Reviewed by Dr. Christopher Scoma
Goldberg, David S., et al. New England Journal of Medicine 376.24 (2017): 2394-2395

SUMMARY
The THINKER (Transplanting Hepatitis C Kidneys into Negative Kidney Recipients) trial was an open-label, single-group, pilot trial at the University of Pennsylvania that enrolled hepatitis C virus (HCV)-negative patients with end-stage renal disease on the waiting list for kidney transplantation (n=10). Study participants consented to receive single kidney transplantation from deceased donors with untreated HCV genotype 1 infection. The primary outcome of the study was rate of HCV cure after transplantation; secondary outcome was renal allograft function at 6 months post-transplantation.

Transplant recipients received induction therapy with intravenous glucocorticoids and rabbit anti-thymocyte globulin, followed by oral tacrolimus, mycophenolate mofetil, and prednisone. Three days after transplantation, 100% (10/10) recipients had detectable plasma HCV RNA ranging from 15 IU/mL to 193,000 IU/mL. Elbasvir–grazoprevir was initiated in all recipients once HCV viral load was detected, and therapy was maintained for 12 weeks. All recipients were cured of HCV (defined as sustained virologic response 12 weeks after end of treatment).

Recipient serum creatinine at 6 months post-transplantation ranged from 0.8-1.3mg/dL (median 1.1mg/dL); eGFR ranged from 51.8-83.1 mL/min (median 62.8mL/min). One patient experienced delayed graft function, another developed transient class I donor-specific antibodies, another with pre-transplant IgA nephropathy developed post-transplant proteinuria with focal segmental glomerulosclerosis on renal biopsy, and two recipients had transiently elevated aminotransferase levels.

COMMENTARY
The availability of donor kidneys for transplantation is limited, and over 500 deceased donor kidneys go unused every year because donors were infected with Hepatitis C (Reese et al.). The transmission rate of Hepatitis C from HCV-positive kidney donors to HCV-negative recipients is significant at 57-96% (Pereira et al.). However, recent advances in HCV therapy have led to cure rates of >90% using orally-administered, well-tolerated interferon-sparing regimens (Li and De Clercq). These developments have led to postulation that safe transplantation of organs from HCV-infected donors into HCV-uninfected recipients may be feasible.

The THINKER study evaluated the transplantation of kidneys from HCV-infected donor patients into HCV-negative recipients. It found that recipients receiving HCV-infected kidneys can be cured of transplant-associated HCV infection and maintain stable allograft function at 6 months post-transplantation. Drawbacks of this study include small sample size and the relatively short follow-up period. While the long-term implications of HCV-infected kidney transplantation remain to be seen, this is a promising area of research that has the potential to change thousands of lives.

REFERENCES
1. Reese, P. P., et al.”Transplanting Hepatitis C-Positive Kidneys.” N Engl J Med 373.4 (2015): 303-5.
2. Pereira, B. J., et al. “A Controlled Study of Hepatitis C Transmission by Organ Transplantation. The New England Organ Bank Hepatitis C Study Group.” Lancet 345.8948 (1995): 484-7.
3. Li, G., and E. De Clercq. “Current Therapy for Chronic Hepatitis C: The Role of Direct-Acting Antivirals.” Antiviral Res 142 (2017): 83-122.

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