Mizuo , Possible risk factors for the transmission of hepatitis E virus and for the severe form of hepatitis E acquired locally in Hokkaido, Japan. Journal of Medical Virology 2005; 76: 341349.

31. HR Dalton , Autochthonous hepatitis E in Southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease. European Journal of Gastroenterology and Hepatology 2008; 20: 784790.

32. S Ijaz , Non-travel-associated hepatitis e in England and Wales: demographic, clinical, and molecular epidemiological characteristics. Journal of Infectious Diseases 2005; 192: 11661172.

38. HR Dalton , The role of hepatitis E virus testing in drug-induced liver injury. Alimentary Pharmacology & Therapeutics 2007; 26: 14291435.

39. AN De Silva , Unexpectedly high incidence of indigenous acute hepatitis E within South Hampshire: time for routine testing? Journal of Medical Virology 2008; 80: 283288.

40. A Haagsman , Seroepidemiology of hepatitis E virus in patients with non-A, non-B, non-C hepatitis in Hungary. Journal of Medical Virology 2007; 79: 927930.

43. S Palmer , D Brown , D Morgan . Early qualitative risk assessment of the emerging zoonotic potential of animal diseases. British Medical Journal 2005; 331: 12561260.

46. N Albinana-Gimenez , Distribution of human polyomaviruses, adenoviruses, and hepatitis E virus in the environment and in a drinking-water treatment plant. Environmental Science & Technology 2006; 40: 74167422.

47. P Clemente-Casares , Hepatitis E virus epidemiology in industrialized countries. Emerging Infectious Diseases 2003; 9: 448454.

49. HR Dalton , Locally acquired hepatitis E in chronic liver disease. Lancet 2007; 369: 1260.

50. HC Lewis , Hepatitis E in England and Wales. Emerging Infectious Diseases 2008; 14: 165167.

51. C Renou , A national survey of acute hepatitis E in France. Alimentary Pharmacology & Therapeutics 2008; 27: 10861093.

52. O Wichmann , Phylogenetic and case-control study on hepatitis E virus infection in Germany. Journal of Infectious Diseases 2008; 198: 17321741.

54. HR Dalton , Autochthonous hepatitis E in Southwest England: a comparison with hepatitis A. European Journal of Clinical Microbiology and Infectious Diseases 2008; 27: 579585.

56. PB Christensen , High prevalence of hepatitis E antibodies among Danish prisoners and drug users. Journal of Medical Virology 2002; 66: 4955.

62. M Banks , Evidence for the presence of hepatitis E virus in pigs in the United Kingdom. Veterinary Record 2004; 154: 223227.

63. I Di Bartolo , Widespread diffusion of genotype 3 hepatitis E virus among farming swine in Northern Italy. Veterinary Microbiology 2008; 132: 4755.

66. A Caprioli , Detection of hepatitis E virus in Italian pig herds. Veterinary Record 2007; 161: 422423.

67. HR Dalton , Autochthonous hepatitis E in southwest England. Journal of Viral Hepatitis 2007; 14: 304309.

69. JC Preiss , Autochthonous hepatitis E virus infection in Germany with sequence similarities to other European isolates. Infection 2006; 34: 173175.

70. G Reuter , Identification of a novel variant of human hepatitis E virus in Hungary. Journal of Clinical Virology 2006; 36: 100102.

72. M Banks , Human and porcine hepatitis E virus strains, United Kingdom. Emerging Infectious Diseases 2004; 10: 953955.

73. M Bouwknegt , Estimation of hepatitis E virus transmission among pigs due to contact-exposure. Veterinary Research 2008; 39: 40.

74. C McCreary , Excretion of hepatitis E virus by pigs of different ages and its presence in slurry stores in the United Kingdom. Veterinary Record 2008; 163: 261265.

76. S Pina , HEV identified in serum from humans with acute hepatitis and in sewage of animal origin in Spain. Journal of Hepatology 2000; 33: 826833.

77. P Colson , Hepatitis E associated with surgical training on pigs. Lancet 2007; 370: 935.

79. GL Lockwood , Hepatitis E autochthonous infection in chronic liver disease. European Journal of Gastroenterology and Hepatology 2008; 20: 800803.

81. JM Peron , Prolonged hepatitis E in an immunocompromised patient. Journal of Gastroenterology and Hepatology 2006; 21: 12231224.

83. SY Boomkens , PCR screening for candidate etiological agents of canine hepatitis. Veterinary Microbiology 2005; 108: 4955.

85. GJ Sadler , UK acquired hepatitis E – An emerging problem? Journal of Medical Virology 2006; 78: 473475.

87. P Colson , Severe thrombocytopenia associated with acute hepatitis E. Journal of Clinical Microbiology 2008; 46: 24502452.

