TRANSMISSION OF HEPATITIS-C BY KIDNEY-TRANSPLANTATION - THE RISKS

The use of cadaveric organ donors with positive serologic tests for he patitis C (HCV) has caused considerable debate. We have reviewed the c linical course of 43 EIA1 HCV-negative recipients who received kidney transplants from EIA1 HCV-positive donors (Study). We have attempted t o define the rate of HCV-RNA transmission and to determine the frequen cy of HCV disease transmission as determined by abnormalities in liver function tests. Viral transmission was assessed using serologic assay s for HCV antibody formation (EIA1, EIA2, and Matrix-an automated mult iple antigen immunoblot assay) and with PCR testing for the presence o f HCV-RNA on recipient sera. Liver function was followed longitudinall y in the Study patients and compared with a group of 103 kidney recipi ents of organs from EIA1 HCV-negative donors (Control). Of the Study p atients, 56% became PCR-positive for HCV-RNA, suggesting the transmiss ion of HCV-RNA from the HCV-positive donor. Interpretation of serologi c tests for HCV was complex. Currently available first (EIA1) and seco nd (EIA2) generation serologic assays were always negative. The multip le antigen immunoblot assay (Matrix) had a high positive predictive va lue (93%) for the presence of HCV-RNA transmission, but one-third of M atrix-negative Study patients were PCR-positive (sensitivity = 66%). C urrently, only 38% of recipients have HCV-RNA, suggesting that the vir us may have been cleared by one-third of Study recipients who had circ ulating virus. Traditional tests of liver function (ALT, AST, AP, and GGT) were of limited use in predicting HCV-RNA transmission. Average A ST, AP, and GGT were similar in the two groups. Average ALT was increa sed (93 I/U and 47 I/U) in Study and Control patients, respectively, b ut this difference was not significant. Episodes of abnormal liver fun ction (ALT 60-99 IU for greater-than-or-equal-to 14 days) occurred in 22% of Study and 10% of Control patients (P=NS) and lasted longer in S tudy compared with Control patients (301 vs. 138 days; P<0.02). Hepati tis (ALT greater-than-or-equal-to 100 IU for >14 days) occurred with a n equal frequency (6.5%) in both groups. The presence of HCV-RNA did n ot predict episodes of abnormal liver function. Fulminant hepatitis or rapidly progressive cirrhosis did not occur in the recipients of orga ns 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 as ymptomatic HCV infection. Liver disease was not more common in recipie nts of HCV-positive donor organs except for an increased incidence of chronically elevated GGT. The short-term clinical effects (average fol low-up 2 years) of receiving a kidney from an HCV-positive donor appea r to be slight. The long-term effects are difficult to predict due to the lack of understanding of the biology of asymptomatic infection in serologically negative patients on chronic immunosuppression. Several of these factors may ultimately have an impact on the natural history of HCV infection.