Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients

Abstract

Recurrent hepatitis occurs in the majority of patients undergoing liver transplantation for hepatitis C virus (HCV) cirrhosis, with progression to cirrhosis in up to 30% after 5 years. Based on these data, a decrease in survival can be anticipated with prolonged follow-up. Furthermore, posttransplantation HCV-fibrosis progression has been shown in recent years to increase. Our aims were (1) to describe the natural history of HCV-infected recipients, particularly to determine whether survival has decreased in recent years; (2) to compare this outcome with that observed in non-HCV-infected cirrhosis controls; and (3) to determine the factors associated with disease severity and survival. Among 522 cirrhotic patients undergoing transplantation between 1991 and 2000, 283 (54%) were infected with HCV. Yearly biopsies were performed in these recipients and at 1 and 5 years in the remainder. With similar follow-up, the percentage of deaths in the HCV(؉) group was significantly higher than in the HCV(؊) group (37% vs. 22%, P < .001), and patient survival was lower (77%, 61%, 55% vs. 87%, 76%, 70% at 1, 5, and 7 years, respectively; P ‫؍‬ .0001). Although survival has increased in the HCV(؊) group in recent years, it has significantly decreased in HCV recipients (P < .0001). The main cause of death among the latter was decompensated graft cirrhosis (n ‫؍‬ 23/105, 22%), whereas that of HCV(؊) patients was infections (n ‫؍‬ 10/52, 19%). Reasons for the recent worse outcome in HCV(؉) recipients include the increased donor age and stronger immunosuppression. In conclusion, patient survival is lower among HCV(؉) recipients than among HCV(؊) ones and has been decreasing in recent years. The aging of donors is a major contributor to this worse outcome. (HEPATOLOGY 2002;36:202-210.) H epatitis C virus (HCV)-cirrhosis is the most frequent diagnosis in patients undergoing liver transplantation. 1 Viral recurrence is universal, 2 with development of histologic hepatitis in the majority of patients 3,4 and progression to cirrhosis in up to 30% after 5 years. 5,6 To date, however, most series have revealed no differences in patient or graft survival compared with uninfected controls. [3][4][5]7 Various reasons may explain these supposed discrepancies, one of which is the existence of different end points when assessing the effect of HCV infection on the graft. An indirect way to assess this effect is by calculating the rate of histologic progression posttransplantation, a task easily performed in the posttransplant setting because of the multiple biopsies generally performed and, through assessment of this rate, estimating the median time to development of graft cirrhosis. In one study, this duration was estimated to be 12 years, a duration significantly shorter than that described for the immunocompetent population. 6 From these data, one can anticipate an increase in HCV-related graft loss in the near future as transplant programs reach their second decade of activity. Our center follows a strict policy of performing annual li...

12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus

“…[14][15][16][17][18] Only 3 trials have enrolled over 100 patients per arm. [19][20][21] The observational study of 283 HCV-positive liver transplant recipients by Berenguer and colleagues showed that use of tacrolimus compared to CsA-ME was independently associated with development of cirrhosis by multivariate analysis (P ϭ 0.009). 19 Ghobrial et al reported a shorter time to HCV recurrence with tacrolimus, 20 while other researchers have identified a trend suggesting that immunosuppressive treatment with tacrolimus could promote the early induction of fibrosis.…”

Impact of donor age on survival and fibrosis progression in patients with hepatitis C undergoing liver transplantation using HCV+ allografts

“…Through randomized, blinded fashion we matched each case with its corresponding control based on specific characteristics that previous studies have demonstrated to most likely influence clinical outcomes. 18,21 In order of importance, these variables included donor age (within 10 yr), year of transplantation (within 4 yr), United Network for Organ Sharing/Model for End-Stage Liver Disease score, and recipient age (within 20 yr). Donor age has shown to impact survival after liver transplantation in HCV and thus was chosen as a matching variable.…”

“…More recently, donor age Ն50 yr has specifically been found to have a negative impact on both patient and graft survival as well as accelerating fibrosis progression and the progression to cirrhosis. [16][17][18] There have been no studies to date examining the impact of donor age on liver transplantation using HCVϩ donor livers.…”

Hepatitis C treatment before and after liver transplant

“…Donor age seems to influence graft survival only in HCVpositive patients. However, there is little chance that this will change, since very few transplant programs are able to pair younger donors with HCV-positive receptors [11,12].…”