Clinical trial NCT02669966: Live Kidney Donors With Positive Anti-HCV Antibody, But Negative HCV PCR
Official title: Live Kidney Donors With Positive Anti-HCV Antibody, But Negative HCV PCR
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ESRD
Hepatitis C
Keywords: Kidney Transplantation
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2016-02-01
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maintenance of HCV seronegativity
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: Shands at the University of Florida
state: Florida
Study officials:
affiliation: Univesity of Florida
name: Karl Womer, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Schold J, Srinivas TR, Sehgal AR, Meier-Kriesche HU. Half of kidney transplant candidates who are older than 60 years now placed on the waiting list will die before receiving a deceased-donor transplant. Clin J Am Soc Nephrol. 2009 Jul;4(7):1239-45. doi: 10.2215/CJN.01280209. Epub 2009 Jun 18.
citation: Cruzado JM, Gil-Vernet S, Castellote J, Bestard O, Melilli E, Grinyo JM. Successful treatment of chronic HCV infection should not preclude kidney donation to an HCV negative recipient. Am J Transplant. 2013 Oct;13(10):2773-4. doi: 10.1111/ajt.12400. Epub 2013 Aug 6. No abstract available.
citation: Baid-Agrawal S, Schindler R, Reinke P, Staedtler A, Rimpler S, Malik B, Frei U, Berg T. Prevalence of occult hepatitis C infection in chronic hemodialysis and kidney transplant patients. J Hepatol. 2014 May;60(5):928-33. doi: 10.1016/j.jhep.2014.01.012. Epub 2014 Jan 18.
citation: Halfon P, Martinot-Peignoux M, Cacoub P. The myth of occult hepatitis C infection. Hepatology. 2009 Nov;50(5):1675. doi: 10.1002/hep.23113. No abstract available.
citation: Reddy KR EG, Flamm SL, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post-transplant recurrence: preliminary results of a prospective, multicenter study. Hepatology. 2014;60:200A.