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Correspondence

Chronic Hepatitis E with Cirrhosis in a Kidney-Transplant Recipient

N Engl J Med 2008; 358:859-860February 21, 2008

Article

To the Editor:

Hepatitis E virus (HEV) is an important cause of acute viral hepatitis worldwide.1 Kamar et al. in this issue of the Journal 2 and others3,4 have recently suggested that HEV infection might result in chronic hepatitis in immunocompromised patients. We report a rapidly progressing case of cirrhosis in a renal-transplant recipient with chronic HEV infection.

A 52-year-old man who had undergone kidney transplantation in March 2005 presented with increased aminotransferase levels in June 2006. Four months later, the alanine aminotransferase level reached 126 U per liter and thereafter plateaued at three times the upper limit of the normal range. Serologic testing for hepatitis C virus (HCV) and HCV RNA had been negative at the time of transplantation and during follow-up. The results of serologic testing for hepatitis B virus (HBV) were consistent with past immunization, and HBV DNA was undetectable. The patient's alcohol consumption was lower than 10 g per day. Other causes of chronic hepatitis were ruled out.

Hepatitis E was diagnosed in June 2007 on the basis of positive results on IgM anti-HEV antibody testing (EIAGen kit, Adaltis) and HEV RNA detection (genotype 3f; GenBank accession number, EU116340).5 The patient did not report any recent travel, and no potential route of HEV transmission other than consumption of pork was identified. Retrospective analysis showed that HEV RNA was undetectable in the patient's serum in April 2006, whereas it was repeatedly detected in available serum samples from November 2006 to September 2007 (Figure 1AFigure 1Results of Virologic Analysis and Liver Biopsy in a Patient with Chronic Hepatitis E Virus Infection.), when the diagnosis of active chronic hepatitis and cirrhosis was confirmed on liver biopsy (Figure 1B and 1C).

HEV-related cirrhosis appears to be a novel observation. Other unusual features in this patient were a low peak alanine aminotransferase level (no higher than 126 U per liter) and the absence of IgG anti-HEV antibody seroconversion. The unusual course might be explained to a great extent by the patient's immunosuppressed state. A few cases of protracted HEV infection and even HEV-related chronic active hepatitis have recently been described in patients who received solid-organ transplants.2-4 Our observation further suggests that chronic HEV infection may induce rapid and severe liver disease.

Persistently negative results of IgG anti-HEV antibody testing have previously been observed in the context of immunosuppression, despite evidence of HEV infection, as assessed by HEV RNA detection in blood.6 The present case highlights the need to diagnose HEV infection on the basis of molecular testing rather than only serologic assays in such settings.

In conclusion, this case indicates that HEV infection may result in active chronic hepatitis and rapid progression to cirrhosis in organ-transplant recipients. Further studies are needed to assess the actual incidence, prevalence, and clinical effect of autochthonous HEV infection in these patients.

René Gérolami, M.D., Ph.D.
Valérie Moal, M.D.
Centre Hospitalier Universitaire Conception, 13385 Marseille, France

Philippe Colson, Pharm.D., Ph.D.
Centre Hospitalier Universitaire Timone, 13385 Marseille, France

6 References
  1. 1

    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
    Full Text | Web of Science | Medline

  2. 2

    Kamar N, Selves J, Mansuy J-M, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 2008;358:811-819
    Full Text | Web of Science | Medline

  3. 3

    Banas B, Tausch U, Hofstadter F, et al. Infection with hepatitis E virus: first report of a chronic case and molecular characterization of the virus. J Clin Virol 2006;36:Suppl 2:S162-S162
    CrossRef | Web of Science

  4. 4

    Kamar N, Peron JM, Ouezzani L, et al. Hepatitis E virus infection can evolve to chronic hepatitis in organ-transplant patients. J Hepatol 2007;46:Suppl 1:S70-S71
    CrossRef | Web of Science

  5. 5

    Colson P, Borentain P, Motte A, et al. First human cases of hepatitis E infection with genotype 3c strains. J Clin Virol 2007;40:318-320
    CrossRef | Web of Science | Medline

  6. 6

    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;37:113-120
    CrossRef | Web of Science | Medline

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  1. 1

    Florence Abravanel, Jean-Michel Mansuy, Anne Huynh, Nassim Kamar, Laurent Alric, Jean-Marie Peron, Christian Récher, Jacques Izopet. (2012) Low risk of hepatitis E virus reactivation after haematopoietic stem cell transplantation. Journal of Clinical Virology 54:2, 152-155
    CrossRef

