Abstract
Hepatitis E is an important public health disease in many developing countries of Asia and Africa with large explosive outbreaks. The disease is also endemic with sporadic or clustered cases in many industrialized countries. The causative agent, hepatitis E virus (HEV), is a small nonenveloped positive-sense RNA virus that is currently classified in the family Hepeviridae. At least four recognized and two putative genotypes of mammalian HEV have been recognized: genotypes 1 and 2 HEV are restricted to humans and associated with epidemics, whereas genotypes 3 and 4 HEV are zoonotic and associated with sporadic and clustered cases. The life cycle and replication mechanism of HEV remain largely unknown. The genome of HEV consists of three open reading frames (ORF): ORF1 encodes nonstructural proteins involved in virus replication, ORF2 encodes the major capsid protein that induces neutralizing antibodies, and ORF3 encodes a small multifunctional protein. ORF2 and ORF3 overlap each other but neither overlaps ORF1, and the ORF2 and ORF3 proteins are translated from a single bicistronic mRNA. Waterborne transmission of HEV due to fecal contamination of water supplies is the most important route of spread, although other routes such as zoonotic, vertical, foodborne, and blood-borne transmissions have also been documented. In addition to the main clinical signs such as jaundice, anorexia, abdominal pain, nausea, vomiting, and fever, HEV infection has recently been linked to neurological symptoms, although the mechanism of neurotropic clinical manifestation remains unclear. The highest attack rate of clinical disease is in young adults of 20–29 years of age, although the seroprevalence of HEV increases with age. The mortality associated with HEV infection is generally <1 % in the general population, although a relatively high mortality rate of up to 25 % has been reported in infected pregnant women. Hepatitis E was thought to be an exclusively self-limiting acute disease; however, persistent and chronic hepatitis E cases have recently been reported in immunocompromised individuals such as organ transplant recipients. The genetic identification of numerous animal strains of HEV and the demonstrated ability of cross-species infection by these strains have not only broadened our understanding of the ecology and natural history of HEV but also raised important public health concerns for zoonotic HEV transmission and food safety. Pigs and likely other animal species such as deer and rabbits may serve as reservoirs for HEV. Animal handlers such as pig farmers and swine veterinarians have been identified as high-risk occupations and are at an increased risk of zoonotic exposure to HEV infection. The current available diagnostic assays for HEV are not standardized or approved by FDA, and consequently hepatitis E is underdiagnosed in industrialized countries. A vaccine against HEV was recently licensed for use in China, but is not yet available in other countries; protection of water from fecal contamination, practicing good hygiene, and avoiding consumption of raw animal meats are still the primary preventive measures. Pegylated interferon-α and ribavirin have been shown to induce a sustained inhibition of HEV and improve liver histology in infected patients and thus may serve as potential antiviral drugs.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Khuroo MS. Study of an epidemic of non-A, non-B hepatitis. Possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type. Am J Med. 1980;68:818–24.
Wong DC, Purcell RH, Sreenivasan MA, Prasad SR, Pavri KM. Epidemic and endemic hepatitis in India: evidence for a non-A, non-B hepatitis virus aetiology. Lancet. 1980;2:876–9.
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;247:1335–9.
Emerson S, Purcell RH. Hepatitis E virus. In: Fields B, Knipe DM, Howley PM, editors. Fields virology. 5th ed. Philadelphia: Wolters kluwer/Lippincott Williams & Wilkins; 2007. p. 3047–58.
Meng XJ. Recent advances in Hepatitis E virus. J Viral Hepat. 2010;17:153–61.
Meng XJ. Hepatitis E, virus: animal reservoirs and zoonotic risk. Vet Microbiol. 2010;140:256–65.
Meng XJ. Hepatitis E, as a zoonosis. In: Thomas HZ, Zuckermann A, Lemon S, editors. Viral hepatitis. 3rd ed. Oxford: Blackwell Publishing Ltd; 2006. p. 611–23.
Proffitt A. First HEV, vaccine approved. Nat Biotechnol. 2012;30:300.
Khuroo MS. Discovery of hepatitis E: the epidemic non-A, non-B hepatitis 30 years down the memory lane. Virus Res. 2011;161:3–14.
Vishwanathan R. Infectious hepatitis in Delhi (1955–56): a critical study: epidemiology. Indian J Med Res. 1957;45(Suppl):49–58.
Khuroo MS, Teli MR, Skidmore S, Sofi MA, Khuroo MI. Incidence and severity of viral hepatitis in pregnancy. Am J Med. 1981;70:252–5.
Balayan MS, Andjaparidze AG, Savinskaya SS, et al. Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology. 1983;20:23–31.
Bradley DW, Krawczynski K, Cook Jr EH, et al. Enterically transmitted non-A, non-B hepatitis: serial passage of disease in cynomolgus macaques and tamarins and recovery of disease-associated 27- to 34-nm viruslike particles. Proc Natl Acad Sci U S A. 1987;84:6277–81.
Arankalle VA, Ticehurst J, Sreenivasan MA, et al. Aetiological association of a virus-like particle with enterically transmitted non-A, non-B hepatitis. Lancet. 1988;1:550–4.
