Outcomes of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants

Abstract

Trials describing 4-to 12-week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R− transplants) may be limited in "real-world" application by costs and delayed access to DAAs. We previously reported HCV transmission of 13% among D+/R− transplants with 2-to 4-day pangenotypic sofosbuvir/velpatasvir (SOF/VEL) perioperative prophylaxis, where one patient with HCV transmission was a nonresponder to first-line full-course DAA. Here, we report new data with a 7day prophylaxis protocol (N = 50), as well as cumulative treatment and outcome data on all HCV D+/R− transplants (N = 102). Overall, nine patients (9/102; 9%; 95% CI: 5%-16%) developed HCV transmission, with a significant decline noted in the 7-day group (2/50; 4%; 95% CI: 0%-13%) compared with 2-to 4-day prophylaxis (7/52; 13%; 95% CI: 5%-25%). All patients with HCV transmission achieved sustained virologic response post full-course therapy (including one nonresponder from initial trial). A 1:1 matched analysis (N = 102) with contemporary HCV D−/R− transplants (controls) showed that although the pretransplant wait time was significantly shorter for D+/ R− compared with D−/R− (mean: 1.8 vs. 4.4 years; p < .001), there were no differences in infections, rejection, development of de novo donor-specific antibody, or transplant outcomes up to 6 months of transplant.

Caregiver exposure to hepatitis C virus following transplantation with hepatitis C viremic donor organs: A case series

“…Sexual transmission of HCV is more rare but can occur 27 . Given the rapid reduction in recipient viral loads following initiation of DAA therapy, this case series underscores the importance of instituting DAA therapy as early as possible following HCV D+/R– transplantation 1,28–30 . When DAAs have been used prophylactically (initiated immediately prior to transplantation), recipients had much lower peak viral loads; in some cases, viremia was never detectable 1,17,28 .…”

“…27 Given the rapid reduction in recipient viral loads following initiation of DAA therapy, this case series underscores the importance of instituting DAA therapy as early as possible following HCV D+/R-transplantation. 1,[28][29][30] When DAAs have been used prophylactically (initiated immediately prior to transplantation), recipients had much lower peak viral loads; in some cases, viremia was never detectable. 1,17,28 It is possible that the risk of athome transmission to a caregiver could be eliminated if recipient HCV viremia was cleared prior to hospital discharge.…”

Pan-genotypic direct-acting antivirals for patients with hepatitis C virus infection and chronic kidney disease stage 4 or 5

“…Because the SVR 12 rate in the DAPPeR trial was suboptimal, the investigators conducted the REFORM HEPC trial by extending the prophylactic SOF/VEL to 8 days with or without ezetimibe combination in 50 participants. The SVR 12 rates increased to 94% and 97% in participants receiving SOF/VEL with and without ezetimibe combination [ 95 ]. Patient tolerance was excellent in both trials (Table 4 ).…”

“…Because the antiviral responses with prophylactic or preemptive DAAs are nearly 100%, there have been no clinical trials to evaluate the efficacy and tolerance of SOF/VEL/VOX for HCV-negative recipients who received HCV-positive kidneys. Only five patients who received SOF/VEL/VOX for 12 weeks, of whom three relapsed in DAPPeR and REFORM HEPC trials, were reported in real-world studies, which showed an overall SVR 12 rate of 100% (Table 4 ) [ 91 , 92 , 95 ].…”

Ultrashort Duration Prophylaxis for Hepatitis C Donor Positive to Recipient Negative Simultaneous Kidney/Pancreas Transplants

“…We have previously shown a low transmission rate of 4% with a prophylactic perioperative 7-d DAA regimen ( ±ezetimibe) for "kidney-only" transplants. 5 Ezetimibe, a cholesterol-lowering drug, was used, as it has been shown to restrict HCV entry in hepatocytes in a humanized mouse model. 6 Here, we present our early experience using the same strategy for simultaneous kidney/ pancreas transplants (SKPT), where the risk of transmission is conceivably higher because of a cumulative higher HCV load delivered with dual-organ transplantation.…”