Portal de Periódicos da CAPES

Hepititis C and renal transplantation: The controversy continues

1998; Elsevier BV; Volume: 53; Issue: 5 Linguagem: Inglês

10.1046/j.1523-1755.1998.t01-1-00021.x

1523-1755

Simin Göral, J. Harold Helderman,

HIV/AIDS drug development and treatment

Hepatitis C virus (HCV) infection, the leading cause of post-transplant liver disease, has recently been recognized as one of the major causes of morbidity and mortality in renal transplantation. Most HCV antibody-positive recipients acquire HCV infection before or at the time of transplantation. The prevalence of HCV among patients with end-stage renal disease (ESRD) undergoing dialysis is reported between 12% to 85%, depending on the techniques used such as antibody and RNA assays [1.Roth D. Hepatitis C virus: The nephrologist’s view.Am J Kidney Dis. 1995; 25: 3-16Abstract Full Text PDF PubMed Scopus (121) Google Scholar, 2.Chan T.M. Lok A.S. Cheng I.K.P. Chan R.T. Prevalence of hepatitis C virus infection in hemodialysis patients: A longitudinal study comparing the results of RNA and antibody assays.Hepatology. 1993; 17: 5-8Crossref PubMed Scopus (188) Google Scholar, 3.Pol S. Romeo R. Zins B. Driss F. Lebkiri B. Carnot F. Berthelot P. Brichot C. Hepatitis C virus RNA in anti-HCV positive hemodialysis patients: Significance and therapeutic implications.Kidney Int. 1993; 44: 1097-1100Abstract Full Text PDF PubMed Scopus (137) Google Scholar, 4.Jeffers L.J. Perez G.O. De Medina M.D. Ortiz-Interian C.J. Schiff E.R. Reddy K.R. Jimenez M. Bourgoigne J.J. Vaamonde C. Duncan R. Houghton M. Choo Q.L. Hepatitis C infection in two urban hemodialysis units.Kidney Int. 1990; 38: 320-322Abstract Full Text PDF PubMed Scopus (108) Google Scholar]. It has been shown that HCV is transmissible by organ transplantation [5.Pereira B.J.G. Milford E.L. Kirkman R.L. Levey A.S. Transmission of hepatitis C virus by organ transplantation.N Engl J Med. 1991; 325: 454-460Crossref PubMed Scopus (319) Google Scholar, 6.Kirk A.D. Heisey D.M. D’Alessandro A.M. Knechtle S.J. Odorico J.S. Rayhill S.C. Sollinger H.W. Pirsch J.D. Clinical hepatitis after transplantation of hepatitis C virus-positive kidneys.Transplantation. 1996; 62: 1758-1762Crossref PubMed Scopus (20) Google Scholar]. In recipients of kidneys from HCV antibody positive donors, 57 to 96% were tested positive for HCV RNA by polymerase chain reaction (PCR) and 0 to 55% developed post-transplantation liver disease [7.Pereira B.J.G. Levey A.S. Hepatitis C virus infection in dialysis and renal transplantation.Kidney Int. 1997; 51: 981-999Abstract Full Text PDF PubMed Scopus (346) Google Scholar]. There have been controversial reports on the long-term effects of HCV infection on graft and patient survival in kidney transplant recipients. In this issue of Kidney International, Pereira and colleagues analyze the impact of HCV infection on survival of kidney transplant and ESRD patients [8.Pereira B.J.G. Natov S.N. Bouthot B.A. Murthy B.V.R. Ruthazer R. Schmid C.H. Levey A.S. The New England Organ Bank Hepatitis C Study Group Effect of Hepatitis C infection and renal transplantation on survival in end-stage renal disease.Kidney Int. 1998; 53: 1374-1381Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar]. They report that the presence of HCV infection was associated with an increased risk of death in patients referred for renal transplantation, and the effect of transplantation was similar in anti-HCV positive and negative patients. They conclude that anti-HCV positive status is not a contraindication for renal transplantation, which has a beneficial effect on long-term survival in anti-HCV positive patients. The report by Pereira and associates provides new fuel to the controversy as to how HCV infection alters outcomes in ESRD and transplant population [8.Pereira B.J.G. Natov S.N. Bouthot B.A. Murthy B.V.R. Ruthazer R. Schmid C.H. Levey A.S. The New England Organ Bank Hepatitis C Study Group Effect of Hepatitis C infection and renal transplantation on survival in end-stage renal disease.Kidney Int. 1998; 53: 1374-1381Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar]. Two important infection-related outcomes are described by the authors: the relationship of infection to chronic liver disease and to transplant outcome. There have been other reports of progressive liver disease in HCV-infected renal allograft recipients. A study by Morales et al demonstrated that more than 50% of HCV positive renal transplant recipients exhibited a severe pattern including cirrhosis, chronic active hepatitis and chronic persistent hepatitis in liver biopsies indicating the seriousness of HCV infection [9.Morales J.M. Munoz M.A. Castellano G. Colina F. Fuertes A. Andres A. Campo C. Blasco A. Hernandez