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Transmission of hepatitis C by kidney transplantation--the risks
R J Tesi1, K Waller, C J Morgan
1Department of Surgery, Ohio State University, Columbus 43210.
Insights
Kidney transplants from hepatitis C virus (HCV)-positive donors efficiently transmit HCV-RNA to recipients. Most recipients develop asymptomatic HCV infection, with limited impact on liver function tests.
Area of Science:
- Transplantation immunology
- Virology
- Hepatology
Background:
- The use of organs from hepatitis C virus (HCV)-positive donors for transplantation is controversial.
- Understanding HCV transmission dynamics and clinical outcomes in recipients is crucial for donor selection protocols.
Purpose of the Study:
- To assess the rate of HCV-RNA transmission from HCV-positive kidney donors to HCV-negative recipients.
- To evaluate the frequency of HCV disease transmission using liver function tests.
- To analyze the diagnostic performance of serologic assays and PCR for HCV detection post-transplant.
Main Methods:
- A cohort study involving 43 kidney transplant recipients from HCV-positive donors (Study group) and 103 from HCV-negative donors (Control group).
- Viral transmission assessed via serologic assays (EIA1, EIA2, Matrix) and HCV-RNA PCR.
- Longitudinal monitoring of liver function tests (ALT, AST, AP, GGT) in both groups.
Main Results:
- 56% of Study patients tested PCR-positive for HCV-RNA, indicating efficient viral transmission.
- The Matrix assay showed high positive predictive value (93%), but sensitivity was limited (66%).
- Abnormal liver function episodes occurred more frequently and lasted longer in Study patients, though severe hepatitis was similar between groups. HCV-RNA presence did not predict abnormal liver function.
Conclusions:
- Kidney transplantation from HCV-positive donors leads to a high rate of HCV-RNA transmission.
- Most recipients develop asymptomatic HCV infection, with minimal severe liver disease observed.
- Current serologic tests have limitations; PCR is essential for detecting transmission. Liver function tests have limited utility in predicting transmission or disease severity.
Abstract:
The use of cadaveric organ donors with positive serologic tests for hepatitis C (HCV) has caused considerable debate. We have reviewed the clinical course of 43 EIA1 HCV-negative recipients who received kidney transplants from EIA1 HCV-positive donors (Study). We have attempted to define the rate of HCV-RNA transmission and to determine the frequency of HCV disease transmission as determined by abnormalities in liver function tests. Viral transmission was assessed using serologic assays for HCV antibody formation (EIA1, EIA2, and Matrix--an automated multiple antigen immunoblot assay) and with PCR testing for the presence of HCV-RNA on recipient sera. Liver function was followed longitudinally in the Study patients and compared with a group of 103 kidney recipients of organs from EIA1 HCV-negative donors (Control). Of the Study patients, 56% became PCR-positive for HCV-RNA, suggesting the transmission of HCV-RNA from the HCV-positive donor. Interpretation of serologic tests for HCV was complex. Currently available first (EIA1) and second (EIA2) generation serologic assays were always negative. The multiple antigen immunoblots assay (Matrix) had a high positive predictive value (93%) for the presence of HCV-RNA transmission, but one-third of Matrix-negative Study patients were PCR-positive (sensitivity = 66%). Currently, only 38% of recipients have HCV-RNA, suggesting that the virus may have been cleared by one-third of Study recipients who had circulating virus. Traditional tests of liver function (ALT, AST, AP, and GGT) were of limited use in predicting HCV-RNA transmission. Average AST, AP, and GGT were similar in the two groups. Average ALT was increased (93 I/U and 47 I/U) in Study and Control patients, respectively, but this difference was not significant. Episodes of abnormal liver function (ALT 60-99 IU for > or = 14 days) occurred in 22% of Study and 10% of Control patients (P = NS) and lasted longer in Study compared with Control patients (301 vs. 138 days; P < 0.02). Hepatitis (ALT > or = 100 IU for > 14 days) occurred with an equal frequency (6.5%) in both groups. The presence of HCV-RNA did not predict episodes of abnormal liver function. Fulminant hepatitis or rapidly progressive cirrhosis did not occur in the recipients of organs from HCV-positive donors. These data demonstrate a high efficiency of transfer of HCV-RNA by kidney transplantation from an HCV-positive donor to an HCV-negative recipient. A majority of the patients have asymptomatic HCV infection.(ABSTRACT TRUNCATED AT 400 WORDS)