  2. 2

    Heiner Wedemeyer, Sven Pischke, Michael P. Manns. (2012) Pathogenesis and Treatment of Hepatitis E Virus Infection. Gastroenterology 142:6, 1388-1397.e1
    CrossRef

  3. 3

    Nassim Kamar, Richard Bendall, Florence Legrand-Abravanel, Ning-Shao Xia, Samreen Ijaz, Jacques Izopet, Harry R Dalton. (2012) Hepatitis E. The Lancet
    CrossRef

  4. 4

    N. Kamar, F. Legrand-Abravanel, J. Izopet, L. Rostaing. (2012) Hepatitis E Virus: What Transplant Physicians Should Know. American Journal of Transplantationno-no
    CrossRef

  5. 5

    V. Yiu, R. Gao, S. Mulroy. (2012) Hepatitis in a renal transplant patient--beyond the usual. Clinical Kidney Journal
    CrossRef

  6. 6

    Francisco Rodríguez-Frias, Rosendo Jardi, María Buti. (2012) Hepatitis E: virología molecular, epidemiología y patogénesis. Enfermedades Infecciosas y Microbiología Clínica
    CrossRef

  7. 7

    Anne Motte, Bertrand Roquelaure, Claire Galambrun, Fanette Bernard, Christine Zandotti, Philippe Colson. (2012) Hepatitis E in three immunocompromized children in southeastern France. Journal of Clinical Virology 53:2, 162-166
    CrossRef

  8. 8

    Stefan G. Hübscher, Andrew D. Clouston. 2012. Transplantation pathology. , 853-933.
    CrossRef

  9. 9

    Itaru Ozeki, Jong-Hon Kang, Hitoshi Mizuo, Jun Akaike, Takumi Ohmura, Yoshiyasu Karino, Takeshi Matsui, Akiyoshi Saga, Masao Watanabe, Yohsuke Miura, Toshiroh Kura, Izumi Tsunematsu, Keiji Matsubayashi, Hidekatsu Sakata, Hiroaki Okamoto, Kazuaki Takahashi, Masahiro Arai. (2012) Small epidemic of hepatitis E in the fall 2009 in Sapporo, Hokkaido. Kanzo 53:2, 78-89
    CrossRef

  10. 10

    Koji Ogawa, Yoshiya Yamamoto, Machiko Umemura, Jong-Hon Kang, Hidekatsu Sakata, Keiji Matsubayashi, Kazuaki Takahashi, Masahiro Arai, Shunji Mishiro. (2012) Two cases of fulminant hepatitis E occurred in Hakodate area 2010, suggesting infection with single source hepatitis E virus separated from small epidemic in Sapporo 2009. Kanzo 53:4, 206-215
    CrossRef

  11. 11

    Joshua Watson, Maria H. Sjogren. 2011. Hepatitis A and E. , 521-536.
    CrossRef

  12. 12

    Gurmit K. Jagjit Singh, Samreen Ijaz, Neesha Rockwood, Simon P. Farnworth, Emma Devitt, Mark Atkins, Richard Tedder, Mark Nelson. (2011) Chronic Hepatitis E as a cause for cryptogenic cirrhosis in HIV. Journal of Infection
    CrossRef

  13. 13

    Irene Cacciola, Federica Messineo, Bruno Cacopardo, Vito Di Marco, Claudio Galli, Giovanni Squadrito, Cristina Musolino, Carlo Saitta, Teresa Pollicino, Giovanni Raimondo. (2011) Hepatitis E virus infection as a cause of acute hepatitis in Southern Italy. Digestive and Liver Disease 43:12, 996-1000
    CrossRef

  14. 14

    Rakesh Aggarwal, Shahid Jameel. (2011) Hepatitis E. Hepatology 54:6, 2218-2226
    CrossRef

  15. 15

    Rakesh Aggarwal. (2011) Clinical presentation of hepatitis E. Virus Research 161:1, 15-22
    CrossRef

  16. 16

    Tatsuo Miyamura. (2011) Hepatitis E virus infection in developed countries. Virus Research 161:1, 40-46
    CrossRef

