Hepatitis C and Renal Transplantation in the Era of Modern Immunosuppression

Abstract

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...

The Impact of Transplantation with Deceased Donor Hepatitis C-Positive Kidneys on Survival in Wait-Listed Long-term Dialysis Patients

“…Transplantation of kidneys from deceased donors who are antibody positive for hepatitis C virus (DHCV+) is associated with greater recipient mortality than occurs with kidneys transplanted from deceased donors who are antibody negative for hepatitis C virus (DHCV−) (1,2). While use of DHCV+ kidneys for recipients who are themselves hepatitis C antibody positive (HCV+) is associated with an increased risk in late mortality compared to use of DHCV− kidneys (2,3), no previous analyses have compared survival after transplantation of DHCV+ kidneys with survival of wait-listed patients who remain on dialysis.…”

“…While use of DHCV+ kidneys for recipients who are themselves hepatitis C antibody positive (HCV+) is associated with an increased risk in late mortality compared to use of DHCV− kidneys (2,3), no previous analyses have compared survival after transplantation of DHCV+ kidneys with survival of wait-listed patients who remain on dialysis.…”

“…More than half of DHCV+ kidneys are transplanted in HCV+ recipients in the United States; risk factors associated with DHCV+ kidney transplantation include advanced donor and recipient age, African American race, and the possibility of a high rate of dialysis access complications (1,2,4). In addition, DHCV+ kidneys may be used with substantial variation between or within transplant centers depending on circumstances impossible to capture in reviewing single-or multi-center experiences.…”

Hepatitis C Virus Infection in Chronic Kidney Disease

“…Any decision in this regard must be balanced against data suggesting that uninfected patients that receive HCV-positive kidneys have increased mortality. 77 Furthermore, the ethics of knowingly infecting a patient with HCV must be carefully weighed against the knowledge that not all patients achieve an SVR with DAA treatment, and there is no certainty that payers will approve this costly therapy after transplantation. Any discussion of knowingly infecting a patient with HCV at the time of transplant must be with full understanding of the accompanying risk of fibrosing cholestatic hepatitis, an aggressive form of HCV seen after liver transplantation or KT during the period of maximal immunosuppression.…”

Untitled

“…1 The prevalence of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) and in kidney transplant recipients is significantly higher than in the general population, 2,3 and it is associated with increased morbidity and mortality. 3 The United States Renal Data System (USRDS) analysis of 36 956 patients between 1996 and 2001 demonstrated a 6.8% prevalence of HCV infection 4 among kidney transplant recipients.…”