Live Kidney Donors With Positive Anti-HCV Antibody, But Negative HCV PCR
Live Kidney Donors With Positive Anti-HCV Antibody, But Negative HCV PCR
It is well recognized that a subset of patients who contracts Hepatitis C virus (HCV)
 spontaneously clears the virus. Such individuals are anti-HCV antibody positive, yet HCV RNA
 PCR negative in the blood. While they have not been considered candidates for live kidney
 donation in the past, with the recent availability of novel anti-HCV drugs with >95% cure
 rates, they now represent a potential pool of donor candidates, especially since the risk for
 transmission of HCV to the recipient is extremely low. The investigators goal is to
 demonstrate that live kidney donation from anti-HCV positive, HCV RNA PCR negative
 individuals is safe and carries a negligible risk of viral transmission to the recipient.
Individuals who test positive for anti-HCV IgG antibody, but who have negative blood HCV RNA
 PCR are generally considered to have been infected with HCV but to have cleared the the virus
 spontaneously. However, due to the general conservative approach of living donor kidney
 transplant programs, these individuals are not considered potential live kidney donors,
 despite being considered at extremely low risk for HCV transmission to the recipient. This
 reluctance stems from past experiences with post-transplant HCV complications, both hepatic
 (e.g. cirrhosis) and extra-hepatic (e.g. transplant glomerulonephritis) and from the fact
 that the historical mainstay of HCV treatment, interferon, was poorly tolerated, had low cure
 rates, and caused transplant rejection. Now, however, highly effective novel therapeutics may
 transform the way transplant physicians and patients think about HCV-positive donated
 kidneys.

 With these new agents, the current cure rates for HCV now exceed 95%. A recent report
 demonstrated high cure rates even in the liver transplant setting, suggesting that
 immunosuppression does not impede eradication and that interactions between HCV and
 transplant drugs can be successfully managed. Thus, while the risk of transmission of
 infection from anti-HCV antibody positive, HCV PCR-negative is not known, if transmission
 were to occur, treatment is now possible, to the point where transplant professionals are
 beginning to advocate using anti-HCV Ab positive individuals as donors for HCV-negative
 recipients. A group in Barcelona reported transplantation of a live donor kidney from a donor
 treated with an anti-HCV regimen that achieved a sustained virological response to her spouse
 with no transmission of infection.

 The main area of concern seems to be what is described as "occult HCV infection"- the
 presence of HCV RNA in peripheral blood mononuclear cells and organ tissue by ultrasensitive
 assays in the absence of detectable RNA in the serum. However, this entity is itself
 controversial, and its significance is uncertain, with inadequately described risk of
 transmission. If HCV were transmitted and successfully treated, another concern is the
 potential residual risks of viral complications, even though these have not been evident in
 any previous trials. Finally, a major concern is financial, as HCV treatment currently costs
 more than $80,000 for a 3-month regimen. However, chronic hemodialysis costs upwards of
 $100,000 per year when all costs are considered, while kidney transplantation costs only
 about $20,000 per year after the first year. Thus, over time, even after treatment for CMV
 infection, if it is required, kidney transplantation would result in an overall cost savings
 to the health care system.

 Given the unknown, though generally considered very low risk of transmission of HCV from an
 antibody-positive, PCR-negative individual, combined with the wide availability of effective
 treatment for HCV infection, it is felt that the recipient is not exposed to a high risk of
 infection in such a transplant. Furthermore, this small risk needs to be weighed against the
 risk of staying on dialysis, which carries a mortality rate of 6.5-7.4 times that of the
 general population and 4.6-5.9 times that of the renal transplant population. The case
 becomes even more compelling when considering patients with a high risk of deterioration if
 they continue dialysis (elderly, diabetics, and those with cardiovascular disease),
 disadvantageous blood types, and those with broad sensitization, with extremely limited
 compatible donor options. Given the proven survival benefit of kidney transplantation in
 patients with chronic HCV, there is ample reason to believe that providing HCV positive
 kidneys and HCV therapy (if indeed required) to HCV negative recipients will lead to better
 outcomes than those associated with remaining on dialysis.
Inclusion Criteria:

 Donor inclusion criteria:

 -  The donor candidate must be anti-HCV positive by ELISA and HCV RNA negative by PCR,
 with both tests repeated for confirmation, as per standard protocol.

 -  The donor must be evaluated and cleared by Hepatology, which is currently the standard
 of care for HCV seropositive individuals.

 -  The donor must meet criteria for living kidney donation and be approved by the UF
 Health Shands Kidney Transplant Medical Review Board.

 Recipient inclusion criteria:

 -  The recipient may be HCV antibody negative or anti-HCV antibody positive but HCV RNA
 negative by PCR.

 -  The recipient must meet the criteria for kidney transplantation and be approved by the
 UF Health Kidney Transplant Program Medical Review Board.