90. R Moucari , Acute hepatitis E with severe jaundice: report of three cases. European Journal of Gastroenterology and Hepatology 2007; 19: 10121015.

91. WJ Hartmann , GG Frosner , D Eichenlaub . Transmission of hepatitis E in Germany. Infection 1998; 26: 409

95. E Boxall , Transfusion-transmitted hepatitis E in a ‘nonhyperendemic’ country. Transfusion Medicine 2006; 16: 7983.

97. ML Mateos , Hepatitis E virus: relevance in blood donors and risk groups. Vox Sanguinis 1999; 76: 7880.

99. M Nubling , F Hofmann , FW Tiller . Occupational risk for hepatitis A and hepatitis E among health care professionals? Infection 2002; 30: 9497.

101. M Rapicetta , Seroprevalence and anti-HEV persistence in the general population of the Republic of San Marino. Journal of Medical Virology 1999; 58: 4953.

102. AR Zanetti , Identification of a novel variant of hepatitis E virus in Italy. Journal of Medical Virology 1999; 57: 356360.

103. XJ Meng . Hepatitis E as a zoonotic disease. In: H Thomas , S Lemon , A Zuckerman , eds. Viral Hepatitis. Oxford: Blackwell Publishing, 2005, pp. 611623.

105. S Tei , Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet 2003; 362: 371373.

106. TC Li , Hepatitis E virus transmission from wild boar meat. Emerging Infectious Diseases 2005; 11: 19581960.

108. SU Emerson , VA Arankalle , RH Purcell . Thermal stability of hepatitis E virus. Journal of Infectious Diseases 2005; 192: 930933.

110. W Zhang , Hepatitis E virus infection among domestic animals in eastern China. Zoonoses and Public Health 2008; 55: 291298.

112. J Zhang , Randomized-controlled phase II clinical trial of a bacterially expressed recombinant hepatitis E vaccine. Vaccine 2009; 27: 18691874.

115. P Malcolm , The histology of acute autochthonous hepatitis E virus infection. Histopathology 2007; 51: 190194.

118. R McCrudden , Sporadic acute hepatitis E in the United Kingdom: an underdiagnosed phenomenon? Gut 2000; 46: 732733.

119. J Serratrice , Acute polyarthritis revealing hepatitis E. Clinical Rheumatology 2007; 26: 19731975.

120. JM Peron , Liver histology in patients with sporadic acute hepatitis E: a study of 11 patients from South-West France. Virchows Archiv 2007; 450: 405410.

121. JM Mansuy , Immunologically silent autochthonous acute hepatitis E virus infection in France. Journal of Clinical Microbiology 2004; 42: 912913.

122. A Grieco , Sporadic HEV hepatitis in Italy. Gut 2001; 48: 580

123. WB Melenhorst , Locally acquired hepatitis E in the Netherlands: associated with the consumption of raw pig meat? Scandinavian Journal of Infectious Diseases 2007; 39: 454456.

124. MA Widdowson , Cluster of cases of acute hepatitis associated with hepatitis E virus infection acquired in the Netherlands. Clinical Infectious Diseases 2003; 36: 2933.

125. JM Mansuy , Hepatitis E in the south west of France in individuals who have never visited an endemic area. Journal of Medical Virology 2004; 74: 419424.

126. GG Schlauder , Novel hepatitis E virus (HEV) isolates from Europe: evidence for additional genotypes of HEV. Journal of Medical Virology 1999; 57: 243251.

128. S Kaci , K Nockler , R Johne . Detection of hepatitis E virus in archived German wild boar serum samples. Veterinary Microbiology 2008; 128: 380385.

130. F Martelli , Detection of hepatitis E virus (HEV) in a demographic managed wild boar (Sus scrofa scrofa) population in Italy. Veterinary Microbiology 2008; 126: 7481.

131. SA Rutjes , Increased hepatitis E virus prevalence on Dutch pig farms from 33 to 55% by using appropriate internal quality controls for RT-PCR. Journal of Virological Methods 2007; 143: 112116.

133. C Seminati , Distribution of hepatitis E virus infection and its prevalence in pigs on commercial farms in Spain. Veterinary Journal 2008; 175: 130132.

136. JM Mansuy , High prevalence of anti-hepatitis E virus antibodies in blood donors from South West France. Journal of Medical Virology 2008; 80: 289293.

139. SP Sylvan , SH Jacobson , B Christenson . Prevalence of antibodies to hepatitis E virus among hemodialysis patients in Sweden. Journal of Medical Virology 1998; 54: 3843.

141. M Pavia , Prevalence of hepatitis E antibodies in healthy persons in southern Italy. Infection 1998; 26: 3235.

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