  17. 17

    Mamadou Kaba, Hervé Richet, Isabelle Ravaux, Jacques Moreau, Isabelle Poizot-Martin, Anne Motte, Corinne Nicolino-Brunet, Françoise Dignat-George, Amélie Ménard, Catherine Dhiver, Philippe Brouqui, Philippe Colson. (2011) Hepatitis E virus infection in patients infected with the human immunodeficiency virus. Journal of Medical Virology 83:10, 1704-1716
    CrossRef

  18. 18

    Jürgen J. Wenzel, Julia Preiß, Mathias Schemmerer, Barbara Huber, Annelie Plentz, Wolfgang Jilg. (2011) Detection of hepatitis E virus (HEV) from porcine livers in Southeastern Germany and high sequence homology to human HEV isolates. Journal of Clinical Virology 52:1, 50-54
    CrossRef

  19. 19

    Nicolas Rose, Aurélie Lunazzi, Virginie Dorenlor, Thiziri Merbah, Florent Eono, Marc Eloit, François Madec, Nicole Pavio. (2011) High prevalence of Hepatitis E virus in French domestic pigs. Comparative Immunology, Microbiology and Infectious Diseases 34:5, 419-427
    CrossRef

  20. 20

    D. Halleux, N. Kanaan, B. Kabamba, I. Thomas, Z. Hassoun. (2011) Hepatitis E virus: an underdiagnosed cause of chronic hepatitis in renal transplant recipients. Transplant Infectious Diseasen/a-n/a
    CrossRef

  21. 21

    Anais Vallet-Pichard, Hélène Fontaine, Vincent Mallet, Stanislas Pol. (2011) VIRAL hepatitis in solid organ transplantation other than liver. Journal of Hepatology 55:2, 474-482
    CrossRef

  22. 22

    Ana Isabel González Tallón, Víctor Moreira Vicente, María Luisa Mateos Lindemann, Linette María Achécar Justo. (2011) Hepatitis crónica E en paciente inmunocompetente. Gastroenterología y Hepatología 34:6, 398-400
    CrossRef

  23. 23

    Joseph Torresi, Douglas Johnson. (2011) Hepatitis A and E Infection in International Travellers. Current Infectious Disease Reports 13:3, 248-255
    CrossRef

  24. 24

    Nassim Kamar, Cyril Garrouste, Elizabeth B. Haagsma, Valérie Garrigue, Sven Pischke, Cécile Chauvet, Jérome Dumortier, Amélie Cannesson, Elisabeth Cassuto–Viguier, Eric Thervet, Filomena Conti, Pascal Lebray, Harry R. Dalton, Robert Santella, Nada Kanaan, Marie Essig, Christiane Mousson, Sylvie Radenne, Anne Marie Roque–Afonso, Jacques Izopet, Lionel Rostaing. (2011) Factors Associated With Chronic Hepatitis in Patients With Hepatitis E Virus Infection Who Have Received Solid Organ Transplants. Gastroenterology 140:5, 1481-1489
    CrossRef

  25. 25

    Ana Isabel González Tallón, Víctor Moreira Vicente, María Luisa Mateos Lindemann. (2011) Hepatitis crónica E. Medicina Clínica
    CrossRef

  26. 26

    F. WIDÉN, L. SUNDQVIST, A. MATYI-TOTH, G. METREVELI, S. BELÁK, G. HALLGREN, H. NORDER. (2011) Molecular epidemiology of hepatitis E virus in humans, pigs and wild boars in Sweden. Epidemiology and Infection 139:03, 361-371
    CrossRef

  27. 27

    Rakesh Aggarwal. (2011) Hepatitis E: Historical, contemporary and future perspectives. Journal of Gastroenterology and Hepatology 26, 72-82
    CrossRef

  28. 28

    David B. Rein, Gretchen Stevens, Jordan Theaker, John S. Wittenborn, Steven T. Wiersma. (2011) The global burden of hepatitis E virus. Hepatologyn/a-n/a
    CrossRef

  29. 29

    Luisa Romanò, Sara Paladini, Catia Tagliacarne, Marta Canuti, Silvia Bianchi, Alessandro Remo Zanetti. (2011) Hepatitis E in Italy: A long-term prospective study. Journal of Hepatology 54:1, 34-40
    CrossRef

  30. 30

    Hui-Hui Tan, Hoe-Nam Leong, Boon-Huan Tan, Lynette Lin-Ean Oon, Kiat-Hon Lim, Jason Pik-Eu Chang, Chee-Kiat Tan. (2011) Chronic Hepatitis E Infection Resulting in Graft Failure in a Liver Transplant Tourist. Case Reports in Transplantation 2011, 1-6
    CrossRef