E. Rodicio J.L. Impact of hepatitis C in long-functioning renal transplants: A clinicopathological follow-up.Transplant Proc. 1993; 25: 1450-1453PubMed Google Scholar]. Older age at transplant, female sex, and morphologic diagnosis of advanced chronic hepatitis were found to be associated with histologic progression to cirrhosis [10.Rao K.V. Anderson W.R. Kasiske B. Dahl A.C. Value of liver biopsy in the evaluation and management of chronic liver disease in renal transplant recipients.Am J Med. 1993; 94: 241-250Abstract Full Text PDF PubMed Scopus (112) Google Scholar]. On the other hand, several other groups have described the absence of dire consequences of HCV infection on patient and graft survival in renal allograft recipients [11.Roth D. Zucker K. Cirocco R. Burke G. Ciancio G. Esquenazi V. Swanson S.J. Miller J. A prospective study of hepatitis C virus infection in renal allograft recipients.Transplantation. 1996; 61: 886-889Crossref PubMed Scopus (89) Google Scholar, 12.Haem J. Berthoux P. Mosnier J.F. Grattard F. Cecillon S. Pozzetto B. Alamartine E. Berthoux F. Clear evidence of the existence of healthy carriers of hepatitis C virus among renal transplant recipients.Transplantation. 1996; 62: 699-704Crossref PubMed Scopus (22) Google Scholar]. A group of HCV-infected ESRD patients (N=14) was prospectively followed for up to two years with pretransplant liver biopsies, and virologic and biochemical parameters post-transplant [11.Roth D. Zucker K. Cirocco R. Burke G. Ciancio G. Esquenazi V. Swanson S.J. Miller J. A prospective study of hepatitis C virus infection in renal allograft recipients.Transplantation. 1996; 61: 886-889Crossref PubMed Scopus (89) Google Scholar]. All patients did well with functioning grafts despite enhanced viral replication and mild increase in liver enzymes. Haem and colleagues followed 62 HCV positive renal transplant recipients with liver biopsies for a mean of 72 months (range 36 to 108 months) [12.Haem J. Berthoux P. Mosnier J.F. Grattard F. Cecillon S. Pozzetto B. Alamartine E. Berthoux F. Clear evidence of the existence of healthy carriers of hepatitis C virus among renal transplant recipients.Transplantation. 1996; 62: 699-704Crossref PubMed Scopus (22) Google Scholar]. Although they found a 42% incidence of chronic active hepatitis, patient and graft survival were not significantly different from HCV negative recipients. At our institution, we found that, despite a predisposition to post-transplant liver disease in recipients with pre-existing HCV infection, overall patient and graft survival were similar in long-term follow up (median follow-up 9 years) in the HCV positive and HCV negative recipients [12.Haem J. Berthoux P. Mosnier J.F. Grattard F. Cecillon S. Pozzetto B. Alamartine E. Berthoux F. Clear evidence of the existence of healthy carriers of hepatitis C virus among renal transplant recipients.Transplantation. 1996; 62: 699-704Crossref PubMed Scopus (22) Google Scholar]. Irrespective of the antibody status, the outcome was poor in patients with associated liver disease. Less controversial has been the variant impact of HCV infection on patient outcomes related to forms of renal replacement. Similar to the report by Pereira et al, in a study by Knoll and colleagues, HCV-positive renal transplant recipients had a better survival compared with HCV-positive patients who were acceptable candidates for transplantation but were on dialysis [14.Knoll G.A. Tankersley M.R. Lee J.Y. Julian B.A. Curtis J.C. The impact of renal transplantation on survival in hepatitis-C positive end-stage renal disease patients.Am J Kidney Dis. 1997; 29: 608-614Abstract Full Text PDF PubMed Scopus (162) Google Scholar]. The importance of these studies lies in using a cohort of dialysis patients for outcome comparison very similar to the transplant group as they were on the transplant waiting list, reducing the possibility that differences discerned were merely a consequence of selection bias. The continuing controversy of the impact of HCV infection on the transplant recipient demands further study and analysis by examining such issues as variant viral strains or geographic differences, and improving our understanding of HCV related liver disease. Nevertheless, the report by Pereira and his colleagues supports the conclusion that transplantation is the preferred mode of renal replacement therapy for HCV positive patients with end-stage renal disease [8.Pereira B.J.G. Natov S.N. Bouthot B.A. Murthy B.V.R. Ruthazer R. Schmid C.H. Levey A.S. The New England Organ Bank Hepatitis C Study Group Effect of Hepatitis C infection and renal transplantation on survival in end-stage renal disease.Kidney Int. 1998; 53: 1374-1381Abstract Full Text Full Text PDF PubMed Scopus (276) Google Scholar].