Live Kidney Donors With Positive Anti-HCV Antibody, But Negative HCV PCR
Condition: ESRD; Hepatitis C
MeSH terms: Hepatitis C
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Kidney transplantation
Intervention type(s): Procedure
Intervention description(s): Once the donor and recipient candidates have met inclusion criteria and cleared study-specific as well as standard of care screening, they will proceed to live-donor kidney transplantation and subsequent post-transplant monitoring
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Kidney Transplantation