Arankalle VA, Chadha MS, Tsarev SA, et al. Seroepidemiology of water-borne hepatitis in India and evidence for a third enterically-transmitted hepatitis agent. Proc Natl Acad Sci U S A. 1994;91:3428–32.
Meng XJ, Purcell RH, Halbur PG, et al. A novel virus in swine is closely related to the human hepatitis E virus. Proc Natl Acad Sci U S A. 1997;94:9860–5.
Meng XJ. Novel strains of hepatitis E virus identified from humans and other animal species: is hepatitis E a zoonosis? J Hepatol. 2000;33:842–5.
Meng XJ. From barnyard to food table: the omnipresence of hepatitis E virus and risk for zoonotic infection and food safety. Virus Res. 2011;161:23–30.
Margolis HA, Alter MJ, Hadler SC. Viral hepatitis. In: Viral infections of humans: epidemiology and control. 4th ed. New York: Plenum Publishing Co; 1997.
Stoszek SK, Abdel-Hamid M, Saleh DA, et al. High prevalence of hepatitis E antibodies in pregnant Egyptian women. Trans R Soc Trop Med Hyg. 2006;100:95–101.
Bhatia V, Singhal A, Panda SK, Acharya SK. A 20-year single-center experience with acute liver failure during pregnancy: is the prognosis really worse? Hepatology. 2008;48:1577–85.
Navaneethan U, Al Mohajer M, Shata MT. Hepatitis E and pregnancy: understanding the pathogenesis. Liver Int. 2008;28:1190–9.
Sharapov MB, Favorov MO, Yashina TL, et al. Acute viral hepatitis morbidity and mortality associated with hepatitis E virus infection: Uzbekistan surveillance data. BMC Infect Dis. 2009;9:35.
Chadha MS, Walimbe AM, Arankalle VA. Retrospective serological analysis of hepatitis E patients: a long-term follow-up study. J Viral Hepat. 1999;6:457–61.
Christensen PB, Engle RE, Hjort C, et al. Time trend of the prevalence of hepatitis E antibodies among farmers and blood donors: a potential zoonosis in Denmark. Clin Infect Dis. 2008;47:1026–31.
Coursaget P, Buisson Y, Enogat N, et al. Outbreak of enterically-transmitted hepatitis due to hepatitis A and hepatitis E viruses. J Hepatol. 1998;28:745–50.
Khan A, Tanaka Y, Kurbanov F, et al. Investigating an outbreak of acute viral hepatitis caused by hepatitis E virus variants in Karachi, South Pakistan. J Med Virol. 2011;83:622–9.
Drobeniuc J, Favorov MO, Shapiro CN, et al. Hepatitis E virus antibody prevalence among persons who work with swine. J Infect Dis. 2001;184:1594–7.
Krumbholz A, Mohn U, Lange J, et al. Prevalence of hepatitis E virus-specific antibodies in humans with occupational exposure to pigs. Med Microbiol Immunol. 2012;201:239–44.
Meng XJ, Wiseman B, Elvinger F, et al. Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries. J Clin Microbiol. 2002;40:117–22.
Renou C, Lafeuillade A, Cadranel JF, et al. Hepatitis E virus in HIV-infected patients. AIDS. 2010;24:1493–9.
Shrestha MP, Scott RM, Joshi DM, et al. Safety and efficacy of a recombinant hepatitis E vaccine. N Engl J Med. 2007;356:895–903.
Zhu FC, Zhang J, Zhang XF, 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.
Kamar N, Bendall R, Legrand-Abravanel F, et al. Hepatitis E. Lancet. 2012;379:2477–88.
Ticehurst J, Popkin TJ, Bryan JP, et al. Association of hepatitis E virus with an outbreak of hepatitis in Pakistan: serologic responses and pattern of virus excretion. J Med Virol. 1992;36:84–92.
Gotanda Y, Iwata A, Ohnuma H, et al. Ongoing subclinical infection of hepatitis E virus among blood donors with an elevated alanine aminotransferase level in Japan. J Med Virol. 2007;79:734–42.
Takahashi M, Kusakai S, Mizuo H, et al. Simultaneous detection of immunoglobulin A (IgA) and IgM antibodies against hepatitis E virus (HEV) Is highly specific for diagnosis of acute HEV infection. J Clin Microbiol. 2005;43:49–56.
Bendall R, Ellis V, Ijaz S, Ali R, Dalton H. A comparison of two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developed countries. J Med Virol. 2010;82:799–805.
Mast EE, Alter MJ, Holland PV, Purcell RH. Evaluation of assays for antibody to hepatitis E virus by a serum panel. Hepatitis E Virus Antibody Serum Panel Evaluation Group. Hepatology. 1998;27:857–61.
Bryan JP, Tsarev SA, Iqbal M, et al. Epidemic hepatitis E in Pakistan: patterns of serologic response and evidence that antibody to hepatitis E virus protects against disease. J Infect Dis. 1994;170:517–21.
