Autochthone Hepatitis-E-Virus-Infektion als Ursache der akuten Hepatitis in Deutschland – eine Kasuistik

Zusammenfassung

Während das Hepatitis-E-Virus (HEV) als Auslöser akuter Hepatitiden in tropischen und subtropischen Regionen Asiens, Afrikas und Amerikas mit niedrigem hygienischen Standard bekannt ist, werden in hoch entwickelten Industriestaaten zunehmend häufig autochthon erworbene Infektionen beobachtet. Bei 2 Patienten aus Thüringen ohne entsprechende Reiseanamnese wurden nach Ausschluss häufiger Hepatitis-Ursachen HEV-Infektionen diagnostiziert. Während beide Patienten einen ausgeprägten Transaminasenanstieg zeigten, war nur bei einem Patienten ein passagerer Ikterus nachweisbar. Bei beiden Patienten kam es im Verlauf zu einer vollständigen Restitutio ad integrum. Sowohl die Ergebnisse der phylogenetischen Analyse von Virusisolaten als auch epidemiologische Daten des Robert Koch-Instituts und der Gesundheitsämter zeigen, dass die Hepatitis E in Deutschland als Zoonose aufzufassen ist. Die Übertragung auf den Menschen erfolgt am wahrscheinlichsten über ungenügend gegartes Fleisch und Innereien von Hausschweinen und Wildtieren. Die Hepatitis E stellt eine wesentliche Differenzialdiagnose der akuten Non-A, B, C-Virus-Hepatitis dar. Wissenschaftliche Bemühungen sollten neben der exakten Erfassung von Erregerreservoirs und Transmissionswegen auf Konzepte zur Prophylaxe – insbesondere für Risikogruppen wie chronisch Leberkranke und Transplantierte – fokussieren.

Abstract

There is an increasing body of evidence that hepatitis E virus (HEV) triggers acute hepatitis not only in tropical and subtropical regions of Asia, Africa, and America with low sanitary standards but also in highly industrialized countries. We here report on two patients from Thuringia (Germany) with a HEV infection without a recent stay abroad. All other common causes of hepatitis were excluded. Transaminases were significantly incresed in both cases, while icterus could be proven in one patient, only. Both patients fully recovered in the long-term course. Epidemiological and phylogenetic data from viral analyses suggest that HEV infection has to be considered as a zoonosis. It is likely that viral transmission from animals to humans occurs through insufficiently cooked meat or entrails, e. g., from pigs or wild animals. In summary, HEV infection is a relevant differential diagnosis in acute non-A/B/C viral hepatitis. Further studies are required for the identification of other transmission pathways, pathogen reservoirs as well as novel concepts for prophylaxis, especially for patients at risk for hepatic diseases.

