**6. Conclusion**

In regards to superinfection, HCV genotype 1 is the most common genotype of HCV seen in Western countries and is notorious to be less responsive to antiviral therapy including Pegylated IFN and Ribavirin. Some authorities suggest that genotyping should be done routinely and genotype 1 renal allografts should not be used in recipients with other genotypes.

In non-transplant setting, the combination therapy with interferon (IFN) and Ribavirin is the standard of care for treatment of initial as well as relapse of HCV infection. Clearance of Ribavirin is impaired in patients with renal dysfunction as the drug itself and its metabolites cannot be removed by Hemodialysis. Therefore, Ribavirin is not recommended in patients with creatinine clearance of less than 50mL/min. IFN therapy is however recommended in dialysis patients. The goal of pretranslant HCV treatment is to attempt to eradicate HCV before transplant subsequently leading to decrease in the risk of progression of HCV-associated liver disease, reduced risk of posttransplant renal dysfunction, and possible reduction in HCV disease progression. The optimal treatment of HCV in dialysis patients is regarded as IFN therapy but it is not known whether there is any added advantage on the use of pegylated IFN over nonpegylated standard IFN. Dialysis patients are not considered candidates of combi‐ nation therapy owing to concerns regarding development of Ribavirin-induced anemia as the clearance of the drug is impaired in patients with renal dysfunction. A safer but less costeffective approach is to use IFN therapy to treat HCV positive patients on dialysis who are potential transplant candidates. This strategy seems to have a beneficial effect on the course of liver disease posttransplant, shows higher rates of sustained biochemical and virological response, and seems to have reduced risk of HCV disease progression. At present data on relapse rate on HCV positive patients treated pretransplant is limited and controversial. 2008 KDIGO guidelines suggest HCV positive transplant candidates to be considered for IFN therapy before transplant. Ribavirin is not recommended because of its impaired clearance. Similar concerns apply to pegylated IFN because of its longer half-life and is also not recom‐

Posttransplant HCV treatment is generally not recommended. A major limitation to the use of IFN posttransplant is the potential of developing acute rejection. In addition to antiviral activity, IFN also has pleiotropic effects including antiproliferative and immunomodulatory functions. The National Institute of Health (NIH) Consensus Statement on management of HCV infection lists renal transplant as one of the contraindications to IFN therapy. Most authorities are in line with this approach because of the increased risk of acute rejection, high cost, limited efficacy, and significant side effects that are reported with IFN treatment after transplant. Treatment may be recommended in exceptional and life-threatening cases of HCV complications such as fibrosing cholestatic hepatitis, life-threatening vasculitis, recurrent and progressive HCV-associated glomerulopathy in the transplanted kidney, and advanced

However data is limited regarding this strategy (Carbone et al., 2011).

240 Current Issues and Future Direction in Kidney Transplantation

**5. Treatment**

mended for pretransplant HCV therapy.

histologic stages of liver fibrosis.

HCV infection is relatively common among patients with ESRD on dialysis and kidney transplant recipients. It is a major cause of morbidity and mortality among this group. When indicated, treatment with IFN and antiviral therapy should be commenced prior to kidney transplantation. The optimal treatment of transplant patients with HCV infection is not known. IFN is not recommended posttransplant because of potential risk of rejection. However there are some life threatening HCV related complications that would compel the use of IFN in a renal transplant recipient. In conclusion, Ribavirin is contraindicated in dialysis patients and alternative drugs are needed to enhance antiviral effects of IFN. For renal transplant recipients, Ribavirin can be used in combination with IFN in patients with restored renal function, however the risk of acute rejection with IFN therapy remains a serious concern. Alternative drugs are also needed with better safety and efficacy for treatment of HCV posttransplant. Despite the ongoing dilemma HCV positive renal transplant recipients have a better survival than HCV positive patients awaiting transplantation. Data shows strong evidence that use of allografts from HCV positive donors leads to reduced wait time for HCV positive recipients however there is conflicting data about graft and overall survival that needs to be further studied. In addition transplant of kidneys from HCV positive donors should be restricted to recipients with HCV viremia at the time of transplant.

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