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Serologic responses to hepatitis C virus in solid organ transplant recipients
J K Preiksaitis1, S M Cockfield, J M Fenton
1Medical Microbiology and Public Health, University of Alberta Hospitals, Edmonton, Canada. jkp@bugs.uah.ualberta.ca
Insights
Hepatitis C virus (HCV) infection was frequently transmitted through organ donation and blood transfusions in kidney and heart transplant recipients before 1992. Many patients showed delayed or absent antibody responses, highlighting the need for RNA testing.
Area of Science:
- Transplantation Immunology
- Infectious Diseases
- Virology
Background:
- Hepatitis C virus (HCV) is known to transmit via blood transfusions and organ donation.
- Historical incidence of donor- and transfusion-acquired HCV infection in kidney (RTx) and heart transplant (HTx) recipients was investigated.
- Kinetics of seroconversion to HCV in transplant recipients were studied.
Purpose of the Study:
- To determine the historical incidence of donor- and transfusion-acquired HCV infection in RTx and HTx recipients.
- To analyze the kinetics of seroconversion to HCV in these patient populations.
- To evaluate the effectiveness of screening methods and the utility of HCV RNA assays.
Main Methods:
- Sera from organ donors (n=476) and recipients (preTx, 1-year, and last follow-up) were screened for anti-HCV.
- HCV RNA was assayed using RT-PCR in selected recipients.
- Donor-recipient transmission and seroconversion rates were analyzed.
Main Results:
- Pre-transplant anti-HCV positivity was 6.2% in RTx and 2.3% in HTx donors.
- HCV transmission occurred in 85.7% of infected donors with adequate recipient follow-up.
- Seroconversion to anti-HCV was observed in 6.1% of RTx and 11.1% of HTx recipients; de novo infections occurred in 1.2% of RTx and 6.8% of HTx.
Conclusions:
- HCV infection via organ donation and transfusion was common in RTx and HTx recipients before 1992.
- Serologic responses to HCV were often delayed or absent, with impaired humoral response in HTx recipients.
- HCV RNA assays are recommended for screening in transplant populations due to limitations in serologic detection.
Background:
Hepatitis C (HCV) infection is known to have been transmitted by both blood transfusion and donor organs. We sought to determine the historical incidence of donor- and transfusion-acquired HCV infection in kidney transplant (RTx) and heart transplant (HTx) recipients at our center and to study the kinetics of seroconversion to HCV.
Methods:
A bank of sera collected from organ donors (388 RTx and 88 HTx) who received allografts between January 1984 and April 1992 was screened for anti-HCV using a third generation enzyme immunoassay. Recipient sera collected before transplant (preTx), at 1 year after transplant, and at last follow-up were tested. Fresh follow-up sera on all surviving anti-HCV-positive (+) RTx and HTx, all anti-HCV-negative (-) HTx, and a subset of 85 anti-HCV- RTx were assayed for HCV RNA using an reverse transcriptase-polymerase chain reaction assay.
Results:
Twenty-four of 388 RTx (6.2%) and 2 of 88 HTx (2.3%) were anti-HCV+ preTx. Eight of 218 (3.7%) organ donors were anti-HCV+. Six of the seven (85.7%) anti-HCV+ donors with adequate recipient follow-up transmitted HCV infection to one or more recipients. Nineteen of 313 RTx (6.1%) and 8 of 72 HTx (11.1%) with follow-up > or =1 year seroconverted to anti-HCV. One of 85 (1.2%) anti-HCV- RTx and 3 of 44 (6.8%) anti-HCV-HTx were HCV RNA+ when tested at last follow-up. Five cases of de novo HCV infection occurred after the introduction of first generation anti-HCV screening of donors. Persistent viremia (HCV RNA+) at last follow-up was observed in 70.6% (12/17) RTx anti-HCV+ preTx. Fourteen of 15 (93.3%) RTx and 9 of 9 (100%) HTx with de novo HCV infection had persistent viremia. Seroconversion was more delayed in HTx than RTx (P=0.0572, log-rank Mantel-Cox statistic) although both groups demonstrated an impaired humoral response to HCV when compared with the immunocompetent host.
Conclusions:
Organ donor- and transfusion-acquired HCV infection was common in RTx and HTx transplanted before the introduction of second generation anti-HCV screening in 1992. Serologic responses to HCV are often delayed and sometimes absent in these patients. Assays for HCV RNA should be considered as a screening test for the detection of HCV infection in this population. Serologic responses to HCV were more impaired in HTx compared with RTx, which may reflect the more intensive immunosuppressive regimens given to HTx at our center.