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Facing challenges: Hepatitis C and Kidney Transplantation

Posted Sep 14 2011 10:57am
Hepatitis C virus (HCV) infection affects more than 180 million people globally, may lead to renal disease and is prevalent in 11-49% of patients with end-stage renal disease, depending on geographical location. With that picture in mind, we are faced with the question of choosing which patients might benefit from kidney transplantation and what is the current literature on that.

A potential recipient is HCV Ab positive. What is the best approach?

Getting a liver biopsy is the most important step after identification of HCV infection, since LFTs and viral loads do not correlate well with degree of liver disease. Despite no clear guidelines, advanced liver disease should be referred for possible liver/kidney transplant. Imaging of the liver is also essential in addition to AFP (higher risk of hepatocellular carcinoma)

Does kidney transplantation provide a survival advantage to HCV infected patients?

Yes. Despite the increased risk of death on the first 6 months after tx, HCV patients have a clear survival advantage , with significant decrease in cardiovascular mortality long-term (HR 0.2, p value below 0.001). Nonetheless, compared to HCV-negative patients, they still carry a higher risk of death (RR 1.79) and graft failure (RR 1.56).

What is the most worrisome complication of HCV infected patients after transplantation?

Using common sense, you might think that with the immunosuppression required by kidney tx, exacerbation of HCV infection would occur more frequently compared to patients on dialysis, with faster progression of liver disease. Indeed, HCV viral load might increase after transplantation, however, this is not associated with increased risk of posttransplantation liver disease. A recent retrospective study of 230 HCV-infected patients indicated that kidney transplantation does not accelerate liver injury, revealing that ~77% of recipients that underwent follow-up liver biopsies showed stable or improved liver histology. Progression of liver injury may be actually lower in tx recipients compared to patients on the waiting list. The most important complication was the increased risk of general infection on the first six months after tx.

What is the best immunosuppressive regimen in these patients?

Unclear at this point, though a subgroup analysis of a retrospective data (huge limitations) suggested lower liver fibrosis progression with Thymo compared to Daclizumab. No difference in maintenance immunosuppression was noted.

Can HCV infection be treated after transplantation?

The use of interferon alfa after transplantation has been associated with a very high risk of acute graft rejection and is currently only recommended for kidney recipients with HCV infection resulting in life-threatening vasculitis or fibrosing cholestatic hepatitis.

In face of organ shortage, could we consider transplanting a HCV + donor kidney to a HCV + recipient?

This is a controversial topic, but recent study suggests that this is a safe long-term strategy for HCV+ patients, in terms of patient survival, graft survival and liver disease.

Novel drugs like Telaprevir might change the natural history of HCV, however, recent study suggested that this protease inhibitor might not be recommended after tx due to significant interactions with CNI (P450 inhibition). It's never that easy...

(picture: day after Irene's storm in Cape Cod )
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