Goldsmith R, Yarbough PO, Reyes GR, et al. Enzyme-linked immunosorbent assay for diagnosis of acute sporadic hepatitis E in Egyptian children. Lancet. 1992;339:328–31.
Mushahwar IK, Dawson GJ, Bile KM, Magnius LO. Serological studies of an enterically transmitted non-A, non-B hepatitis in Somalia. J Med Virol. 1993;40:218–21.
Khuroo MS, Kamili S, Dar MY, Moecklii R, Jameel S. Hepatitis E and long-term antibody status. Lancet. 1993;341:1355.
Colson P, Borentain P, Queyriaux B, et al. Pig liver sausage as a source of hepatitis E virus transmission to humans. J Infect Dis. 2010;202:825–34.
Inoue J, Ueno Y, Nagasaki F, et al. Sporadic acute hepatitis E occurred constantly during the last decade in northeast Japan. J Gastroenterol. 2009;44:329–37.
Yazaki Y, Mizuo H, Takahashi M, et al. 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. 2003;84:2351–7.
Vivek R, Nihal L, Illiayaraja J, et al. Investigation of an epidemic of Hepatitis E in Nellore in south India. Trop Med Int Health. 2010;15:1333–9.
Wu KT, Chung KM, Feng IC, et al. Acute hepatitis E virus infection in Taiwan 2002–2006 revisited: PCR shows frequent co-infection with multiple hepatitis viruses. J Med Virol. 2009;81:1734–42.
Enouf V, Dos Reis G, Guthmann JP, et al. Validation of single real-time TaqMan PCR assay for the detection and quantitation of four major genotypes of hepatitis E virus in clinical specimens. J Med Virol. 2006;78:1076–82.
Jothikumar N, Cromeans TL, Robertson BH, Meng XJ, Hill VR. A broadly reactive one-step real-time RT-PCR assay for rapid and sensitive detection of hepatitis E virus. J Virol Methods. 2006;131:65–71.
Baylis SA, Hanschmann KM, Blumel J, Nubling CM. Standardization of hepatitis E virus (HEV) nucleic acid amplification technique-based assays: an initial study to evaluate a panel of HEV strains and investigate laboratory performance. J Clin Microbiol. 2011;49:1234–9.
Meng X, Anderson DA, Arankalle VA, Emerson SU, Harrison TJ, Jameel S, Okamoto H. H. Hepeviridae. In: King AA, Adams MJ, Carstens EB, Lefkowitz EJ, editors. Virus taxonomy, 9th report of the ICTV. London: Elsevier Academic Press; 2012. p. 1021–8.
Emerson SU, Arankalle VA, Purcell RH. Thermal stability of hepatitis E virus. J Infect Dis. 2005;192:930–3.
Feagins AR, Opriessnig T, Guenette DK, Halbur PG, Meng XJ. 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;123:32–7.
Haqshenas G, Shivaprasad HL, Woolcock PR, Read DH, Meng XJ. Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-splenomegaly syndrome in the United States. J Gen Virol. 2001;82:2449–62.
Guu TS, Liu Z, Ye Q, et al. Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding. Proc Natl Acad Sci U S A. 2009;106:12992–7.
Yamashita T, Mori Y, Miyazaki N, et al. Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure. Proc Natl Acad Sci U S A. 2009;106: 12986–91.
Xing L, Li TC, Mayazaki N, et al. Structure of hepatitis E virion-sized particle reveals an RNA-dependent viral assembly pathway. J Biol Chem. 2010;285:33175–83.
Haqshenas G, Huang FF, Fenaux M, et al. The putative capsid protein of the newly identified avian hepatitis E virus shares antigenic epitopes with that of swine and human hepatitis E viruses and chicken big liver and spleen disease virus. J Gen Virol. 2002;83:2201–9.
Guo H, Zhou EM, Sun ZF, Meng XJ, Halbur PG. Identification of B-cell epitopes in the capsid protein of avian hepatitis E virus (avian HEV) that are common to human and swine HEVs or unique to avian HEV. J Gen Virol. 2006;87:217–23.
Cossaboom CM, Cordoba L, Sanford BJ, et al. Cross-species infection of pigs with a novel rabbit, but not rat, strain of hepatitis E virus isolated in the United States. J Gen Virol. 2012;93:1687–95.
Ahmad I, Holla RP, Jameel S. Molecular virology of hepatitis E virus. Virus Res. 2011;161:47–58.
Huang YW, Opriessnig T, Halbur PG, Meng XJ. Initiation at the third in-frame AUG codon of open reading frame 3 of the hepatitis E virus is essential for viral infectivity in vivo. J Virol. 2007;81:3018–26.
Kabrane-Lazizi Y, Meng XJ, Purcell RH, Emerson SU. Evidence that the genomic RNA of hepatitis E virus is capped. J Virol. 1999;73:8848–50.
Graff J, Torian U, Nguyen H, Emerson SU. A bicistronic subgenomic mRNA encodes both the ORF2 and ORF3 proteins of hepatitis E virus. J Virol. 2006;80:5919–26.