  31. 31

    Janick Selves, Nassim Kamar, Jean-Michel Mansuy, Jean-Marie Péron. (2010) Les hépatites virales E : une maladie émergente en France. Annales de Pathologie 30:6, 432-438
    CrossRef

  32. 32

    Nassim Kamar, Lionel Rostaing, Florence Abravanel, Cyril Garrouste, Sebastien Lhomme, Laure Esposito, Grégoire Basse, Olivier Cointault, David Ribes, Marie Béatrice Nogier, Laurent Alric, Jean Marie Peron, Jacques Izopet. (2010) Ribavirin Therapy Inhibits Viral Replication on Patients With Chronic Hepatitis E Virus Infection. Gastroenterology 139:5, 1612-1618
    CrossRef

  33. 33

    Nicole Pavio, Jean-Michel Mansuy. (2010) Hepatitis E in high-income countries. Current Opinion in Infectious Diseases 23:5, 521-527
    CrossRef

  34. 34

    Juan F. Gallegos-Orozco, Jorge Rakela. 2010. Acute Viral Hepatitis: Hepatitis A, Hepatitis E, and Other Viruses. , 173-185.
    CrossRef

  35. 35

    N. Kamar, F. Abravanel, C. Garrouste, I. Cardeau-Desangles, J. M. Mansuy, H. Weclawiak, J. Izopet, L. Rostaing. (2010) Three-month pegylated interferon-alpha-2a therapy for chronic hepatitis E virus infection in a haemodialysis patient. Nephrology Dialysis Transplantation 25:8, 2792-2795
    CrossRef

  36. 36

    Christophe Renou, Alain Lafeuillade, Jean-François Cadranel, Nicole Pavio, Alexandre Pariente, Thierry Allègre, Cécile Poggi, Guillaume Pénaranda, François Cordier, Elisabeth Nicand. (2010) Hepatitis E virus in HIV-infected patients. AIDS 24:10, 1493-1499
    CrossRef

  37. 37

    F. Bihl, F. Negro. (2010) Hepatitis E virus: a zoonosis adapting to humans. Journal of Antimicrobial Chemotherapy 65:5, 817-821
    CrossRef

  38. 38

    Philippe Colson, René Gérolami, Jacques Moreau, Patrick Borentain, Philippe Brouqui. (2010) Concurrent autochthonous acute hepatitis E and hepatitis B reverse seroconversion in an HIV-1-infected patient: one virus may hide another. International Journal of Infectious Diseases 14:4, e357
    CrossRef

  39. 39

    Nassim Kamar, Florence Abravanel, Janick Selves, Cyril Garrouste, Laure Esposito, Laurence Lavayssière, Olivier Cointault, David Ribes, Isabelle Cardeau, Marie Béatrice Nogier, Jean Michel Mansuy, Fabrice Muscari, Jean Marie Peron, Jacques Izopet, Lionel Rostaing. (2010) Influence of Immunosuppressive Therapy on the Natural History of Genotype 3 Hepatitis-E Virus Infection After Organ Transplantation. Transplantation 89:3, 353-360
    CrossRef

  40. 40

    H. C. LEWIS, O. WICHMANN, E. DUIZER. (2010) Transmission routes and risk factors for autochthonous hepatitis E virus infection in Europe: a systematic review. Epidemiology and Infection 138:02, 145
    CrossRef

  41. 41

    Maria Buti, Cecilia Cabrera, Rosendo Jardi, Luis Castells, Rafael Esteban. (2010) Are recipients of solid organ transplantation a high-risk population for hepatitis E virus infection?. Liver Transplantation 16:1, 106-107
    CrossRef

  42. 42

    Sven Pischke, Pothakamuri V. Suneetha, Christine Baechlein, Hannelore Barg-Hock, Albert Heim, Nassim Kamar, Jerome Schlue, Christian P. Strassburg, Frank Lehner, Regina Raupach, Birgit Bremer, Peter Magerstedt, Markus Cornberg, Frauke Seehusen, Wolfgang Baumgaertner, Juergen Klempnauer, Jacques Izopet, Michael P. Manns, B. Grummer, Heiner Wedemeyer. (2010) Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients. Liver Transplantation 16:1, 74-82
    CrossRef

