Hepatitis C virus transmission during organ transplantation

Background . There is a high prevalence of liver disease among the recipients of organs from donors with antibodies to hepatitis C virus (HCV). We undertook a study to determine the frequency of persistent HCV infection, as indicated by the presence of HCV RNA, among both cadaveric organ donors positive for antibodies to HCV (anti‐HCV) and the recipients of organs from these donors. Methods . Serum samples from donors and recipients were tested for HCV RNA with the reverse transcriptase polymerase chain reaction, with use of primers from the 5′ untranslated region of the HCV genome, and for anti‐HCV with the first‐generation enzyme‐linked immunosorbent assay (ELISA) and two second‐generation tests. Results . HCV RNA was detected in 9 of 11 organ donors (82 percent) with a positive first‐generation ELISA for anti‐HCV. Among the organ recipients, the prevalence of HCV RNA increased after transplantation: 7 of 26 patients (27 percent) had positive samples before transplantation, as compared with 23 of 24 patients (96 percent) after transplantation (P < 0.001). Among 13 recipients who were HCV RNA–negative before receiving organs from the nine HCV RNA–positive donors, HCV infection was detected in all 13 after transplantation, and anti‐HCV developed in 8 (62 percent). On the basis of a positive test for HCV RNA, the maximal sensitivity of the three anti‐HCV tests was 57 percent (positive in 4 of 7 patients with end‐stage organ failure) before transplantation and 70 percent (positive in 16 of 23 patients) after transplantation. Conclusions . Nearly all the recipients of organs from anti‐HCV–positive donors become infected with HCV. The current tests for anti‐HCV antibodies underestimate the incidence of transmission and the prevalence of HCV infection among immunosuppressed organ recipients. Objective: To determine the prevalence of antibodies to hepatitis C virus (anti‐HCV) and HCV RNA among cadaver organ donors and to correlate these results with donor liver histologic abnormalities and evidence for transmission of disease through organ transplantation. Design: Retrospective testing of stored serum samples from cadaver organ donors for anti‐HCV and HCV RNA. Setting: Transplantation service of the University of Miami/Jackson Memorial Medical Center and other cooperative medical centers furnishing follow‐up data. Subjects: Of 1096 cadaver organ donors harvested between 1 January 1979 and 28 February 1991, 484 had stored serum samples available for analysis. Recipients of organs from recombinant immunoblot assay (RIBA)–positive donors for whom adequate follow‐up was available were also included in the analysis. Measurements: Samples were tested for anti‐HCV by enzyme‐linked immunosorbent assay (ELISA). Confirmatory testing was done using a second‐generation RIBA. Hepatitis C viral RNA was detected in serum using the polymerase chain reaction. Liver biopsies were obtained from the organ donor and interpreted blindly by a pathologist unaware of the clinical data. Liver chemistry profiles and serum sample analysis for HCV RNA were done for transplant recipients. Results: From the 484 cadaver organ donors, 89 samples (18%; 95% CI, 15% to 21%) were reactive by ELISA. Of these, 33 (6.8%; CI, 4.6% to 9%) were RIBA seropositive. Hepatitis C viral RNA sequences were detected in 50% of the RIBA‐positive serum samples tested. Liver tissue was available from 24 of the 33 RIBA‐positive donors and showed chronic active hepatitis in 16, chronic persistent hepatitis in 2, and no abnormality in 6. Among the 46 recipients of a kidney from a RIBA‐positive donor, 13 (28%; CI, 15% to 41%) developed post‐transplant liver disease, of which only 4 cases were highly suggestive of viral transmission from the donor. Little morbidity and no mortality could be attributed to liver disease in this cohort of recipients. Conclusions: These data suggest that HCV transmission by organ transplantation is low and that the consequences of infection are small. If the medical condition of the potential recipient is so serious that other options no longer exist, the use of an organ from an anti‐HCV‐seropositive donor should be considered.