Bilic I, Jaskulska B, Basic A, Morrow CJ, Hess M. Sequence analysis and comparison of avian hepatitis E viruses from Australia and Europe indicate the existence of different genotypes. J Gen Virol. 2009;90:863–73.
Johne R, Plenge-Bonig A, Hess M, Ulrich RG, Reetz J, Schielke A. Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR. J Gen Virol. 2010;91:750–8.
Purcell RH, Engle RE, Rood MP, et al. Hepatitis E virus in rats, Los Angeles, California, USA. Emerg Infect Dis. 2011;17:2216–22.
Takahashi M, Nishizawa T, Sato H, et al. Analysis of the full-length genome of a hepatitis E virus isolate obtained from a wild boar in Japan that is classifiable into a novel genotype. J Gen Virol. 2011;92:902–8.
Batts W, Yun S, Hedrick R, Winton J. A novel member of the family Hepeviridae from cutthroat trout (Oncorhynchus clarkii). Virus Res. 2011;158:116–23.
Tanaka T, Takahashi M, Kusano E, Okamoto H. Development and evaluation of an efficient cell-culture system for Hepatitis E virus. J Gen Virol. 2007;88:903–11.
Okamoto H. Efficient cell culture systems for hepatitis E virus strains in feces and circulating blood. Rev Med Virol. 2011;21:18–31.
Magden J, Takeda N, Li T, et al. Virus-specific mRNA capping enzyme encoded by hepatitis E virus. J Virol. 2001;75:6249–55.
Karpe YA, Lole KS. Deubiquitination activity associated with hepatitis E virus putative papain-like cysteine protease. J Gen Virol. 2011;92:2088–92.
Karpe YA, Meng XJ. Hepatitis e virus replication requires an active ubiquitin-proteasome system. J Virol. 2012;86:5948–52.
Karpe YA, Lole KS. NTPase and 5' to 3' RNA duplex-unwinding activities of the hepatitis E virus helicase domain. J Virol. 2010;84:3595–602.
Karpe YA, Lole KS. RNA 5'-triphosphatase activity of the hepatitis E virus helicase domain. J Virol. 2010;84:9637–41.
Pudupakam RS, Huang YW, Opriessnig T, Halbur PG, Pierson FW, Meng XJ. Deletions of the hypervariable region (HVR) in open reading frame 1 of hepatitis E virus do not abolish virus infectivity: evidence for attenuation of HVR deletion mutants in vivo. J Virol. 2009;83:384–95.
Pudupakam RS, Kenney SP, Cordoba L, et al. Mutational analysis of the hypervariable region of hepatitis e virus reveals its involvement in the efficiency of viral RNA replication. J Virol. 2011;85:10031–40.
Graff J, Zhou YH, Torian U, et al. Mutations within potential glycosylation sites in the capsid protein of hepatitis E virus prevent the formation of infectious virus particles. J Virol. 2008;82:1185–94.
Xing L, Wang JC, Li TC, et al. Spatial configuration of hepatitis E virus antigenic domain. J Virol. 2011;85:1117–24.
Kamili S. Toward the development of a hepatitis E vaccine. Virus Res. 2011;161:93–100.
Zafrullah M, Ozdener MH, Panda SK, Jameel S. The ORF3 protein of hepatitis E virus is a phosphoprotein that associates with the cytoskeleton. J Virol. 1997;71:9045–53.
Kenney SP, Pudupakam RS, Huang YW, Pierson FW, Leroith T, Meng XJ. The PSAP, motif within the ORF3 protein of an avian strain of the hepatitis E virus is not critical for viral infectivity in vivo but plays a role in virus release. J Virol. 2012;86:5637–46.
Billam P, Pierson FW, Li W, LeRoith T, Duncan RB, Meng XJ. Development and validation of a negative-strand-specific reverse transcription-PCR assay for detection of a chicken strain of hepatitis E virus: identification of nonliver replication sites. J Clin Microbiol. 2008;46:2630–4.
Williams TP, Kasorndorkbua C, Halbur PG, et al. Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model. J Clin Microbiol. 2001;39:3040–6.
Kalia M, Chandra V, Rahman SA, Sehgal D, Jameel S. Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection. J Virol. 2009;83:12714–24.
Surjit M, Jameel S, Lal SK. Cytoplasmic localization of the ORF2 protein of hepatitis E virus is dependent on its ability to undergo retrotranslocation from the endoplasmic reticulum. J Virol. 2007;81:3339–45.
Cao DM, Meng XJ. Molecular biology and replication of hepatitis E virus. Emerg Microbes Infect. 2012;1:e17.
Cao D, Huang YW, Meng XJ. The nucleotides on the stem-loop RNA structure in the junction region of the hepatitis E virus genome are critical for virus replication. J Virol. 2010;84:13040–4.
Yamada K, Takahashi M, Hoshino Y, et al. ORF3 protein of hepatitis E virus is essential for virion release from infected cells. J Gen Virol. 2009;90:1880–91.
