Correspondence

Long-Term Outcome of Hepatitis C Infection after Liver Transplantation

N Engl J Med 1996; 335:522-523August 15, 1996

Article

To the Editor:

Gane et al. (March 28 issue)1 found that five years after liver transplantation, rates of graft and overall survival were similar between patients with and those without hepatitis C virus (HCV) infection. However, they also showed that after transplantation, persistent HCV infection can cause severe damage to the graft, and they suggest that with longer follow-up HCV-infected patients may have more problems than patients without HCV infection. We have made the same observation in HCV-infected patients who have undergone renal transplantation.

In our initial study, rates of graft and overall survival were similar between patients with antibody to HCV and those without it a mean of 51 months after transplantation.2 Others have reported similar findings.3,4 With a longer mean (±SD) follow-up (84±54 months), our results were less satisfactory. Among patients with kidney transplants, none of whom had hepatitis B–associated infection, 65 percent of 153 patients who had antibody to HCV survived at 100 months, as compared with 82 percent of 495 patients without HCV antibody (P<0.001); the rates of survival at 200 months were 41 percent and 67 percent, respectively (P<0.001). Similar differences were found with regard to allograft survival. Mortality among kidney-transplant recipients positive for HCV antibody was frequently related to liver diseases, such as cirrhosis and hepatocellular carcinoma.

Stanislas Pol, M.D., Ph.D.
Valérie Garrigue, M.D.
Christophe Legendre, M.D.
Hôpital Necker, 75747 Paris, France

4 References

1. 1

   Gane EJ, Portmann BC, Naoumov NV, et al. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med 1996;334:815-820
   Full Text | Web of Science | Medline

2. 2

   Pol S, Legendre C, Saltiel C, et al. Hepatitis C virus in kidney recipients: epidemiology and impact on renal transplantation. J Hepatol 1992;15:202-206
   CrossRef | Web of Science | Medline

3. 3

   Roth D, Zucker K, Cirocco R, et al. The impact of hepatitis C virus infection on renal allograft recipients. Kidney Int 1994;45:238-244
   CrossRef | Web of Science | Medline

4. 4

   Morales JM, Munoz MA, Castellano G, et al. Impact of hepatitis C in long-functioning renal transplants: a clinicopathological follow-up. Transplant Proc 1993;25:1450-1453
   Web of Science | Medline

To the Editor:

Gane et al. note that persistent HCV infection can damage liver grafts severely and that such damage is more frequent in patients infected with HCV genotype 1b than in those with other genotypes. These authors make no mention of treatment with interferon before transplantation or of whether treatment with interferon or other antiviral agents was instituted in any patient when HCV RNA was detected after transplantation. If such treatment was administered, did it confer a significant advantage in this subgroup? Were levels of viral RNA measured? If they were, did a high level of RNA correlate with graft injury? The levels of HCV RNA and the HCV genotype have been found to be independent prognostic indicators of the response to interferon.1

Michael A. Heneghan, M.B.
University College Hospital, Galway, Ireland

1 References

1. 1

   Marcellin P, Martinot M, Pouteau M, et al. HCV genotype and pretreatment serum HCV RNA level are the main and independent prognosis factors of sustained response to interferon in chronic hepatitis C. Hepatology 1994;20:Suppl:208A-208A abstract.
   Web of Science

Author/Editor Response

The authors reply:

To the Editor: The data of Pol and colleagues extend our observations of the effect of HCV infection after liver transplantation. Such infection can be associated with the accelerated development of substantial liver damage, including cirrhosis. After a mean follow-up of more than 5 years (84±54 months in their study), HCV-infected patients may have significantly worse survival than patients without HCV infection. The rapid progression to cirrhosis in both liver-transplant recipients and renal-transplant recipients can be compared with the acceleration of liver disease reported in patients with AIDS1 and patients with common variable immunodeficiency,2 and it may be due to the effects of immunosuppression on viral replication and the host immune response.

In reply to Heneghan, who asks about HCV RNA levels: our study was a retrospective analysis of all cases of HCV infection after liver transplantation over a long period. In serum samples collected and stored for so long, HCV viremia cannot be reliably quantitated. We addressed this issue in a prospective study that focused on the serial quantitation of HCV RNA in 25 patients undergoing liver transplantation to treat HCV-related cirrhosis.3 The observed association among acute lobular hepatitis, the increased expression of HCV antigens in hepatocytes, and peak levels of HCV RNA in serum suggested that acute hepatitis in the graft is associated with increased viral replication, as has been demonstrated with acute hepatitis in patients without transplants who have transfusion-acquired HCV infection.4

Antiviral prophylaxis has not yet been used at our unit to prevent recurrent HCV infection after liver transplantation for HCV-related cirrhosis or hepatocellular carcinoma. We have considered antiviral treatment only for patients with progressive graft damage, usually on the basis of a liver biopsy one year after transplantation. A small number of the patients we described received interferon or ribavirin as part of a pilot clinical trial. Antiviral treatment was not given when acute hepatitis C was diagnosed in the graft for three reasons. First, acute hepatitis occurred in the majority of patients and was not predictive of the long-term outcome. Second, the biochemical graft dysfunction and histologic inflammation resolved spontaneously in most patients. Finally, acute hepatitis occurred early after orthotopic liver transplantation (within one to six months), the time when any potential risk of allograft rejection due to immunostimulatory drugs would be highest.