Hepatitis E - Deutschland - autochthone Hepatitis - akute Hepatitis

hepatitis E - Germany - autochthonous hepatitis - acute hepatitis

Literatur

• 1 Mushawar I K, Dawson G J, Bile K M et al. Serological studies of an enterically transmitted non-A, non-B hepatitis in Somalia.  J Med Virol. 1993;  40 218-221
• 2 Panda S K, Thrakral D, Rehman S. Hepatitis E virus.  Rev Med Virol. 2007;  17 151-180
• 3 Mushawar I K. Hepatitis E Virus: molecular virology, clinical features, diagnosis, transmission, epidemiology and prevention.  J Med Virol. 2008;  80 646-658
• 4 Aggarwal R, Naik S. Epidemiology of hepatitis E: Current status.  J Gastroenterol Hepatol. 2009;  24 1484-1493
• 5 Purcell R H, Emerson S U. Hepatitis E: An emerging awareness of an old disease.  J Hepatol. 2008;  48 494-503
• 6 Teich N, Tannapfel A, Ammon A et al. Sporadische Hepatitis E in Deutschland: eine zu selten erkannte Erkrankung.  Z Gastroenterol. 2003;  41 419-423
• 7 Meng X J, Purcell R H, Halbur P G et al. A novel virus in swine is closely related to the human hepatitis E virus.  Proc Natl Acad Sci USA. 1997;  94 9860-9865
• 8 Yazaki Y Mizuo H, Takahashi M, Sasaki N et al. Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be foodborne, as suggested by the presence of HEV in pig liver as food.  J Gen Virol. 2003;  84 2352-2357
• 9 Feagins A R, Opriessnig T, Guenette T K et al. Detection and characterization of infectious hepatitis E virus from commercial pig livers sold in local grocery stores in the USA.  J Gen Virol. 2001;  88 912-917
• 10 Tei S, Kitajima N, Takahashi K et al. Zoonotic transmission of hepatitis E virus from deer to human beings.  Lancet. 2003;  362 371-373
• 11 Takahashi K, Kitajima N, Abe N et al. Complete or near complete sequences of hepatitis E virus genome recovered from a wild boar, a deer and four patients who ate the deer.  Virology. 2004;  330 501-505
• 12 Tei S, Naoto K, Ohara S et al. Consumption of uncooked deer meat as a risk factor for hepatitis E virus infection: an age- and sex-matched case-control study.  J Med Virol. 2004;  74 67-70
• 13 Li T C, Chijiwa K, Sera N et al. Hepatitis E virus transmission from a wild boar meat.  Emerg Infect Dis. 2005;  11 1958-1960
• 14 Khuroo M S, Teli M R, Skidmore S et al. Incidence and severity of viral hepatitis in pregnancy.  Am J Med. 1981;  70 252-255
• 15 Haagsma E B, Berg A P, Porte R J et al. Chronic hepatitis E virus infection in liver transplant recipients.  Liver Transpl. 2008;  14 547-553
• 16 Kamar van den N, Mansuy J M, Cointault O et al. Hepatitis E virus-related cirrhosis in kidney- and kidney-pancreas-transplant recipients.  Am J Transplant. 2008;  8 1744-1748
• 17 Emerson S U, Anderson D, Arankalle A. et al .Hepevirus. In Fauquet C M, Mayo M A, Maniloff J Virus Taxonomy, VIIIth Report of the ICTV.. London: Elsevier/Academic Press; 2005: 853-857
• 18 Büchen-Osmond C, (Editor). Index of Viruses – Hepevirus. In ICTVdB – The Universal Virus Database, version 4.. New York, USA: Columbia University; 2006. http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_index.htm
• 19 Chandra V, Taneja S, Kalia M et al. Molecular biology and pathogenesis of hepatitis E virus.  J Biosci. 2008;  33 451-464
• 20 Dalton H R, Stableforth W, Thurairaja P et al. Autochthonous hepatitis E in Southwest England: natural history complications and seasonal varation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patientns with chronic liver disease.  Eur J Gastroenterol Hepatol. 2008;  20 784-790
• 21 Dalton H R, Bendall R, Ijaz S et al. Hepatitis E: an emerging infection in developed countries.  Lancet Infect Dis. 2008;  8 698-709
• 22 Bericht aus dem Fachgebiet 35 „Gastrointestinale Infektionen, Zoonosen und tropische Infektionen” des Robert-Koch-Institutes. Hepatitis E – Epidemiologie und Risikofaktoren in Deutschland. Epidemiologisches Bulletin Nr. 49; 2008
