Hepatitis E Virus Detection in Liver Tissue from Patients with Suspected Drug-Induced Liver Injury

Hepatitis E virus (HEV) infection is increasingly recognized as a cause of acute hepatitis in the industrialized world. We aimed to determine the frequency of acute Hepatitis E virus (HEV) infection in cases of suspected drug-induced liver injury (DILI), mainly a diagnosis of exclusion. To this aim, formalin-fixed, paraffin-embedded (FFPE) liver tissues of all cases routinely processed in our institute during a 2 ½ years period in which DILI was amongst the differential diagnoses (157 liver biopsies, one liver explant) were subjected to semi-nested RT-PCR for the detection of hepatitis E virus (HEV) RNA. Histopathology was re-evaluated on all cases tested positive. HEV RNA was detectable in three of 158 cases (2%) tested, comprising autochthonic as well as travel-related infections with genotypes 1, 3, and 4 each found once, respectively. Histopathologic findings comprised one case with subtotal hepatic necrosis and two cases of acute (cholestatic) hepatitis not distinguishable from acute hepatitis of other etiology. Thus, the overall frequency of acute hepatitis E virus (HEV) infection as determined by detection of hepatitis E virus (HEV) RNA in liver tissue is substantially increased in patients with suspected drug-induced liver injury compared to the healthy population, emphasizing the need to actively look for hepatitis E virus (HEV) infection in cases of suspected drug-induced liver injury (DILI). Molecular testing for hepatitis E virus (HEV) RNA in routinely processed formalin-fixed, paraffin-embedded (FFPE) liver tissues can be applied to cases with undetermined hepatitis E virus (HEV) status

PCR detection and analyzis of potentially zoonotic Hepatitis E virus in French rats

BACKGROUND: Hepatitis E virus has been detected in a wide range of animals. While Genotypes 1-2 of this virus infect only humans, 3-4 can spread from animals to humans and cause sporadic cases of human disease. Pig, and possibly also rats, may act as a reservoir for virus. From a public health perspective it is important to clarify the role of rats for infection of humans. Rats often live close to humans and are therefore of special interest to public health. Rats live of waste and inside the sewage system and may become infected. Reports of hepatitis E virus in rats have been published but not from France. The possibility that rats in an urban area in France were Hepatitis E virus infected, with which type and relationship to other strains was investigated. This study provides information important to public health and better understanding the occurrence of hepatitis E virus in the environment. Eighty one rats (Rattus Norvegicus) were captured, euthanized, sampled (liver and faeces) and analyzed by real-time RT-PCR’s, one specific for Hepatitis E virus in rats and one specific for genotype 1-4 that that is known to infect humans. Positive samples were analyzed by a nested broad spectrum RT-PCR, sequenced and compared with sequences in Genbank. FINDINGS: Twelve liver and 11 faeces samples out of 81 liver and 81 faeces samples from 81 captured rats were positive in the PCR specific for Hepatitis E virus in rats and none in the PCR specific for genotype 1-4. Comparison by nucleotide BLAST showed a maximum of 87% similarity to Hepatitis E virus previously detected in rats and significantly less to genotype 1-4. CONCLUSIONS: This is the first study demonstrating that rats in France carries hepatitis E virus and provide information regarding its relation to other virus strains previously detected in rats and other host animals world-wide. Genotype 1-4 was not detected

Molecular features of hepatitis E virus from farmed rabbits in Shandong province, China

