Hepatitis C virus (HCV) infection is common among patients with end-stage renal disease (ESRD). However, the effect of HCV infection on survival among ESRD patients, and the impact of renal transplantation on the course of HCV infection has not been adequately defined. Sera from patients on the renal transplant waiting list at the New England Organ Bank between November 1986 and June 1990 were tested for anti-HCV using a third generation ELISA. All anti-HCV positive patients and a 1:1 ratio of randomly selected anti-HCV negative patients comprised the study sample. Duration of follow-up was calculated from the date of the first available serum specimen until death, loss to follow-up or December 31, 1995, whichever occurred earlier. Multivariate analysis of risk factors for mortality was performed using a Cox proportional hazards model which included anti-HCV as a time-independent (baseline) variable, transplantation as a time-dependent (follow-up) variable, and independently significant baseline covariates. Anti-HCV was detected in 287 (19%) of 1544 patients in whom sera were available, and 286 anti-HCV negative patients served as controls. Complete information was available in 496 (87%) of these 573 patients. Median follow-up was 73 months (range 1 to 110 months), during which time 302 (61%) patients underwent renal transplantation and 154 (31%) patients died. For anti-HCV positive patients compared to anti-HCV negative patients, the relative risk of death (and 95% confidence intervals) from all causes was 1.41 (1.01 to 1.97) and due to liver disease or infection was 2.39 (1.28 to 4.48). For patients who underwent transplantation compared to those who remained on dialysis, the relative risk of death from all causes between 0 to 3 months, 3 to 6 months, seven months to four years, and after four years was 4.75 (2.76 to 8.17), 1.76 (0.75 to 4.13), 0.31 (0.18 to 0.54) and 0.84 (0.51 to 1.37), respectively. There was no interaction between the effect of anti-HCV status as baseline and subsequent transplantation (P = 0.93), meaning that the association between treatment modality and survival was similar among anti-HCV positive and negative patients, at all intervals after transplantation. We conclude that HCV infection at the time of referral for transplantation is associated with an increased risk of death, irrespective of whether patients remain on dialysis or undergo transplantation. Transplantation has a beneficial rather than adverse effect on long-term survival in anti-HCV positive patients. Hence, anti-HCV positive status alone is not a contraindication for renal transplantation.
This two-part article discusses serologic testing of prospective donors for viral hepatitis B and C, as part of the comprehensive donor evaluation, and reviews the current policies and practices aimed at preventing donor-to-recipient transmission of hepatitis B and C viruses (HBV, HBC). This first part of the review discusses HBV. Organs procured from HBV-infected donors can transmit the virus to their recipients. Because infections with HBV have been associated with increased morbidity and mortality among renal transplant recipients, it is important to prevent HBV transmission with renal transplantation. Routine serologic evaluation of prospective organ donors for markers of HBV infection includes testing for hepatitis B surface antigen (HBsAg), anti-hepatitis B surface antigen antibody (HBsAb), and antibody to hepatitis B core antigen (anti-HBc). The risk of HBV transmission with kidney transplantation is a function of the serologic status of both donor and recipient. Knowledge of this risk is essential for the rational use of kidney allografts. HBsAg-positive donors are at high risk of transmitting HBV infection to their organ recipients, particularly if these donors are concurrently positive for hepatitis B e antigen (HBeAg). Kidneys from donors with isolated presence of HBsAb are unlikely to transmit HBV infection to their recipients. The risk of HBV transmission with the use of kidneys from IgG anti-HBc-positive, HBsAg-negative donors is low. Kidneys from donors negative for both HBcAg and anti-HBc are at low-to-negligible or no risk of transmitting HBV to their recipients. Under certain conditions, kidneys from HBV-infected donors can be safely used and thus prevent unnecessary discarding of organs. Kidneys from HBsAg-positive donors, who are negative for HBeAg, carry no risk or only minimal risk of transmitting HBV infection to their recipients if these recipients are immune to HBV or HBsAg-positive. However, the safety of these policies deserves further evaluation.
The results of this study suggest that the type and number of HCV genotypes may not have a significant impact on survival among ESRD patients.
The observations from this study indicate that: (1) in HD patients, there were no significant differences in cytokine synthesis by PBMC drawn before the three different dialysis treatments during the week; (2) there is a close relationship between IL-1Ra synthesis from PBMC cultured under different stimulatory conditions; (3) the secreted levels of IL-1Ra correlate directly with total synthesis (cell-associated and secreted); (4) with the exception of duration of dialysis, none of the other clinical or laboratory parameters correlated with cytokine synthesis; and (5) the diminished endotoxin- or IgG-stimulated IL-1Ra synthesis with increasing time on dialysis is possibly another sign of the impaired host-defense system in patients on long-term hemodialysis.
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