• 23 Bendall R, Ellis V, Ijaz S et al. Serological response to hepatitis E virus genotype 3 infection: IgG quantitation, avidity and IgM response.  J Med Virol. 2008;  80 95-101
• 24 Adelhoch C, Kaiser M, Pauli G et al. Indigenous hepatitis E virus infection of plasma donor in Germany.  Vox Sanguinis. 2009;  97 303-308
• 25 Lewis H C, Wichmann O, Duizer E. Transmission routes and risk factors for autochthonous hepatitis E virus infection in Europe: a systematic review.  Epidemio Infect. 2010;  138 145-166
• 26 Chapman B A, Burt M J, Wilkinson I D et al. Community acquired viral hepatitis in New Zealand: a case of sporadic hepatitis E virus infection.  Aust N Z J Med. 1993;  23 722-723
• 27 Heath T C, Burrow J N et al. Locally acquired hepatitis E in Northern Territory of Australia.  Med J Aust. 1995;  162 318-319
• 28 Ijaz S, Arnold E, Banks M et al. Non-travel-associated hepatitis E in England and Wales: demographic, clinical and molecular epidemiological characteristics.  J Infect Dis. 2005;  192 1166-1172
• 29 Widdowson M A, Jaspers W J, Poel W H et al. Cluster of cases of acute hepatitis associated with hepatitis E virus infection acquired in the Netherlands.  Clin Infect Dis. 2003;  36 29-33
• 30 Dalton H R, Hazeldine van der S, Banks M et al. Locally acquired hepatitis E in chronic liver disease.  Lancet. 2007;  369 1260
• 31 Gerolami R, Moal V, Colson P. Chronic hepatitis E with cirrhosis in a kidney-transplant recipient.  N Eng J Med. 2008;  358 811-817
• 32 Chauhan A, Jameel S, Dilawari J B et al. Hepatitis E virus transmission to a volunteer.  Lancet. 1993;  341 149-150
• 33 Knödler B, Hiller J, Löliger C C et al. Hepatitis E antibodies in blood donors, hemodialysis patients and normal people.  Beitr Infusionsther Transfusionsmed. 1994;  32 124-127
• 34 Nübling M, Hofmann F, Tiller F W. Occupational risk for hepatitis A and hepatitis E among health care professional.  Infection. 2002;  30 94-97
• 35 Rutjes S A, Lodder W J, Bouwknegt M et al. Increased hepatitis E virus prevalence in Dutch pig farms from 33 to 55 % by using appropriate internal quality controls for RF-PCR.  J Vitol Methods. 2007;  143 112-116
• 36 Preiss J C, Plentz A, Engelmann E et al. Autochthonous hepatitis E virus infection in Germany with sequence similarities to other European isolates.  Infection. 2006;  34 173-175
• 37 Schielke A, Sachs K, Lierz M et al. Detection of hepatitis E virus in wild boars of rural and urban regions in Germany and whole genome characterization of an endemic strain.  Virol J. 2009;  6 58
• 38 Baechlein C, Schielke A, Johne R et al. Prevalence of hepatitis E virus-specific antibodies in sera of German domestic pigs estimated by using different assays. Vet Microbiol. article in press 2009 DOI: 10.1016 /j.vetmic2009.12.011
• 39 Herremans M, Vennema H, Bakker J et al. Swine-like hepatitis E viruses are a cause of unexplained hepatitis in the Netherlands.  J Viral hepat. 2007;  14 140-146
• 40 Balayan M S, Usmanov R K, Zamyatina N A et al. Brief report: experimental hepatitis E infection in domestic pigs.  J Med Virol. 1990;  32 58-59
• 41 Meng X J, Halbur P G, Shapiro M S et al. Genetic and experimental evidence for cross-species infection by swine hepatitis E virus.  J Virol. 1998;  72 9714-9721
• 42 Wichmann O, Schimanski S, Koch J et al. Phylogenetic case control-study on hepatitis E infection in Germany.  J Infect Dis. 2008;  198 1732-1741
• 43 Feagins A R, Opriessnig T, Guenette D K et al. Inactivation of infectious hepatitis E virus present in commercial pig livers sold in local grocery stores in the United States.  Int J Food Microbiol. 2008;  123 32-37
• 44 Shrestha M P, Scott R M, Joshi D M et al. Safety and efficacy of a recombinant hepatitis E vaccine.  N Engl J Med. 2007;  356 895-903
• 45 Zhang J, Liu C B, Li R C et al. Randomized-controlled phase II clinical trial of a bacterially expressed recombinant hepatitis E vaccine.  Vaccine. 2009;  27 1869-1874