[EN] This study was undertaken to investigate the genetic variability of hepatitis E virus (HEV) from farmed rabbits in Shandong province, China. A total of 50 fresh faecal samples from 5 rabbit farms were collected and subjected to reverse transcription and nested polymerase chain reaction (RT-nPCR) for a fragment sequence of HEV capsid gene. The results demonstrated that HEV RNA was observed in 6 faecal samples (6/50, 12.0%). In addition, the result of phylogenetic analysis showed that the 6 HEV isolates were classified into HEV-3 genotype with other rabbit HEV isolates from other countries, and shared 85.2-87.2%, 81.5-83.1%, and 77.0-78.6% nucleotide similarities with rabbit HEV isolates from Korea, the United States and France, respectively. To sum up, the HEV isolated in this study from farmed rabbits belongs to the HEV-3 genotype, and the zoonotic ability and pathogenesis of the rabbit HEV merit further study due to the fact that HEV-3 genotype has the potential to trigger zoonotic infections.This study was supported by the Intramural Fund of Hebei University of Economics and Business in 2018 (2018PY17) and the Development Plan of Science and Technology of Tai’an, China (2016NS1051)Zhang, H.; Zhou, Y.; Liu, J. (2018). Molecular features of hepatitis E virus from farmed rabbits in Shandong province, China. World Rabbit Science. 26(4):307-312. https://doi.org/10.4995/wrs.2018.10225SWORD307312264Ahn H.S., Park B.J., Han S.H., Kim Y.H., Kim D.H., Kim B.S., Lee J.B., Park S.Y., Song C.S., Lee S.W., Choi I.S. 2017. Prevalence and genetic features of rabbit hepatitis E virus in Korea. J. Med. Virol., 89: 1995-2002. https://doi.org/10.1002/jmv.24875Burt S.A., Veltman J., Hakze-van der Honing R., Schmitt H., Poel W.H. 2016. Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands. Food Environ. Virol., 84: 313. https://doi.org/10.1007/s12560-016-9257-1Cossaboom C.M., Córdoba L., Dryman B.A., Meng X.J. 2011. Hepatitis E virus in rabbits, Virginia, USA. Emerg. Infect. Dis., 17: 2047-2049. https://doi.org/10.3201/eid1711.110428Cossaboom C.M., Córdoba L., Cao D., Ni Y.Y., Meng X.J. 2012. Complete genome sequence of hepatitis E virus from rabbits in the United States. J. Virol., 86: 13124-13125. https://doi.org/10.1128/JVI.02414-12Di Bartolo I., De Sabato L., Marata A., Martinelli N., Magistrali C., Monini M., Ponterio E., Ostanello F., Ruggeri F. 2016. Serological survey of hepatitis E virus infection in farmed and pet rabbits in Italy. Arch. Virol., 161: 1343-1346. https://doi.org/10.1007/s00705-016-2778-yEiden M., Vina-Rodriguez A., Schlosser J., Schirrmeier H., Groschup M.H. 2016. Detection of Hepatitis E Virus in Archived Rabbit Serum Samples, Germany 1989. Food Environ. Virol., 8: 105-107. https://doi.org/10.1007/s12560-015-9222-4Emerson S.U., Purcell R.H. 2003. Hepatitis E virus. Rev. Med.Virol., 13: 145-154. https://doi.org/10.1002/rmv.384Frias M., López-López P., Rivero A., Rivero-Juarez A. 2018. Role of Hepatitis E Virus Infection in Acute-on-Chronic Liver Failure. Biomed. Res. Int., 9098535. https://doi.org/10.1155/2018/9098535Fujiwara S., Yokokawa Y., Morino K., Hayasaka K., Kawabata M., Shimizu T. 2014. Chronic hepatitis E: a review of the literature. J. Viral Hepat., 21: 78-89. https://doi.org/10.1111/jvh.12156Geng J., Wang L., Wang X., Fu H., Bu Q, Liu P., Zhu Y., Wang M., Sui Y., Zhuang H. 2011. Potential risk of zoonotic transmission from young swine to human: seroepidemiological and genetic characterization of hepatitis E virus in human and various animals in Beijing, China. J. Viral Hept., 18: 583-590. https://doi.org/10.1111/j.1365-2893.2011.01472.xHuang F., Li Y., Yu W., Jing S., Wang J., Long F., He Z., Yang C., Bi Y., Cao W., Liu C., Hua X., Pan Q. 2016. Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis. Hepatology, 64: 350-359. https://doi.org/10.1002/hep.28668Izopet J., Dubois M., Bertagnoli S., Lhomme S., Marchandeau S., Boucher S., Kamar N., Abravanel F., Guérin J.L. 2012. Hepatitis E virus strains in rabbits and evidence of a closely related strain in humans, France. Emerg. Infect. Dis., 18: 1274-1281. https://doi.org/10.3201/eid1808.120057Jirintai S., Manglai D., Takahashi M., Nagashima S., Kobayashi T., Nishizawa T., Okamoto H. 2012. Molecular analysis of hepatitis E virus from farm rabbits in Inner Mongolia, China and its successful propagation in A549 and PLC/PRF/5 cells. Virus Res., 170: 126-137. https://doi.org/10.1016/j.virusres.2012.09.015Johne R., Dremsek P., Reetz J., Heckel G., Hess M., Ulrich R.G. 2014. Hepeviridae: an expanding family of vertebrate viruses. Infect. Genet. Evol., 27: 212-229. https://doi.org/10.1016/j.meegid.2014.06.024Kaiser M., Delaune D., Chazouillères O., Blümel J., Roque-Afonso A.M., Baylis S.A. 2018. A World Health Organization Human Hepatitis E Virus Reference Strain Related to Similar Strains Isolated from Rabbits. Genome Announc., 6: e00292-18. https://doi.org/10.1128/genomeA.00292-18Kamar N., Selves J., Mansuy J.M., Ouezzani L., Peron J.M., Guitard J., Cointault O., Esposito L., Abravanel F., Danjoux M., Durand D., Vinel J.P., Izopet J., Rostaing L. 2008. Hepatitis E virus and chronic hepatitis in organtransplant recipients. N. Engl. J. Med., 358: 811-817. https://doi.org/10.1056/NEJMoa0706992King N.J., Hewitt J., Perchec-Merien A.M. Hiding in Plain Sight? It's Time to Investigate Other Possible Transmission Routes for Hepatitis E Virus (HEV) in Developed Countries. Food Environ. Virol., 10: 225-252. https://doi.org/10.1007/s12560-018-9342-8Krzowska-Firych J.M., Lucas C., Lucas G., Tomasiewicz K. 2018. Hepatitis E-A new era in understanding. Ann. Agric. Environ. Med., 25: 250-254. https://doi.org/10.26444/aaem/75142Lee G.H., Tan B.H., Teo E.C., Lim S.G., Dan Y.Y., Wee A., Aw P.P., Zhu Y., Hibberd M.L., Tan C.K., Purdy M.A., Teo C.G. 2016. Chronic Infection With Camelid Hepatitis E Virus in a Liver Transplant Recipient Who Regularly Consumes Camel Meat and Milk. Gastroenterology, 150: 355-357. https://doi.org/10.1053/j.gastro.2015.10.048Lhomme S., Dubois M., Abravanel F., Top S., Bertagnoli S., Guerin J.L., Izopet J. Risk of zoonotic transmission of HEV from rabbits. J. Clin. Virol., 58: 357-362. https://doi.org/10.1016/j.jcv.2013.02.006Lhomme S., Top S., Bertagnoli S., Dubois M., Guerin J.-L., Izopet J. 2015. Wildlife reservoir for hepatitis E virus, Southwestern France. Emerg Infect. Dis., 21: 1224. https://doi.org/10.3201/eid2107.141909Li S., Liu M., Cong J., Zhou Y., Miao Z. 2017. Detection and characterization of Hepatitis E Virus in goats at slaughterhouse in Tai'an Region, China. Biomed. Res. Int., 3723650. https://doi.org/10.1155/2017/3723650Liu P., Bu Q.N., Wang L., Han J., Du R.J., Lei Y.X., Ouyang Y.Q., Li J., Zhu Y.H., Lu F.M. 2013. Transmission of hepatitis E virus from rabbits to cynomolgus macaques. Emerg. Infect. Dis., 19: 559-565. https://doi.org/10.3201/eid1904.120827Meng X.J. 2010a. Hepatitis E virus: animal reservoirs and zoonotic risk. Vet. Microbiol., 140: 256-265. https://doi.org/10.1016/j.vetmic.2009.03.017Meng X.J. 2010b. Novel strains of hepatitis E virus identified from humans and other animal species: is hepatitis E a zoonosis? J. Hepatol., 33: 842-845. https://doi.org/10.1016/S0168-8278(00)80319-0Meng X.J. 2011. From barnyard to food table: the omnipresence of hepatitis E virus and risk for zoonotic infection and food safety. Virus Res., 161: 23-30. https://doi.org/10.1016/j.virusres.2011.01.016Pavio N., Meng X.J., Doceul V. 2015. Zoonotic origin of hepatitis