Hepititis C and renal transplantation: The controversy continues

Abstract

Hepatitis C virus (HCV) infection, the leading cause of posttransplant liver disease, has recently been recognized as one of the major causes of morbidity and mortality in renal transplantation. Most HCV antibody-positive recipients acquire HCV infection before or at the time of transplantation. The prevalence of HCV among patients with end-stage renal disease (ESRD) undergoing dialysis is reported between 12% to 85%, depending on the techniques used such as antibody and RNA assays [1‐ 4]. It has been shown that HCV is transmissible by organ transplantation [5, 6]. In recipients of kidneys from HCV antibody positive donors, 57 to 96% were tested positive for HCV RNA by polymerase chain reaction (PCR) and 0 to 55% developed post-transplantation liver disease [7]. There have been controversial reports on the long-term effects of HCV infection on graft and patient survival in kidney transplant recipients. In this issue of Kidney International, Pereira and colleagues analyze the impact of HCV infection on survival of kidney transplant and ESRD patients [8]. They report that the presence of HCV infection was associated with an increased risk of death in patients referred for renal transplantation, and the effect of transplantation was similar in anti-HCV positive and negative patients. They conclude that anti-HCV positive status is not a contraindication for renal transplantation, which has a beneficial effect on long-term survival in anti-HCV positive patients. The report by Pereira and associates provides new fuel to the controversy as to how HCV infection alters outcomes in ESRD and transplant population [8]. Two important infection-related outcomes are described by the authors: the relationship of infection to chronic liver disease and to transplant outcome. There have been other reports of progressive liver disease in HCVinfected renal allograft recipients. A study by Morales et al demonstrated that more than 50% of HCV positive renal transplant recipients exhibited a severe pattern including cirrhosis, chronic active hepatitis and chronic persistent hepatitis in liver biopsies indicating the seriousness of HCV infection [9]. Older age at transplant, female sex, and morphologic diagnosis of advanced chronic hepatitis were found to be associated with histologic progression to cirrhosis [10]. On the other hand, several other groups have described the absence of dire consequences of HCV infection on patient and graft survival in renal allograft recipients [11, 12]. A group of HCV-infected ESRD patients (N 5 14) was prospectively followed for up to two years with pretransplant liver biopsies, and virologic and biochemical parameters post-transplant [11]. All patients did well with functioning grafts despite enhanced viral replication and mild increase in liver enzymes. Haem and colleagues followed 62 HCV positive renal transplant recipients with liver biopsies for a mean of 72 months (range 36 to 108 months) [12]. Although they found a 42% incidence of chronic active hepatitis, patient and graft survival were not significantly different from HCV negative recipients. At our institution, we found that, despite a predisposition to post-transplant liver disease in recipients with pre-existing HCV infection, overall patient and graft survival were similar in long-term follow up (median follow-up 9 years) in the HCV positive and HCV negative recipients [12]. Irrespective of the antibody status, the outcome was poor in patients with associated liver disease. Less controversial has been the variant impact of HCV infection on patient outcomes related to forms of renal replacement. Similar to the report by Pereira et al, in a study by Knoll and colleagues, HCV-positive renal transplant recipients had a better survival compared with HCV-positive patients who were acceptable candidates for transplantation but were on dialysis [14]. The importance of these studies lies in using a cohort of dialysis patients for outcome comparison very similar to the transplant group as they were on the transplant waiting list, reducing the possibility that differences discerned were merely a consequence of selection bias. The continuing controversy of the impact of HCV infection on the transplant recipient demands further study and analysis by examining such issues as variant viral strains or geographic differences, and improving our understanding of HCV related liver disease. Nevertheless, the report by Pereira and his colleagues supports the conclusion that transplantation is the preferred mode of renal replacement therapy for HCV positive patients with end-stage renal disease [8].