Correspondence

Chronic Hepatitis E and Organ Transplants

N Engl J Med 2008; 358:2521-2522June 5, 2008

Article

To the Editor:

Kamar and colleagues (Feb. 21 issue)1 report eight cases of chronic hepatitis E virus (HEV) infection in immunosuppressed organ-transplant recipients, a constellation that was hitherto not observed. One wonders whether the persistence of HEV infection is a more general consequence of immunosuppression, which has implications for all so-called nonpersistent pathogens. Previously, we observed prolonged and possibly chronic shedding of human metapneumovirus in two patients with cancer who were immunosuppressed because they were receiving chemotherapy.2 Furthermore, it was recently reported that immunosuppression induced by lactate dehydrogenase–elevating virus led to increases in the severity and duration of the acute phase of friend virus infection in mice, most likely because of diminished CD8− responses.3 Such observations may provide support for earlier assumptions that if the CD4+ defense is insufficient because of immunosuppression, the CD8− response is unlikely to eliminate infection.4 The study by Kamar et al. revealed significantly reduced CD4− counts in patients with chronic HEV infection. Under these specific circumstances, so-called nonpersistent viruses may cause chronic colonization and recurrent infection. Hence, reducing drug-induced immunosuppression during acute HEV infection might be a strategy to prevent the progression to chronic hepatitis.

Oliver Schildgen, Ph.D.
Andreas Müller, M.D.
Arne Simon, M.D.
University of Bonn, 53105 Bonn, Germany
schildgen@virology-bonn.de

4 References

1. 1

   Kamar N, Selves J, Mansuy J-M, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med 2008;358:811-817
   Full Text | Web of Science | Medline

2. 2

   Wilkesmann A, Schildgen O, Eis-Hubinger AM, et al. Human metapneumovirus infections cause similar symptoms and clinical severity as respiratory syncytial virus infections. Eur J Pediatr 2006;165:467-475
   CrossRef | Web of Science | Medline

3. 3

   Robertson SJ, Ammann CG, Messer RJ, et al. Suppression of acute anti-friend virus CD8+ T-cell responses by coinfection with lactate dehydrogenase-elevating virus. J Virol 2008;82:408-418
   CrossRef | Web of Science | Medline

4. 4

   Wherry EJ, Ha SJ, Kaech SM, et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 2007;27:670-684[Erratum, Immunity 2007;27:824.]
   CrossRef | Web of Science | Medline

Author/Editor Response

With regard to the comments by Schildgen et al., prolonged acute hepatitis A virus and HEV infections have been reported previously in both immunocompromised and nonimmunocompromised patients.1,2 Our report indicated that HEV infection may evolve to chronic hepatitis in organ-transplant recipients. In addition, a unique case of HEV-related cirrhosis has recently been reported.3 Schildgen et al. suggest that the evolution of HEV infection to chronic hepatitis is related to marked immunosuppression. They base their assumption on two studies of viral infections that appear to be unrelated to those that have been observed in organ-transplant recipients. We agree that the evolution of HEV infection to chronic hepatitis in the setting of marked immunosuppression may be a mechanism, since we have found a lower CD4+ cell count in patients in whom chronic hepatitis evolved than in patients who were clear of the virus. Hence, in HEV-infected transplant recipients, we suggest reducing immunosuppressive therapies that target T cells (i.e., mainly calcineurin inhibitors) in order to allow clearance of the virus.

Nassim Kamar, M.D., Ph.D.
Jacques Izopet, Pharm.D., Ph.D.
Lionel Rostaing, M.D., Ph.D.
Toulouse University Hospital, 31059 Toulouse, France
kamar.n@chu-toulouse.fr

3 References

1. 1

   Costa-Mattioli M, Allavena C, Poirier AS, Billaudel S, Raffi F, Ferre V. Prolonged hepatitis A infection in an HIV-1 seropositive patient. J Med Virol 2002;68:7-11
   CrossRef | Web of Science | Medline

2. 2

   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

3. 3

   Gerolami R, Moal V, Colson P. Chronic hepatitis E with cirrhosis in a kidney-transplant recipient. N Engl J Med 2008;358:859-860
   Full Text | Web of Science | Medline

Citing Articles (4)

Citing Articles

1. 1

   S.K. Sarin, Manoj Kumar. 2012. Hepatitis E. , 605-628.
   CrossRef

2. 2

   M. S. Khuroo, S. Kamili, M. S. Khuroo. (2009) Clinical course and duration of viremia in vertically transmitted hepatitis E virus (HEV) infection in babies born to HEV-infected mothers. Journal of Viral Hepatitis 16:7, 519-523
   CrossRef

3. 3

   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

4. 4

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