E. Curr. Opin. Virol., 10: 34-41. https://doi.org/10.1016/j.coviro.2014.12.006Pérez-Gracia M.T., Suay B., Mateos-Lindemann M.L. 2014. Hepatitis E: an emerging disease. Infect. Genet. Evol., 22: 40-59. https://doi.org/10.1016/j.meegid.2014.01.002Purcell R., Emerson S. 2008. Hepatitis E: an emerging awareness of an old disease. J. Hepatol., 48: 494-503. https://doi.org/10.1016/j.jhep.2007.12.008Purdy M.A., Khudyakov Y.E. 2010. Evolutionary history and population dynamics of hepatitis E virus. PLoS One, 5:e14376. https://doi.org/10.1371/journal.pone.0014376Ryll R., Eiden M., Heuser E., Weinhardt M., Ziege M., Höper D., Groschup M.H., Heckel G., Johne R., Ulrich R.G. 2018. Hepatitis E virus in feral rabbits along a rural-urban transect in Central Germany. Infect. Genet Evol., 61: 155-159. https://doi.org/10.1016/j.meegid.2018.03.019Shuai J.B., Li L.H., Li A.Y., He Y.Q., Zhang X.F. 2017. Full genome analysis of swine genotype 3 hepatitis E virus isolated from eastern China. J. Zhejiang Univ. Sci. B, 18: 549-554. https://doi.org/10.1631/jzus.B1600419Smith D.B., Simmonds P. 2014. International Committee on Taxonomy of Viruses Hepeviridae Study G., Jameel S., Emerson S.U., Harrison T.J., Meng X.J., Okamoto H., Van der Poel W.H., Purdy M.A. Consensus proposals for classification of the family Hepeviridae. J. Gen. Virol., 95: 2223-2232. https://doi.org/10.1099/vir.0.068429-0Sridhar S., Teng J.L.L., Chiu T.H., Lau S.K.P., Woo P.C.Y. 2017. Hepatitis E Virus Genotypes and Evolution: Emergence of Camel Hepatitis E Variants. Int. J. Mol. Sci., 18: E869. https://doi.org/10.3390/ijms18040869Syed S.F., Zhao Q., Umer M., Alagawany M., Ujjan I.A., Soomro F., Bangulzai N., Baloch A.H, Abd El-Hack M., Zhou E.M. 2018. Past, present and future of hepatitis E virus infection: Zoonotic perspectives. Microb. Pathog., 119: 103-108. https://doi.org/10.1016/j.micpath.2018.03.051Tei S., Kitajima N., Takahashi K., Mishiro S. 2003. Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet, 362: 371-373. https://doi.org/10.1016/S0140-6736(03)14025-1Wang L., Gong W., Fu H., Li M., Zhang Y., Luo Z., Xu Q., Wang L. 2018. Hepatitis E virus detected from Chinese laboratory ferrets and farmed mink. Transbound Emerg. Dis., 65: 219-223. https://doi.org/10.1111/tbed.12720Woo P.C., Lau S.K., Teng J.L., Tsang A.K., Joseph M., Wong E.Y., Tang Y., Sivakumar S., Xie J., Bai R., Wernery R., Wernery U., Yuen K.Y. 2014. New hepatitis E virus genotype in camels, the Middle East. Emerg .Infect. Dis., 20: 1044-1048. https://doi.org/10.3201/eid2006.140140Xia J., Zeng H., Liu L., Zhang Y., Liu P., Geng J., Wang L., Wang L., Zhuang H. 2015. Swine and rabbits are the main reservoirs of hepatitis E virus in China: detection of HEV RNA in feces of farmed and wild animals. Arch. Virol., 160: 2791-2798. https://doi.org/10.1007/s00705-015-2574-0Yazaki Y., Mizuo H., Takahashi M., Nishizawa T., Sasaki N., Gotanda Y., Okamoto H. 2003. Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food. J. Gen. Virol., 84: 2351-2357. https://doi.org/10.1099/vir.0.19242-0Zhang X.X., Qin S.Y., Zhang Y., Meng Q.F., Jiang J., Yang G.L., Zhao Q., Zhu X.Q. 2015. First report of hepatitis E virus infection in sika deer in China. Biomed. Res. Int., 502846. https://doi.org/10.1155/2015/502846Zhao C., Ma Z., Harrison T.J., Feng R., Zhang C., Qiao Z., Fan J., Ma H., Li M., Song A., Wang Y. 2009. A novel genotype of hepatitis E virus prevalent among farmed rabbits in China. J. Med. Virol., 81: 1371-1379. https://doi.org/10.1002/jmv.21536Zheng Y., Ge S., Zhang J., Guo Q., Ng M.H., Wang F., Xia N., Jiang Q. 2006. Swine as a principal reservoir of hepatitis E virus that infects humans in eastern China. J. Infect. Dis., 193: 1643-1649. https://doi.org/10.1086/50429

