*Purpose: Recent trials have successfully utilized a strategy of hepatitis C virus (HCV) D+ [Donor nucleic acid test (NAT) positive]/R- (Recipient NAT negative) kidney and/or pancreas transplants followed by 8-12 weeks of pangenotypic direct-acting antiviral (DAA) therapy. One concern with ‘real-world application’ of these trials is a delay in timely access to DAAs. This early HCV viremia has been associated with abnormal liver function and development of de-novo donor specific antibody (DSA). We have previously shown a low transmission rate of 4% with a prophylactic peri-operative 7-day DAA regimen (+/- ezetimibe) for ‘kidney-only’ transplants. Ezetimibe, a cholesterol lowering drug, was utilized as it has been shown to restrict HCV entry in hepatocytes in a humanized mouse model. Here, we present our early experience using the same strategy for simultaneous kidney/pancreas transplants (SKPT), where the risk of transmission is conceivably higher, due to a cumulative higher HCV load delivered with dual-organ transplantation.

*Methods: Of 12 eligible SKPT candidates, 10 (83%) agreed to accept HCV NAT+SKPT offers. Inclusion criteria included: a) De-novo transplant; b) Calculated panel reactive antibody≤50%; c) absence of synthetic liver dysfunction; and c) absence of chronic viral infections. The primary outcome was donor HCV transmission at 90 days post-transplant. Secondary outcomes included post-transplant organ function, development of de-novo DSA and acute rejection. Patients were screened with HCV NAT at Day 7, 14, 28 and 90 post-transplant. All subjects received an initial dose of sofosbuvir/velpatasvir (SOF/VEL) + ezetimibe on day 0 no more than 6 hours prior to transplant and then daily for a total of 7 days. Immunosuppression included induction anti-thymocyte globulin followed by maintenance tacrolimus, mycophenolate and steroids. The protocol mandated initiation of full-course DAA therapy in case of 2 consecutive positive NAT tests.

*Results: Of the 10 candidates, 4 received HCV NAT+ SKPT (mean donor age: 27 years; mean KDPI 28%) at a median of 4.7 months post consent. All patients had immediate graft functions of both transplanted organs. At a median follow-up of 7 months post-transplant all patients maintained excellent graft functions. All subjects remained negative for HCV at monitored time points including at 90 days post-transplant, resulting in a HCV transmission rate of 0%. One patient had acute kidney injury due to biopsy proven thrombotic microangiopathy at 1-month post-transplant, that improved with, conversion of tacrolimus to belatacept. There were no episodes of acute rejection, graft loss or de-novo DSA formation.

*Conclusions: This early experience suggests that ultra-short duration 7-day per-operative DAA prophylaxis with SOF/VEL can be successfully used for patients with simultaneous kidney/pancreas transplants. These data are limited by a small sample size, single-center design and absence of donor virologic data.

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