Live Kidney Donors With Positive Anti-HCV Antibody, But Negative HCV PCR

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.