Abstract. Kidneys from donors who are positive for hepatitis C virus (DHCVϩ) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001 followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCVϩ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P Ͻ 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCVϩ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCVϩ, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCVϩ was independently associated with mortality in each subgroup. It is concluded that DHCVϩ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCVϩ organs should be considered at high risk for excessive immunosuppression.The expected clinical course of hepatitis C infection as it affects organ transplant recipients, as well as the use and effect of kidneys from donors who are positive for hepatitis C, remain controversial topics in renal transplantation. Recently published data confirmed that kidneys from donors who were hepatitis C positive (HCVϩ) were associated with an independently increased risk of death in renal transplant recipients regardless of recipient HCV status (1). However, donor hepatitis C seropositivity (DHCVϩ) was not independently associated with mortality when limited to patients with valid information (Centers for Medicare and Medicaid Studies [CMS] Form 2728) on comorbid conditions at the time of dialysis initiation. This may have been because of the relatively small numbers of transplant recipients for whom complete data were available during the study period or because cardiovascular comorbidity was actually lower in patients who received DHCVϩ kidneys, yet the mortality risk for recipients of DHCVϩ kidneys was still greater than for patients who received DHCVϪ kidneys. Possibly, recipients of DHCVϩ kidneys were sicker to start with and thus had a higher risk of death unrelated to receiving a DHCVϩ kidney. Since that study, there have been substantial changes in maintenance immunosuppression practices in the United States. In particular, recent reports have confirmed tha...

Abstract. The impact of hepatitis C virus-positive donor kidneys on patient survival has not been analyzed in a national study. This study analyzed 20,111 adult (age, Ն16 yr) recipients having solitary cadaveric kidney transplants from adult donors with valid donor hepatitis C serologies from

Abstract. Complications associated with use of donor hepatitis C-positive kidneys (DHCVϩ) have been attributed primarily to posttransplantation liver disease (as a result of hepatitis C disease). The role of posttransplantation diabetes has not been explored in this setting. With the use of the United States Renal Data System database, 28,942 Medicare KT recipients were studied from January 1, 1996, through July 31, 2000. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (AHR) for the association of sero-pairs for HCV (Dϩ/RϪ, Dϩ/Rϩ, DϪ/Rϩ and DϪ/RϪ) with Medicare claims for de novo posttransplantation HCV and posttransplantation diabetes. The peak risk for posttransplantation HCV was in the first 6 mo after transplantation. The incidence of posttransplantation HCV after transplantation was 9.1% in Dϩ/RϪ, 6.3% in Dϩ/Rϩ, 2.4% in DϪ/Rϩ, and 0.2% in DϪ/RϪ. The incidence of posttransplantation diabetes after transplantation also peaked early and was 43.8% in Dϩ/RϪ, 46.6% in Dϩ/Rϩ, 32.3% in DϪ/Rϩ, and 25.4% in DϪ/RϪ. Associations for both complications were significant in adjusted analysis (Cox regression). Both posttransplantation HCV (AHR, 3.36; 95% confidence interval, 2.44 to 4.61) and posttransplantation diabetes (AHR, 1.81; 95% confidence interval, 1.54 to 2.11) were independently associated with an increased risk of death, but posttransplantation diabetes accounted for more years of life lost, particularly among recipients of DHCVϩ kidneys. Posttransplantation diabetes may contribute substantially to the increased risk of death associated with use of DHCVϩ kidneys and accounts for more years of life lost than posttransplantation HCV. Because HCV infection acquired after transplantation is so difficult to treat, methods that have been shown to reduce viral transmission warrant renewed attention.

Despite advances in the therapy of chronic hepatitis C, a large number of patients do not respond to current therapies. The study objective was to assess whether a combination of interferon (IFN) alfacon-1 and ribavirin improves the response rate compared with a combination of INF alpha-2b and ribavirin in chronic hepatitis C subjects. The study was designed as an open-label, prospective, randomized, controlled study; 128 subjects with chronic hepatitis C were randomized to INF alfacon-1, 15 microg three times per week, plus ribavirin, 1 g/day, or IFN-alpha2b, 3 million units three times per week, plus ribavirin, 1 g/day for 48 weeks. The end point of the study was a sustained viral response, defined as undetectable HCV RNA at 24 weeks post 48 weeks of treatment. Overall, 57% of subjects in the INF alfacon-1/ribavirin group achieved a sustained antiviral response, compared with 40% of subjects in the IFN-alpha2b/ribavirin group (P = 0.052). In the subset of subjects with a high viral load, HCV RNA was successfully eradicated in more individuals who received INF alfacon-1/ribavirin than subjects who received IFN-alpha2b/ribavirin (57 versus 31%; P = 0.025). Among individuals with genotype 1 and a high viral load, the sustained antiviral response was significantly higher with INF alfacon-1/ribavirin than with IFN-alpha2b/ribavirin (46 versus 14%; P = 0.019). Adverse events were similar in both treatment groups. In conclusion, this study demonstrated that the combination of INF alfacon-1 and ribavirin provides a significantly better treatment response compared with the combination of IFN-alpha2b and ribavirin in chronic HCV subjects infected with genotype 1 and a high viral RNA load.