Single Patient Protocol for Donor HCV-positive to Recipient HCV-negative Kidney Transplant in a Patient at Risk for Loss of Dialysis Access
Single Patient Protocol for Donor HCV-positive to Recipient HCV-negative Kidney Transplant in a Patient at Risk for Loss of Dialysis Access
This is a single patient, single center study evaluating if administration of pan-genotypic
 DAA therapy on day 3 (+/- 2 days) post-kidney transplant prevents the transmission of
 hepatitis C virus infection from an HCV-positive donor kidney to an HCV-negative recipient.
The patient selected for this study previously received a kidney transplant under protocol
 2016P002051. Unfortunately, she experienced primary graft nonfunction due to a renal vein
 thrombus and acute thrombotic microangiopathy and the transplanted HCV+ kidney was removed.
 She continued glecaprevir and pibrentasvir for the full course (8 weeks of treatment) and was
 cured of HCV. However, she continues on dialysis requiring ongoing, albeit low dose,
 immunosuppression after her failed transplant. This causes increased risk of infection and
 other dialysis-related morbidity. Futhermore, she is at risk of access loss due to multiple
 failed fistula attempts and prior dialysis catheter line thrombosis. Of note, she also failed
 a trial of peritoneal dialysis due to development of a large pleural effusion (a known
 treatment-limiting complication of peritoneal dialysis). Thus, this young patient, is at risk
 of losing dialysis access which could lead to death. The MGH transplant team has now decided
 that she could be retransplanted with alterations in peri-transplant anticoagulation and
 immunosuppression (eculizumab) that they are confident should decrease her risk of
 peri-transplant thrombosis and recurrent TMA. Thus, we desire to expedite her access to
 re-transplant. Through this protocol, this recipient will be given the opportunity to accept
 a kidney that is HCV antibody positive and nucleic acid test (NAT) negative or HCV NAT
 positive and will be treated with oral glecaprevir (300mg)/pibrentasvir (120mg) (G/P,
 MavyretTM) on day 3 (+/- 2 days) post-kidney transplant to prevent the transmission of HCV
 infection at the time of transplant. Our goal is to provide access to kidney transplantation
 as soon as possible, with a donor of any genotype of infection, with elimination of the
 potential HCV infection by therapy used on day 3 (+/- 2 days) in the case of HCV NAT+
 transplant and surveillance and reactive therapy in the case of HCV antibody positive NAT-
 transplant.
Donor Inclusion Criteria:

 -  Detectable HCV Antibody Positivity

 -  KDPI score is less than ≤ 0.650

 -  Traditional Donor Selection Criteria Met - acceptable for transplantation per usual
 evaluation at MGH

 Donor exclusion criteria

 -  Donor has been known to have previously received and failed HCV treatment with a
 direct-acting antiviral agent

 -  Confirmed HIV

 -  Confirmed HBV positive (surface antigen or HBV DNA positive)

 -  Kidney anatomical damage or significant pathology noted during recovery

 -  Significant liver disease or signs of liver decompensation (splenomegaly, ascites)
 noted during recovery (advanced fibrosis or cirrhosis)

 -  Any standard contra-indication to donation noted in donor (significant malignancy,
 unusual infection)

 Recipient Inclusion/Exclusion Criteria

 -  Previously enrolled in IRB 2016P002051 and experienced primary graft nonfunction due
 to renal vein thrombosis and acute thrombotic microangiopathy

 -  Willing and able to sign informed consent