Hepatitis C virus (HCV) RNA level in plasma and kidney tissue in HCV antibody‐positive donors: Quantitative comparison

Abstract

Kidney transplant from donors with hepatitis C virus (HCV) antibody has been limited to HCV viremic recipients only, due to concern of the HCV transmission. However, the new antiviral medications provide an opportunity to expand the utilization of these donors. To study the risk of HCV transmission in kidney transplantation, we used discarded donor kidneys and determined HCV RNA levels by quantitative real-time PCR in bilateral (right and left) kidney biopsies and plasma from 14 HCV antibody-positive donors (sensitivity: 15 international unit (IU)/mL plasma; 1.8 IU/50 nL kidney). In three NAT-negative donors, HCV RNA was negative in plasma and kidney. In all 11 NAT-positive donors, HCV RNA was positive in plasma (range: 5807-19 134 177 IU/mL) but negative in six kidneys from four donors with plasma HCV RNA <1.5 million IU/μL. HCV RNA correlated between right and left kidneys (P = 0.75) and between kidney and plasma (r = 0.86). When normalized by volume, HCV RNA median (range) was 49 (0-957) IU/50 nL plasma and 1.0 (0-103) IU/50 nL kidney, significantly lower in kidney (P = 0.005) than in plasma (14-fold). Plasma HCV RNA can be used to predict the kidney HCV load. Future studies are needed if plasma/kidney HCV levels can be used to stratify donors for transmission risk and recipients for post-transplant management in extended utilization of HCV antibody-positive donors.

Assessing Tissue Transmission of Hepatitis C Virus From Viremic Donor to Seronegative Kidney Transplant Recipients: A Case Series

“…In our group, viral RNA was detected in D5 kidney tissue, but not in D6, from the same donor (Table 2), Shike's experience is similar to ours, as they also detected the virus in the tissue of one but not both kidneys in two of their donors [13]. These authors [13], like us, attribute the cases of nondetection of the virus in tissue to the low viral load present in extrahepatic tissues [16] and to the lower sensitivity of the tissue detection technique [13].…”

“…Compared to our study, Shike et al's [13] has the advantage of having a large amount of tissue on which the virus could be detected, since it included kidneys rejected for transplantation instead of on graft cylinders for transplantation.…”

“…As Wrobleswska et al [ 16 ] have described, the volume of the samples determines the sensitivity of the technique. The number of viral particles in extrahepatic tissues is very low [ 13 , 16 ], and in our case, the samples were small.…”

“…The presence of HCV in the extrahepatic tissue of viremic patients has scarcely been studied, but several authors have described it in gastrointestinal mucosa [ 7 ], lymph nodes [ 8 , 9 ], bone marrow [ 10 ], the central nervous system [ 11 ], the pancreas, heart, and even kidney [ 12 , 13 ]. In addition, some authors have observed the presence of negative-polarity RNA in extrahepatic tissue [ 7 , 12 , 15 ], which acts as an intermediary in the replication of the virus, confirming the possibility of transmitting the active infection [ 15 ].…”

“…Administration of direct-acting antivirals (DAA) to the recipient pre-transplant prevents post-transplant viremia and possibly transmission of infection [3,4]; however, starting treatment in the post-transplant period prevents neither viremia nor the consequent transmission [5,6]. In addition to detecting viral particles in different extrahepatic compartments, including kidney tissue, several studies have also observed viral replication [7][8][9][10][11][12][13], which could enable the transmission of the infection in the absence of viremia through the tissue of kidney grafts.…”