Only 49% transmission rate observed in kidney transplants from HCV-positive donors, but lower graft and survival overall

With hepatitis C (HCV) being curable with direct-acting antivirals in eight to 12 weeks or less, the question arises whether we can transplant HCV-positive organs to HCV-negative patients safely with treatment. In a large study of U.S. kidney transplant recipients, five-year graft and patient survival were significantly lower in recipients with an HCV-positive kidney donor. However, of note, the researchers observed a 49% HCV transmission rate, while other studies have shown 100% transmission.

To address the question of whether the limited supply of donors for patients needing kidney transplant could be alleviated by using more kidneys from deceased donors who had HCV infection, U.S. researchers looked at whether that strategy poses a risk of lower transplant survival or greater mortality in HCV-negative transplant recipients. A Virginia Commonwealth University team analyzed the national Organ Procurement and Transplant Network (OPTN) database to compare graft and patient survival in HCV-negative recipients of kidneys from HCV-positive versus negative donors.

The study, which was presented at the Liver Meeting 2016, in Boston, included patients who received kidney-only transplants from April 1994 through June 2014. The researchers matched each recipient of a kidney from an HCV-positive donor to five recipients of kidneys from HCV-negative donors. Matching considered recipient age, gender, race, time on dialysis before transplant and other kidney- and transplant-related factors.

The analysis included 421 HCV-negative recipients of kidneys from HCV-positive donors (HCV D+/R-) and 2105 matched recipients of kidneys from HCV-negative donors (HCV D-/R-). The HCV D+/R- and HCV D-/R- groups were similar in age (mean 55.9 and 56.3 years), proportions of men (72.2% and 72.2%), proportions of African Americans (52.2% and 51.2%), pretransplantation years on dialysis (mean 3.20 versus 3.17 years) and proportions undergoing retransplantation (5.9% and 5.0%).

After five years, graft survival was significantly worse in the HCV D+/R- group than the HCV D-/R- group (43% versus 56%, P < .001), as was five-year patient survival (57% versus 76%, P < .001).

The researchers had post-transplantation HCV antibody data on 126 recipients, 62 (49%) of whom tested positive (probably as a result of the transplant) and 64 (51%) of whom did not. The HCV antibody-positive and negative groups did not differ substantially in age. Time since transplantation was somewhat longer in the HCV antibody-positive group (median 365 versus 310 days). The HCV-positive group included a higher proportion of men (79.0% versus 67.7%), African Americans (67.7% versus 37.1%) and retransplantation patients (6.5% versus 1.6%). Five-year graft survival did not differ significantly between HCV antibody-positive and negative recipients (45% and 49%), nor did patient survival (60% and 64%).

Lack of five-year graft and survival difference between HCV antibody-positive and negative recipients suggested to the researchers that “HCV transmission might not be the primary culprit” for the poor overall graft and patient survival in HCV D+/R- participants.

During his presentation, lead investigator Richard K. Sterling noted, “If we go ahead and transplant hepatitis C-positive organs into hepatitis C-negative patients, what would then be the impact of trying to treat the hepatitis C in that newly acquired infection?” He said, “I think that’s really the key point because certainly there is a significant organ shortage — we’re throwing away a lot of these organs.” “[T]his seems like an ideal strategy to try and expand the donor pool. […] This is something that I think needs to be done,” Sterling concluded.

However, David S. Goldberg, M.D., M.S.C.E., who leads the kidney transplantation program at the University of Pennsylvania, urged that the HCV transmission findings be viewed cautiously because the analysis depended on HCV antibody testing instead of HCV RNA assessment. In Goldberg’s clinical trial experience, 100% of initially HCV-negative recipients of kidneys from HCV-positive donors acquire HCV infection as a result of transplantation when assessed by HCV RNA.

By Mark Mascolini

Original Article