Nakamura M, Takahashi K, Taira K, et al. Hepatitis E virus infection in wild mongooses of Okinawa, Japan: demonstration of anti-HEV antibodies and a full-genome nucleotide sequence. Hepatol Res. 2006;34:137–40.
Tei S, Kitajima N, Takahashi K, Mishiro S. Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet. 2003;362:371–3.
Zhao C, Ma Z, Harrison TJ, et al. A novel genotype of hepatitis E virus prevalent among farmed rabbits in China. J Med Virol. 2009;81:1371–9.
Cossaboom CM, Cordoba L, Dryman BA, Meng XJ. Hepatitis E virus in rabbits, Virginia, USA. Emerg Infect Dis. 2011;17:2047–9.
Arankalle VA, Chobe LP, Chadha MS. Type-IV Indian swine HEV infects rhesus monkeys. J Viral Hepat. 2006;13:742–5.
Meng XJ, Halbur PG, Shapiro MS, et al. Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. J Virol. 1998;72:9714–21.
Halbur PG, Kasorndorkbua C, Gilbert C, et al. Comparative pathogenesis of infection of pigs with hepatitis E viruses recovered from a pig and a human. J Clin Microbiol. 2001;39:918–23.
Feagins AR, Opriessnig T, Huang YW, Halbur PG, Meng XJ. Cross-species infection of specific-pathogen-free pigs by a genotype 4 strain of human hepatitis E virus. J Med Virol. 2008;80:1379–86.
Maneerat Y, Clayson ET, Myint KS, Young GD, Innis BL. Experimental infection of the laboratory rat with the hepatitis E virus. J Med Virol. 1996;48:121–8.
Huang FF, Sun ZF, Emerson SU, et al. Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV. J Gen Virol. 2004;85:1609–18.
Ma H, Zheng L, Liu Y, et al. Experimental infection of rabbits with rabbit and genotypes 1 and 4 hepatitis E viruses. PLoS One. 2010;5:e9160.
Teshale EH, Hu DJ. Hepatitis E: epidemiology and prevention. World J Hepatol. 2011;3:285–91.
Labrique AB, Zaman K, Hossain Z, et al. Epidemiology and risk factors of incident hepatitis E virus infections in rural Bangladesh. Am J Epidemiol. 2010;172:952–61.
Sailaja B, Murhekar MV, Hutin YJ, et al. Outbreak of waterborne hepatitis E in Hyderabad, India, 2005. Epidemiol Infect. 2009;137:234–40.
Guthmann JP, Klovstad H, Boccia D, et al. A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods. Clin Infect Dis. 2006;42:1685–91.
Dalton HR, Bendall R, Ijaz S, Banks M. Hepatitis E: an emerging infection in developed countries. Lancet Infect Dis. 2008;8:698–709.
Miyamura T. Hepatitis E, virus infection in developed countries. Virus Res. 2011;161:40–6.
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.
Merens A, Guerin PJ, Guthmann JP, Nicand E. Outbreak of hepatitis E virus infection in Darfur, Sudan: effectiveness of real-time reverse transcription-PCR analysis of dried blood spots. J Clin Microbiol. 2009;47:1931–3.
Howard CM, Handzel T, Hill VR, et al. Novel risk factors associated with hepatitis E virus infection in a large outbreak in northern Uganda: results from a case–control study and environmental analysis. Am J Trop Med Hyg. 2010;83:1170–3.
Teshale EH, Grytdal SP, Howard C, et al. Evidence of person-to-person transmission of hepatitis E virus during a large outbreak in Northern Uganda. Clin Infect Dis. 2010;50:1006–10.
Khuroo MS, Khuroo MS. Seroepidemiology of a second epidemic of hepatitis E in a population that had recorded first epidemic 30 years before and has been under surveillance since then. Hepatol Int. 2010;4:494–9.
Bile K, Isse A, Mohamud O, et al. Contrasting roles of rivers and wells as sources of drinking water on attack and fatality rates in a hepatitis E epidemic in Somalia. Am J Trop Med Hyg. 1994;51:466–74.
Ippagunta SK, Naik S, Sharma B, Aggarwal R. Presence of hepatitis E virus in sewage in Northern India: frequency and seasonal pattern. J Med Virol. 2007;79:1827–31.
Said B, Ijaz S, Kafatos G, et al. Hepatitis E outbreak on cruise ship. Emerg Infect Dis. 2009;15:1738–44.
Wedemeyer H, Pischke S, Manns MP. Pathogenesis and treatment of hepatitis e virus infection. Gastroenterology. 2012;142:1388–97.e1.
Harrison TJ. Hepatitis E, virus – an update. Liver. 1999;19:171–6.
Teshale EH, Howard CM, Grytdal SP, et al. Hepatitis E epidemic, Uganda. Emerg Infect Dis. 2010;16:126–9.
Rodriguez Lay Lde L, Quintana A, Villalba MC, et al. Dual infection with hepatitis A and E viruses in outbreaks and in sporadic clinical cases: Cuba 1998–2003. J Med Virol. 2008;80:798–802.
Albetkova A, Drobeniuc J, Yashina T, et al. Characterization of hepatitis E virus from outbreak and sporadic cases in Turkmenistan. J Med Virol. 2007;79:1696–702.