  43. 43

    Emmanuel Wey, Chris Kibbler. 2010. Infections associated with neutropenia and transplantation. , 502-523.
    CrossRef

  44. 44

    Rakesh Aggarwal, Krzysztof Krawczynski. 2010. Hepatitis E. , 1337-1342.
    CrossRef

  45. 45

    Mariana Ghinoiu, Sylvie Naveau, Nadège Barri-Ova, Juliette Thaury, Liliane Grangeot-Keros, Gabriel Perlemuter. (2009) Acute hepatitis E infection associated with a false-positive serology against Epstein–Barr virus. European Journal of Gastroenterology & Hepatology 21:12, 1433-1435
    CrossRef

  46. 46

    M. Fogeda, A. Avellón, C.G. Cilla, J.M. Echevarría. (2009) Imported and autochthonous hepatitis E virus strains in Spain. Journal of Medical Virology 81:10, 1743-1749
    CrossRef

  47. 47

    Mamadou Kaba, Bernard Davoust, Jean-Lou Marié, Marc Barthet, Mireille Henry, Catherine Tamalet, Didier Raoult, Philippe Colson. (2009) Frequent transmission of hepatitis E virus among piglets in farms in Southern France. Journal of Medical Virology 81:10, 1750-1759
    CrossRef

  48. 48

    Elizabeth B. Haagsma, Hubert G. M. Niesters, Arie P. van den Berg, Annelies Riezebos-Brilman, Robert J. Porte, Harry Vennema, Johan H. J. Reimerink, Marion P. G. Koopmans. (2009) Prevalence of hepatitis E virus infection in liver transplant recipients. Liver Transplantation 15:10, 1225-1228
    CrossRef

  49. 49

    Rakesh Aggarwal, Sita Naik. (2009) Epidemiology of hepatitis E: Current status. Journal of Gastroenterology and Hepatology 24:9, 1484-1493
    CrossRef

  50. 50

    Philippe Colson, Mamadou Kaba, Jacques Moreau, Philippe Brouqui. (2009) Hepatitis E in an HIV-infected patient. Journal of Clinical Virology 45:4, 269-271
    CrossRef

  51. 51

    Linda Scobie, Yasuhiro Takeuchi. (2009) Porcine endogenous retrovirus and other viruses in xenotransplantation. Current Opinion in Organ Transplantation 14:2, 175-179
    CrossRef

  52. 52

    Jay H. Lefkowitch. (2009) Recent developments in liver pathology. Human Pathology 40:4, 445-455
    CrossRef

  53. 53

    René Gérolami, Valérie Moal, Christophe Picard, Philippe Colson. (2009) Hepatitis E virus as an emerging cause of chronic liver disease in organ transplant recipients. Journal of Hepatology 50:3, 622-624
    CrossRef

  54. 54

    Florian Bihl, Francesco Negro. (2009) Chronic hepatitis E in the immunosuppressed: A new source of trouble?. Journal of Hepatology 50:2, 435-437
    CrossRef

  55. 55

    P. Colson, C. Dhiver, R. Gérolami. (2008) Hepatitis E virus as a newly identified cause of acute viral hepatitis during human immunodeficiency virus infection. Clinical Microbiology and Infection 14:12, 1176-1180
    CrossRef

  56. 56

    Mohammad S Khuroo, Mehnaaz S Khuroo. (2008) Hepatitis E virus. Current Opinion in Infectious Diseases 21:5, 539-543
    CrossRef

  57. 57

    Rakesh Aggarwal, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein. (2008) Hepatitis E: Does it cause chronic hepatitis?. Hepatology 48:4, 1328-1330
    CrossRef

  58. 58

    N. Kamar, J.-M. Mansuy, O. Cointault, J. Selves, F. Abravanel, M. Danjoux, P. Otal, L. Esposito, D. Durand, J. Izopet, L. Rostaing. (2008) Hepatitis E Virus-Related Cirrhosis in Kidney-and Kidney-Pancreas-Transplant Recipients. American Journal of Transplantation 8:8, 1744-1748
    CrossRef

  59. 59

    (2008) Chronic Hepatitis E and Organ Transplants. New England Journal of Medicine 358:23, 2521-2522
    Full Text

  60. 60

    Tai-Nin Chau. (2008) Hepatitis E: A potential vaccine-preventable disease needs global concern. Journal of Gastroenterology and Hepatology 23:6, 827-828
    CrossRef