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Vol. 29. Issue. 4.August 2009
Pages 285-378
Vol. 29. Issue. 4.August 2009
Pages 285-378
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Interferon-alpha and its deleterious effects on kidney transplant: regarding one case
EL INTERFERÓN ALFA Y SUS EFECTOS DELETÉREOS EN EL TRASPLANTE RENAL: A PROPÓSITO DE UN CASO.
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Pilar Frailea, P. García-Cosmesa, C. Rosadoa, J.M.. Taberneroa
a Servicio de Nefrología, Hospital Universitario de Salamanca Salamanca, Salamanca, España,
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Dear Editor:

The prevalence of chronic infection due to the hepatitis C virus in kidney transplant patients ranges from 5 to 40%.1 Hepatitis C increases the morbimortality in both haemodialysis and kidney transplant patients. Hepatitis C should be treated prior to transplant, since post-transplant treatment with interferon-alpha2 increases the risk of acute humoral rejection, particularly during the immediate post-transplant phase.

We present the case of a 55 year old male with a history of chronic terminal renal failure secondary to mesangial glomerulonephritis IgA, who began haemodialysis in October 1989, arterial hypertension and chronic infection due to hepatitis C virus (genotype 1). The patient received a cadaver kidney transplant in 1997 and began immunosuppressant therapy with OKT3, corticosteroids and cyclosporine. Development following the renal transplant was without incident, with stable renal function (urea 45mg/dL, Cr 0.8mg/dL), negative proteinuria, chronically elevated transaminases, positive RNA-HCV with no evident clinical signs of cirrhosis or advanced hepatopathy, and cyclosporine levels within the therapeutic range. The patient regularly attended digestive reviews, where it was decided to recommend treatment with interferon-alpha and ribavirin for twelve months. His renal function remained stable during this period. Three months following completion of the treatment, renal function deteriorated with 133mg/dL urea, 1.8mg/dL Cr and 1.8g/24h proteinuria, which worsened with later tests (urea 203mg/dL and Cr 2.7mg/dL). Ig and cryglobulin levels and an autoimmune study were all normal. It was decided to admit the patient in order to perform a diagnostic renal biopsy. The differential diagnosis included relapse of mesangial glomerulonephritis IgA, membranous or mesangiocapillary glomerulonephritis caused by the hepatitis C virus, chronic graft nephropathy or acute secondary rejection on treatment of interferon. The renal biopsy revealed acute humoral rejection with C4d+, and Ab anti-HLA levels were positive (22%) against the donor. It was decided to begin treatment with three 25 0mg 6-methylprednisolone tablets and conversion to tacrolimus. The response to treatment was good, with an improvement of renal function: 150mg/dLurea, 2mg/dL CR and a reasonable decrease in proteinuria (1.2g/24h).

The optimum treatment for hepatitis C in renal transplant patients today is controversial. Use of interferon is not advised, since it increases the chance of episodes of acute humoral rejection (15-64%) three to six months after beginning treatment,3 and its use is indicated only in patients with fibrosing cholestatic hepatitis, where there is a significantly increased morbimortality. The incidence of acute humoral rejection is lower in patients with long-developing transplants, owing to immunological accommodation. The mechanism for inducing acute rejection is unclear, but it is thought that the drug increases the release of HLA antigens in the cellular surface and induces the release of cytokines, consequently stimulating the production of antibodies.4 To minimise the risk of rejection, patients should have stable immunosuppression and should be closely monitored.5

The case in question concerns a patient ith a normally functioning kidney transplant and stable renal function who received, twelve years after transplant, treatment with ribavirin and interferon-alpha, with a subsequent episode of humoral rejection. The importance of this case lies in the fact that the acute humoral rejection appeared during the late post-transplant period, and three months after having completed interferon treatment, which is uncommon.

In conclusion, it is of vital importance that nephrologists and digestive specialists know the indications of interferon in the transplant population, weighing up its potential benefits against the risk of rejection, and ensure patients on antiretroviral treatment are more closely monitored, even once this treatment has ended. Safer and more effective treatments are needed for treating renal transplant patients with infection from the hepatitis C virus.

Bibliography
[1]
Baid-Agrawal S, Pascual M, Moradpour D, Frei U, Tolkoff-Rubin N. Hepatitis C virus infection in haemodialysis and kidney transplant patients. Rev Med Virol 2008;18(2):97-115. [Pubmed]
[2]
Sharma RK, Bansal SB, Gupta A, Gulati S, Kumar A, Prasad N. Chronic hepatitis C virus infection in renal transplant: treatment and outcome. Clin Transplant. 2006;20(6):677-83. [Pubmed]
[3]
Fabrizi F, Lunghi G, Dixit V, Martin P. Meta-analysis: anti-viral therapy of hepatitis C virus-related liver disease in renal transplant patients. Aliment Pharmacol Ther 2006;24(10):1413-22. [Pubmed]
[4]
Baid S, Tolkoff-Rubin N, Saidman S, Chung R, Williams WW, Auchincloss H, et al. Acute humoral rejection in hepatitis Cinfected renal transplant recipients receiving antiviral therapy. Am J Transplant 2003;3(1):74-8. [Pubmed]
[5]
Gane E, Pilmore H. Management of chronic viral hepatitis before and after renal transplantation. Transplantation 2002;74(4):427-37. [Pubmed]
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