Maila HT, Bowyer SM, Swanepoel R. Identification of a new strain of hepatitis E virus from an outbreak in Namibia in 1995. J Gen Virol. 2004;85:89–95.
Corwin AL, Tien NT, Bounlu K, et al. The unique riverine ecology of hepatitis E virus transmission in South-East Asia. Trans R Soc Trop Med Hyg. 1999;93:255–60.
Corwin A, Putri MP, Winarno J, et al. Epidemic and sporadic hepatitis E virus transmission in West Kalimantan (Borneo), Indonesia. Am J Trop Med Hyg. 1997;57:62–5.
Withers MR, Correa MT, Morrow M, et al. Antibody levels to hepatitis E virus in North Carolina swine workers, non-swine workers, swine, and murids. Am J Trop Med Hyg. 2002;66: 384–8.
Pourpongporn P, Samransurp K, Rojanasang P, Wiwattanakul S, Srisurapanon S. The prevalence of anti-hepatitis E in occupational risk groups. J Med Assoc Thai. 2009;92 Suppl 3:S38–42.
Karetnyi YV, Gilchrist MJ, Naides SJ. Hepatitis E virus infection prevalence among selected populations in Iowa. J Clin Virol. 1999;14:51–5.
Vaidya SR, Tilekar BN, Walimbe AM, Arankalle VA. Increased risk of hepatitis E in sewage workers from India. J Occup Environ Med. 2003;45:1167–70.
Jeggli S, Steiner D, Joller H, Tschopp A, Steffen R, Hotz P. Hepatitis E, Helicobacter pylori, and gastrointestinal symptoms in workers exposed to waste water. Occup Environ Med. 2004;61:622–7.
Arankalle VA, Tsarev SA, Chadha MS, et al. Age-specific prevalence of antibodies to hepatitis A and E viruses in Pune, India, 1982 and 1992. J Infect Dis. 1995;171:447–50.
Lok AS, Kwan WK, Moeckli R, et al. Seroepidemiological survey of hepatitis E in Hong Kong by recombinant-based enzyme immunoassays. Lancet. 1992;340:1205–8.
Tanaka E, Matsumoto A, Takeda N, et al. Age-specific antibody to hepatitis E virus has remained constant during the past 20 years in Japan. J Viral Hepat. 2005;12:439–42.
Arankalle VA, Chadha MS, Chitambar SD, Walimbe AM, Chobe LP, Gandhe SS. Changing epidemiology of hepatitis A and hepatitis E in urban and rural India (1982–98). J Viral Hepat. 2001;8:293–303.
Rab MA, Bile MK, Mubarik MM, et al. Water-borne hepatitis E virus epidemic in Islamabad, Pakistan: a common source outbreak traced to the malfunction of a modern water treatment plant. Am J Trop Med Hyg. 1997;57:151–7.
Kumar A, Beniwal M, Kar P, Sharma JB, Murthy NS. Hepatitis E in pregnancy. Int J Gynaecol Obstet. 2004;85:240–4.
Patra S, Kumar A, Trivedi SS, Puri M, Sarin SK. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med. 2007;147:28–33.
Kasorndorkbua C, Guenette DK, Huang FF, Thomas PJ, Meng XJ, Halbur PG. Routes of transmission of swine hepatitis E virus in pigs. J Clin Microbiol. 2004;42:5047–52.
Pina S, Jofre J, Emerson SU, Purcell RH, Girones R. Characterization of a strain of infectious hepatitis E virus isolated from sewage in an area where hepatitis E is not endemic. Appl Environ Microbiol. 1998;64:4485–8.
Pina S, Buti M, Cotrina M, Piella J, Girones R. HEV identified in serum from humans with acute hepatitis and in sewage of animal origin in Spain. J Hepatol. 2000;33:826–33.
Feagins AR, Opriessnig T, Guenette DK, Halbur PG, Meng XJ. Detection and characterization of infectious Hepatitis E virus from commercial pig livers sold in local grocery stores in the USA. J Gen Virol. 2007;88:912–7.
Matsuda H, Okada K, Takahashi K, Mishiro S. Severe hepatitis E virus infection after ingestion of uncooked liver from a wild boar. J Infect Dis. 2003;188:944.
Li TC, Chijiwa K, Sera N, et al. Hepatitis E virus transmission from wild boar meat. Emerg Infect Dis. 2005;11:1958–60.
Tei S, Kitajima N, 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.
Takahashi K, Kitajima N, Abe N, Mishiro S. Complete or near-complete nucleotide sequences of hepatitis E virus genome recovered from a wild boar, a deer, and four patients who ate the deer. Virology. 2004;330:501–5.
Koizumi Y, Isoda N, Sato Y, et al. Infection of a Japanese patient by genotype 4 hepatitis e virus while traveling in Vietnam. J Clin Microbiol. 2004;42:3883–5.
Cacopardo B, Russo R, Preiser W, Benanti F, Brancati G, Nunnari A. Acute hepatitis E in Catania (eastern Sicily) 1980–1994. The role of hepatitis E virus. Infection. 1997;25:313–6.