Hepatitis E virus mixed infection in immunocompetent patient

We detected 2 hepatitis E virus (HEV) strains in an acutely infected immunocompetent patient. Two populations of genotype 3 virus were observed in the hypervariable regions and open reading frames 2 and 3, indicating multiple infection with hepatitis E virus. Persons with mixed infections may provide the opportunity for virus recombination

Food Safety Risks Associated with Hepatitis E Virus Detection in Wild Boar Liver

Hepatitis E virus (HEV) has significantly impacted humans due to its potential to cause acute viral hepatitis. Discovery of hepatitis E virus in domestic pigs and wild boars worldwide and the realization that it is highly prevalent, raised concerns of the implications for food-borne transmission of HEV in Europe. Present work focusses on molecular detection of hepatitis E virus in wild boar liver samples, underlining the possible role of wildlife as a source of HEV transmission to humans. During hunting season 2016-2017, liver samples were collected from 37 wild boars in Iași and Suceava County. All tissues samples were submitted for RNA isolation followed by nested RT-PCR. Genetic characterization of wild boar HEV targeted the structural gene in the ORF2 region of hepatitis E virus genome. After specific amplification by nested RT-PCR of a 348 nt fragment from HEV ORF2, five liver samples positive for hepatitis E virus genotype 3 RNA were identified. In the present study HEV detection in Romanian fresh liver from wild boars highlights the importance of swine as a possible source of foodborne transmission. Moreover, our results along with the reviewed literature data emphasize the necessity of efficient food safety control measures implementation

Porcine Hepatitis E

Hepatitis E virus (HEV) is a zoonotic agent that can be transmitted from pigs to humans via consumption of pork and products derived of it. Recently, the European Food Safety Authority (EFSA) has published a scientific opinion urging for measures to prevent Hepatitis E virus (HEV) from entering the food chain

Hepatite E Aguda Severa em Mulher com História Auto-Imune

Hepatitis E virus genotype 3 infections are normally asymptomatic in immunocompetent individuals. Symptomatic cases of acute icteric hepatitis E are seldom observed among women, younger men and children but are particularly seen in middle-aged/elderly men. We report a case of severe acute hepatitis E caused by genotype 3 in an immunocompetent 40-year-old woman that required prolonged hospitalization. Her medical history included an autoimmune background, namely atrophic gastritis and Graves' disease. She presented an extensive hepatic necrosis as revealed by the high levels of aminotransferases (ALT 4893 U/L; AST 3138 U/L). She showed also a coagulation disorder (prothrombin time; INR = 1.33). Serological markers for hepatitis viruses A, B and C were negative but serum was positive for hepatitis E virus RNA. Sequencing and phylogenetic analysis revealed that the hepatitis E virus strain belonged to subgenotype 3a. This is suggestive of an association between the severe acute hepatitis E virus genotype 3 infection and the autoimmune background.info:eu-repo/semantics/publishedVersio

Hepatitis E Virus

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the developing world. It is a waterborne virus that can cause epidemics in the face of overcrowding and poor sanitation. Although the hepatitis illness is usually self-limiting, it has a high mortality in pregnant women and can become a chronic infection in the immunosuppressed. Treatment is mostly supportive and prevention is by good water hygiene

Dengue and hepatitis E virus infection in pregnant women in Eastern Sudan, a challenge for diagnosis in an endemic area

Dengue fever and hepatitis E virus infection are both a public health problem in developing countries due to poor sanitation. Infection with viral hepatitis and dengue fever can present with similar clinical such and fever, headache and abortion. This study was conducted in Port-Sudan city in the eastern part of the country. ELISA and Real Time PCR tests were used to detect the infection. A total number of 39 pregnant women with a mean age 26 ±7.8 were included in the study. All of them had fever, 32 (92.3%) admitted with headache, 11 (28.2%) of them had vomiting, and abortion was reported in two cases (5.1%). The study showed that 4 ( 10.3% ) of pregnant women were positive for the Hepatitis E virus, 5 ( 12.8%) positive for Dengue virus IgG, and only one sample (2.6%) was positive for IgM capture ELISA and real time PCR . Death due to hepatitis E infection was reported in one case with 7th month of pregnancy. Most of hepatitis cases were reported in the central sector of the Portsudan city. The diagnosis of hepatitis E virus and dengue virus in an endemic area is a great challenge for health care staff working in these areas. Both Dengue virus and Hepatitis E virus infection should be considered in pregnant women especially in similar settings