Rat Hepatitis E Virus As Cause of Persistent Hepatitis After Liver Transplant

Overview

Journal Emerg Infect Dis

Specialty Infectious Diseases

Date 2018 Nov 21

PMID 30457530

Citations 101

Authors

Siddharth Sridhar

Cyril C Y Yip

Shusheng Wu

Jianpiao Cai

Anna Jin-Xia Zhang

Kit-Hang Leung

Tom W H Chung

Jasper F W Chan

Wan-Mui Chan

Jade L L Teng

Rex K H Au-Yeung

Vincent C C Cheng

Honglin Chen

Susanna K P Lau

Patrick C Y Woo

Ning-Shao Xia

Chung-Mau Lo

Kwok-Yung Yuen

Affiliations

Soon will be listed here.

Abstract

All hepatitis E virus (HEV) variants reported to infect humans belong to the species Orthohepevirus A (HEV-A). The zoonotic potential of the species Orthohepevirus C (HEV-C), which circulates in rats and is highly divergent from HEV-A, is unknown. We report a liver transplant recipient with hepatitis caused by HEV-C infection. We detected HEV-C RNA in multiple clinical samples and HEV-C antigen in the liver. The complete genome of the HEV-C isolate had 93.7% nt similarity to an HEV-C strain from Vietnam. The patient had preexisting HEV antibodies, which were not protective against HEV-C infection. Ribavirin was an effective treatment, resulting in resolution of hepatitis and clearance of HEV-C viremia. Testing for this zoonotic virus should be performed for immunocompromised and immunocompetent patients with unexplained hepatitis because routine hepatitis E diagnostic tests may miss HEV-C infection. HEV-C is also a potential threat to the blood product supply.

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References

Purcell R, Engle R, Rood M, Kabrane-Lazizi Y, Nguyen H, Govindarajan S . Hepatitis E virus in rats, Los Angeles, California, USA. Emerg Infect Dis. 2011; 17(12):2216-22. PMC: 3311208. DOI: 10.3201/eid1712.110482. View

Sanford B, Opriessnig T, Kenney S, Dryman B, Cordoba L, Meng X . Assessment of the cross-protective capability of recombinant capsid proteins derived from pig, rat, and avian hepatitis E viruses (HEV) against challenge with a genotype 3 HEV in pigs. Vaccine. 2012; 30(44):6249-55. PMC: 3446255. DOI: 10.1016/j.vaccine.2012.08.013. View

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(Pt 3):903-911. DOI: 10.1099/vir.0.82535-0. View

Dremsek P, Wenzel J, Johne R, Ziller M, Hofmann J, Groschup M . Seroprevalence study in forestry workers from eastern Germany using novel genotype 3- and rat hepatitis E virus-specific immunoglobulin G ELISAs. Med Microbiol Immunol. 2011; 201(2):189-200. DOI: 10.1007/s00430-011-0221-2. View

Ding Q, Heller B, Capuccino J, Song B, Nimgaonkar I, Hrebikova G . Hepatitis E virus ORF3 is a functional ion channel required for release of infectious particles. Proc Natl Acad Sci U S A. 2017; 114(5):1147-1152. PMC: 5293053. DOI: 10.1073/pnas.1614955114. View

Sridhar S, Lo S, Xing F, Yang J, Ye H, Chan J . Clinical characteristics and molecular epidemiology of hepatitis E in Shenzhen, China: a shift toward foodborne transmission of hepatitis E virus infection. Emerg Microbes Infect. 2017; 6(12):e115. PMC: 5750461. DOI: 10.1038/emi.2017.107. View

Emerson S, Nguyen H, Graff J, Stephany D, Brockington A, Purcell R . In vitro replication of hepatitis E virus (HEV) genomes and of an HEV replicon expressing green fluorescent protein. J Virol. 2004; 78(9):4838-46. PMC: 387676. DOI: 10.1128/jvi.78.9.4838-4846.2004. View

Colson P, Coze C, Gallian P, Henry M, de Micco P, Tamalet C . Transfusion-associated hepatitis E, France. Emerg Infect Dis. 2007; 13(4):648-9. PMC: 2725983. DOI: 10.3201/eid1304.061387. View

Chan J, Chan K, Choi G, To K, Tse H, Cai J . Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: implications for disease pathogenesis and clinical manifestation. J Infect Dis. 2013; 207(11):1743-52. PMC: 7107374. DOI: 10.1093/infdis/jit123. View

10.

Chan J, Yip C, Tsang J, Tee K, Cai J, Chik K . Differential cell line susceptibility to the emerging Zika virus: implications for disease pathogenesis, non-vector-borne human transmission and animal reservoirs. Emerg Microbes Infect. 2016; 5:e93. PMC: 5034105. DOI: 10.1038/emi.2016.99. View

11.

Hewitt P, Ijaz S, Brailsford S, Brett R, Dicks S, Haywood B . Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet. 2014; 384(9956):1766-73. DOI: 10.1016/S0140-6736(14)61034-5. View

12.

Tei S, Kitajima N, Takahashi K, Mishiro S . Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet. 2003; 362(9381):371-3. DOI: 10.1016/S0140-6736(03)14025-1. View

13.

Johne R, Plenge-Bonig A, Hess M, Ulrich R, 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. 2009; 91(Pt 3):750-8. DOI: 10.1099/vir.0.016584-0. View

14.

Lee G, Tan B, Teo E, Lim S, Dan Y, Wee A . Chronic Infection With Camelid Hepatitis E Virus in a Liver Transplant Recipient Who Regularly Consumes Camel Meat and Milk. Gastroenterology. 2015; 150(2):355-7.e3. DOI: 10.1053/j.gastro.2015.10.048. View

15.

Tamura K, Stecher G, Peterson D, Filipski A, Kumar S . MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013; 30(12):2725-9. PMC: 3840312. DOI: 10.1093/molbev/mst197. View

16.

Cheng V, Chan J, Wen X, Wu W, Que T, Chen H . Infection of immunocompromised patients by avian H9N2 influenza A virus. J Infect. 2011; 62(5):394-9. DOI: 10.1016/j.jinf.2011.02.007. View

17.

Mansuy J, Peron J, Abravanel F, Poirson H, Dubois M, Miedouge M . Hepatitis E in the south west of France in individuals who have never visited an endemic area. J Med Virol. 2004; 74(3):419-24. DOI: 10.1002/jmv.20206. View

18.

Zhang J, Li S, Wu T, Zhao Q, Ng M, Xia N . Hepatitis E virus: neutralizing sites, diagnosis, and protective immunity. Rev Med Virol. 2012; 22(5):339-49. DOI: 10.1002/rmv.1719. View

19.

Abravanel F, Lhomme S, El Costa H, Schvartz B, Peron J, Kamar N . Rabbit Hepatitis E Virus Infections in Humans, France. Emerg Infect Dis. 2017; 23(7):1191-1193. PMC: 5512490. DOI: 10.3201/eid2307.170318. View

20.

Rein D, Stevens G, Theaker J, Wittenborn J, Wiersma S . The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology. 2011; 55(4):988-97. DOI: 10.1002/hep.25505. View