Kuno A, Ido K, Isoda N, et al. Sporadic acute hepatitis E of a 47-year-old man whose pet cat was positive for antibody to hepatitis E virus. Hepatol Res. 2003;26:237–42.
Renou C, Cadranel JF, Bourliere M, et al. Possible zoonotic transmission of hepatitis E from pet pig to its owner. Emerg Infect Dis. 2007;13:1094–6.
Khuroo MS, Kamili S, Khuroo MS. Clinical course and duration of viremia in vertically transmitted hepatitis E virus (HEV) infection in babies born to HEV-infected mothers. J Viral Hepat. 2009;16:519–23.
Singh S, Mohanty A, Joshi YK, Deka D, Mohanty S, Panda SK. Mother-to-child transmission of hepatitis E virus infection. Indian J Pediatr. 2003;70:37–9.
Aggarwal R. Clinical presentation of hepatitis E. Virus Res. 2011;161:15–22.
Chibber RM, Usmani MA, Al-Sibai MH. Should HEV infected mothers breast feed? Arch Gynecol Obstet. 2004;270:15–20.
Guo H, Zhou EM, Sun ZF, Meng XJ. Egg whites from eggs of chickens infected experimentally with avian hepatitis E virus contain infectious virus, but evidence of complete vertical transmission is lacking. J Gen Virol. 2007;88:1532–7.
Kasorndorkbua C, Thacker BJ, Halbur PG, et al. Experimental infection of pregnant gilts with swine hepatitis E virus. Can J Vet Res. 2003;67:303–6.
Tsarev SA, Tsareva TS, Emerson SU, et al. Experimental hepatitis E in pregnant rhesus monkeys: failure to transmit hepatitis E virus (HEV) to offspring and evidence of naturally acquired antibodies to HEV. J Infect Dis. 1995;172:31–7.
Bajpai M, Gupta E. Transfusion-transmitted hepatitis E: is screening warranted? Indian J Med Microbiol. 2011;29:353–8.
Matsubayashi K, Kang JH, Sakata H, et al. A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route. Transfusion. 2008;48:1368–75.
Boxall E, Herborn A, Kochethu G, et al. Transfusion-transmitted hepatitis E in a ‘nonhyperendemic’ country. Transfus Med. 2006;16:79–83.
Mitsui T, Tsukamoto Y, Yamazaki C, et al. Prevalence of hepatitis E virus infection among hemodialysis patients in Japan: evidence for infection with a genotype 3 HEV by blood transfusion. J Med Virol. 2004;74:563–72.
Arankalle VA, Chobe LP. Retrospective analysis of blood transfusion recipients: evidence for post-transfusion hepatitis E. Vox Sang. 2000;79:72–4.
Tamura A, Shimizu YK, Tanaka T, et al. Persistent infection of hepatitis E virus transmitted by blood transfusion in a patient with T-cell lymphoma. Hepatol Res. 2007;37:113–20.
Fukuda S, Sunaga J, Saito N, et al. Prevalence of antibodies to hepatitis E virus among Japanese blood donors: identification of three blood donors infected with a genotype 3 hepatitis E virus. J Med Virol. 2004;73:554–61.
Adlhoch C, Kaiser M, Pauli G, Koch J, Meisel H. Indigenous hepatitis E virus infection of a plasma donor in Germany. Vox Sang. 2009;97:303–8.
Sakata H, Matsubayashi K, Takeda H, et al. A nationwide survey for hepatitis E virus prevalence in Japanese blood donors with elevated alanine aminotransferase. Transfusion. 2008;48:2568–76.
Chauhan A, Jameel S, Dilawari JB, Chawla YK, Kaur U, Ganguly NK. Hepatitis E virus transmission to a volunteer. Lancet. 1993;341:149–50.
Billam P, Huang FF, Sun ZF, et al. Systematic pathogenesis and replication of avian hepatitis E virus in specific-pathogen-free adult chickens. J Virol. 2005;79:3429–37.
Tsarev SA, Tsareva TS, Emerson SU, et al. Successful passive and active immunization of cynomolgus monkeys against hepatitis E. Proc Natl Acad Sci U S A. 1994;91:10198–202.
Jimenez de Oya N, Alonso-Padilla J, Blazquez AB, Escribano-Romero E, Escribano JM, Saiz JC. Maternal transfer of antibodies to the offspring after mice immunization with insect larvae-derived recombinant hepatitis E virus ORF-2 proteins. Virus Res. 2011;158:28–32.
Shata MT, Barrett A, Shire NJ, et al. Characterization of hepatitis E-specific cell-mediated immune response using IFN-gamma ELISPOT assay. J Immunol Methods. 2007;328:152–61.
Kamar N, Mansuy JM, Cointault O, et al. Hepatitis E virus-related cirrhosis in kidney- and kidney-pancreas-transplant recipients. Am J Transplant. 2008;8:1744–8.