Edward J. Gane, M.B., Ch.B.
Nikolai V. Naoumov, M.D.
Roger Williams, M.D.
King's College School of Medicine and Dentistry, London SE5 9RS, United Kingdom

4 References

1. 1

   Eyster ME, Fried MW, DiBisceglie AM, Goedert JJ. Increasing hepatitis C virus RNA levels in hemophiliacs: relationship to human immunodeficiency virus infection and liver disease. Blood 1994;84:1020-1023
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2. 2

   Bjoro K, Froland SS, Yun Z, Samdal HH, Haaland T. Hepatitis C infection in patients with primary hypogammaglobulinemia after treatment with contaminated immune globulin. N Engl J Med 1994;331:1607-1611
   Full Text | Web of Science | Medline

3. 3

   Gane EI, Naoumov NV, Qian KP, et al. A longitudinal analysis of hepatitis C virus replication following liver transplantation. Gastroenterology 1996;110:167-177
   CrossRef | Web of Science | Medline

4. 4

   Naito M, Hayashi N, Hagiwara H, et al. Serial quantitative analysis of serum hepatitis C virus RNA level in patients with acute and chronic hepatitis C. J Hepatol 1994;20:755-759
   CrossRef | Web of Science | Medline

Citing Articles (7)

Citing Articles

1. 1

   Seyed Mohammadmehdi Hosseini Moghaddam, Seyed Moayed Alavian, Nahid Arjmand Kermani. (2008) Hepatitis C and renal transplantation: a review on historical aspects and current issues. Reviews in Medical Virology 18:6, 375-386
   CrossRef

2. 2

   Donatella Ciuffreda, Denis Comte, Matthias Cavassini, Emiliano Giostra, Leo Bühler, Monika Perruchoud, Markus H. Heim, Manuel Battegay, Daniel Genné, Beat Mulhaupt, Raffaele Malinverni, Carl Oneta, Enos Bernasconi, Martine Monnat, Andreas Cerny, Christian Chuard, Jan Borovicka, Gilles Mentha, Manuel Pascual, Jean-Jacques Gonvers, Giuseppe Pantaleo, Valérie Dutoit. (2008) Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication. European Journal of Immunology 38:10, 2665-2677
   CrossRef

3. 3

   Hina Sahi, Nizar N. Zein, Atul C. Mehta, Holli C. Blazey, Kathryn H. Meyer, Marie Budev. (2007) Outcomes After Lung Transplantation in Patients With Chronic Hepatitis C Virus Infection. The Journal of Heart and Lung Transplantation 26:5, 466-471
   CrossRef

4. 4

   R.K. Sharma, S.B. Bansal, A. Gupta, S. Gulati, A. Kumar, N. Prasad. (2006) Chronic hepatitis C virus infection in renal transplant: treatment and outcome. Clinical Transplantation 20:6, 677-683
   CrossRef

5. 5

   Stephen C. Rayhill, Patricia A. Kirby, Michael D. Voigt, Douglas R. La Brecque, Charles T. Lutz, Daniel A. Katz, Frank A. Mitros, Roberto S. Kalil, Rachel A. Miller, Alan H. Stolpen, Dennis Heisey, You Min Wu, Warren N. Schmidt. (2005) Positive Serum Cryoglobulin Is Associated with Worse Outcome after Liver Transplantation for Chronic Hepatitis C. Transplantation 80:4, 448-456
   CrossRef

6. 6

   Nassim Kamar, Lionel Rostaing, Laurent Alric. (2004) Hépatite virale C et transplantation rénale. Gastroentérologie Clinique et Biologique 28:2, 120-125
   CrossRef

7. 7

   Nassim Kamar, Karine Sandres-Saune, Janick Selves, David Ribes, Olivier Cointault, Dominique Durand, Jacques Izopet, Lionel Rostaing. (2003) Long-term ribavirin therapy in hepatitis C virus-positive renal transplant patients: effects on renal function and liver histology. American Journal of Kidney Diseases 42:1, 184-192
   CrossRef