Abstract

Background: The ongoing overdose crisis has led to an increase in transplantation of organs from HCV-infected donors (D+) to uninfected recipients (R-). We previously showed that an ultra-short course (1 day pre and 7 days post) of glecaprevir/pibrentasvir (G/P) combined with ezetimibe (E) prevented chronic infection in non-liver solid organ recipients. We report our results for 2 cohorts: extended follow-up for patients in the original study (n=30), as well as outcomes since adoption of the “Toronto Protocol” as standard of care (SOC) (n=58).

Methods: All D+/R- organ recipients who received the Toronto Protocol with G/P+E x1 dose pre- and daily for 7 days post-transplant were followed to last HCV RNA result or patient death. The primary endpoint was establishment of chronic HCV infection, defined as positive HCV RNA 12 weeks post-transplant or need for retreatment. Additional outcomes include graft rejection and patient survival.

Results: Since adoption of the protocol as standard of care, 58 patients received D+/R- organ transplants from 42 donors. The SOC cohort included 34 (59%) males and 24 (41%) females. The mean age was 57 years (range 22-80), with 32 kidney, 14 lung, 6 heart, 3 pancreas, and 3 kidney-pancreas organ transplants. All non-kidney and 26 (81%) of kidney transplants completed the full treatment regimen before hospital discharge with no dose reductions or treatment discontinuation. All patients had undetectable HCV RNA 2 weeks post-transplant and at last follow-up; median 65 weeks (range 2-171 weeks). 27 (46%) patients developed HCV antibodies that persisted post-treatment. There were 3 deaths unrelated to HCV treatment reported at 11, 188, and 286 days post-transplant and 10 episodes of biopsy-proven rejection, all after completion of HCV therapy.

The initial trial included 30 recipients from 18 donors. With extended follow-up to 220 weeks (median 186 weeks; IQR 56-317), no patients developed chronic HCV infection or relapsed. The 6- month patient survival rate was 93%. There was no graft loss, but 14 (24%) patients died from 7 to 178 weeks post-transplant with no HCV-related deaths.

In total, 88 organ recipients have completed the G/P+E protocol with no virological breakthrough or need for retreatment and no HCV-related complications.

Conclusion: An ultra-short regimen of G/P+E prevented chronic HCV infection in all D+/R- transplant recipients and was well tolerated, allowing the majority to complete treatment before hospital discharge. These results support the current AASLD/IDSA guidance recommendation to initiate treatment promptly after transplantation.