Haagsma EB, van den Berg AP, Porte RJ, et al. Chronic hepatitis E virus infection in liver transplant recipients. Liver Transpl. 2008;14:547–53.
le Coutre P, Meisel H, Hofmann J, et al. Reactivation of hepatitis E infection in a patient with acute lymphoblastic leukaemia after allogeneic stem cell transplantation. Gut. 2009;58:699–702.
Kamar N, Rostaing L, Abravanel F, et al. Ribavirin therapy inhibits viral replication on patients with chronic hepatitis e virus infection. Gastroenterology. 2010;139:1612–8.
Kamar N, Selves J, Mansuy JM, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med. 2008;358:811–7.
Kamar N, Weclawiak H, Guilbeau-Frugier C, et al. Hepatitis E virus and the kidney in solid-organ transplant patients. Transplantation. 2012;93:617–23.
Schlosser B, Stein A, Neuhaus R, et al. Liver transplant from a donor with occult HEV infection induced chronic hepatitis and cirrhosis in the recipient. J Hepatol. 2012;56:500–2.
Chaillon A, Sirinelli A, De Muret A, Nicand E, d’Alteroche L, Goudeau A. Sustained virologic response with ribavirin in chronic hepatitis E virus infection in heart transplantation. J Heart Lung Transplant. 2011;30:841–3.
Dalton HR, Bendall RP, Keane FE, Tedder RS, Ijaz S. Persistent carriage of hepatitis E virus in patients with HIV infection. N Engl J Med. 2009;361:1025–7.
Dalton HR, Keane FE, Bendall R, Mathew J, Ijaz S. Treatment of chronic hepatitis E in a patient with HIV infection. Ann Intern Med. 2011;155:479–80.
Jagjit Singh GK, Ijaz S, Rockwood N, et al. Chronic Hepatitis E as a cause for cryptogenic cirrhosis in HIV. J Infect. 2013;66:103–6.
Kenfak-Foguena A, Schoni-Affolter F, Burgisser P, et al. Hepatitis E Virus seroprevalence and chronic infections in patients with HIV, Switzerland. Emerg Infect Dis. 2011;17:1074–8.
Sanford BJ, Dryman BA, Huang YW, Feagins AR, Leroith T, Meng XJ. Prior infection of pigs with a genotype 3 swine hepatitis E virus (HEV) protects against subsequent challenges with homologous and heterologous genotypes 3 and 4 human HEV. Virus Res. 2011;159:17–22.
Kamar N, Bendall RP, Peron JM, et al. Hepatitis E virus and neurologic disorders. Emerg Infect Dis. 2011;17:173–9.
Kamar N, Izopet J, Cintas P, et al. Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis. Am J Transplant. 2010;10:1321–4.
Despierres LA, Kaphan E, Attarian S, et al. Neurologic disorders and hepatitis E, France, 2010. Emerg Infect Dis. 2011;17:1510–2.
Cronin S, McNicholas R, Kavanagh E, Reid V, O’Rourke K. Anti-glycolipid GM2-positive Guillain-Barre syndrome due to hepatitis E infection. Ir J Med Sci. 2011;180:255–7.
Tse AC, Cheung RT, Ho SL, Chan KH. Guillain-Barre syndrome associated with acute hepatitis E infection. J Clin Neurosci. 2012;19:607–8.
Meng XJ. Swine hepatitis E virus: cross-species infection and risk in xenotransplantation. Curr Top Microbiol Immunol. 2003;278:185–216.
Kamar N, Abravanel F, Garrouste C, et al. Three-month pegylated interferon-alpha-2a therapy for chronic hepatitis E virus infection in a haemodialysis patient. Nephrol Dial Transplant. 2010;25:2792–5.
Mallet V, Nicand E, Sultanik P, et al. Brief communication: case reports of ribavirin treatment for chronic hepatitis E. Ann Intern Med. 2010;153:85–9.
Gerolami R, Borentain P, Raissouni F, Motte A, Solas C, Colson P. Treatment of severe acute hepatitis E by ribavirin. J Clin Virol. 2011;52:60–2.
Dong C, Zafrullah M, Mixson-Hayden T, et al. Suppression of interferon-alpha signaling by hepatitis E virus. Hepatology. 2012;55:1324–32.
Kumar A, Panda SK, Durgapal H, Acharya SK, Rehman S, Kar UK. Inhibition of Hepatitis E virus replication using short hairpin RNA (shRNA). Antiviral Res. 2010;85:541–50.
Huang F, Hua X, Yang S, Yuan C, Zhang W. Effective inhibition of hepatitis E virus replication in A549 cells and piglets by RNA interference (RNAi) targeting RNA-dependent RNA polymerase. Antiviral Res. 2009;83:274–81.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this chapter
Cite this chapter
Meng, XJ. (2014). Hepatitis E Virus. In: Kaslow, R., Stanberry, L., Le Duc, J. (eds) Viral Infections of Humans. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7448-8_18
Download citation
DOI: https://doi.org/10.1007/978-1-4899-7448-8_18
Published:
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4899-7447-1
Online ISBN: 978-1-4899-7448-8
eBook Packages: MedicineMedicine (R0)