Use of Octogenarian Donors for Liver Transplantation: A Survival Analysis

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http://onlinelibrary.wiley.com/doi/10.1111/ajt.12843/abstract

Use of Octogenarian Donors for Liver Transplantation: A Survival Analysis
D. Ghinolfi1,*, J. Marti2, P. De Simone1, Q. Lai1, D. Pezzati1, L. Coletti1, D. Tartaglia1, G. Catalano1, G. Tincani1, P. Carrai1, D. Campani3, M. Miccoli4, G. Biancofiore5 andF. Filipponi1
DOI: 10.1111/ajt.12843
American Journal of Transplantation
Volume 14, Issue 9, pages 2062–2071, September 2014

Abstract
Use of very old donors in liver transplantation (LT) is controversial because advanced donor age is associated with a higher risk for graft dysfunction and worse long-term results, especially for hepatitis C virus (HCV)-positive recipients. This was a retrospective, single-center review of primary, ABO-compatible LT performed between 2001 and 2010. Recipients were stratified in four groups based on donor age (<60 years; 60–69 years; 70–79 years and ≥80 years) and their outcomes were compared. A total of 842 patients were included: 348 (41.3%) with donors <60 years; 176 (20.9%) with donors 60–69 years; 233 (27.7%) with donors 70–79 years and 85 (10.1%) with donors ≥80 years. There was no difference across groups in terms of early (≤30 days) graft loss, and graft survival at 1 and 5 years was 90.5% and 78.6% for grafts <60 years; 88.6% and 81.3% for grafts 60–69 years; 87.6% and 75.1% for grafts 70–79 years and 84.7% and 77.1% for grafts ≥80 years (p = 0.065). In the group ≥80 years, the 5-year graft survival was lower for HCV-positive versus HCV-negative recipients (62.4% vs. 85.6%, p = 0.034). Based on our experience, grafts from donors ≥80 years may provide favorable results but require appropriate selection and allocation policies.

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http://onlinelibrary.wiley.com/doi/10.1111/ajt.13068/full

Liver Transplantation With Aged Donors in Patients With Hepatitis C Virus
M. Gastaca*, P. Prieto, A. Valdivieso andJ. Ortiz de Urbina
DOI: 10.1111/ajt.13068
American Journal of Transplantation
Early View (Online Version of Record published before inclusion in an issue)

To the Editor
We read with great interest the study by Ghinolfi et al [1] recently published in American Journal of Transplantation. In this report, 5-year patient and graft survival rates with donors ≥80 years were outstanding—78.2% and 77.1%, respectively. Hepatitis C virus (HCV) status was the most significant factor of graft survival at multivariate analysis (hazard ratio 1.749, p < 0.001). At the latest follow-up, clinically significant HCV recurrence was observed in 13.6% and 9% of the patients transplanted with donors between 70 and 79 years of age and ≥80 years, respectively; comparable to that observed with younger donors. Of note, 5-year graft survival of the HCV-positive recipients transplanted with donors ≥80 years was 62.4% which, albeit significantly lower than that of the non-HCV recipients, is surprisingly high. Unfortunately, information on late graft loss and late retransplantation is not provided by the authors.

Our experience is different. In November 2009, our IRB approved a retrospective case–control study to compare a study group of 25 HCV-positive patients transplanted between January 1998 and October 2004 with donors ≥70 years with a control group of 50 patients transplanted with donors <70 years during the same period of time [2]. All recipients had a minimum follow-up of 5 years. An aggressive HCV recurrence, defined as cholestatic or fibrosis stage ≥2 according to Scheuer score within the first year, was assessed in 75% of patients in the study group versus 33.3% in the control group (p = 0.002). Survival at 1, 5, 7, and 10 years in the study and control groups was as follows: graft survival was 84%, 48%, 29.1%, and 29.1% versus 100%, 82%, 74%, and 57%, respectively (p < 0.008), while patient survival was 84%, 63.7%, 51.8%, and 51.8% versus 100%, 82%, 74%, and 62.8%, respectively (p = n.s.). Of note, the rate of retransplantation was 25% versus 2% in the study and control groups (p = 0.004), all due to HCV recurrence. Similar results were recently published with 50% and 40% 5-year patient and graft survival in HCV-positive recipients transplanted with donors older than 70 years [3].

The reasons for the positive results obtained by Ghinolfi et al are difficult to determine. The mean Model for End-Stage Liver Disease score of our study group was 15 ± 6.4 and our aged donors were also carefully selected with significantly less hypotension episodes, lower mean alanine aminotransferase and a mean cold ischemic time of 290 ± 65 min. Nevertheless, the fact that our patients were transplanted in an earlier period of time and the inclusion of HCV recipients with preemptive antiviral treatment in their study might account for the relative superiority of their results.

For the last decade, our policy has been to avoid the use of older donors in patients with HCV owing to a prohibitively high rate of recurrence leading to graft loss and retransplantation; however, this policy will have to be revised in the near future when the new, highly effective, HCV antiviral therapies become widely available [4].

M. Gastaca*, P. Prieto, A. Valdivieso, J. Ortiz de Urbina
Hepatobiliary Surgery and Liver Transplantation Unit, Cruces University Hospital, University of the Basque Country, Baracaldo, Spain

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http://onlinelibrary.wiley.com/doi/10.1111/ajt.13077/full

Liver Transplantation With Aged Donors in Patients With Hepatitis C Virus: Authors' Reply
D. Ghinolfi*, Q. Lai, P. De Simone, D. Pezzati andF. Filipponi
DOI: 10.1111/ajt.13077
American Journal of Transplantation
Early View (Online Version of Record published before inclusion in an issue)

To the Editor:
We wish to thank Gastaca et al for their comments [1] on our experience with octogenarian donors in liver transplantation (LT) [2]. Although the introduction of direct antiviral agents and the upcoming interferon-free drug schedules will affect the global scenario of LT for hepatitis C virus (HCV) by curtailing posttransplant HCV recurrence rates, improving graft and patient survival, and reshaping current allocation policies, some issues addressed by Gastaca et al [1] require clarification.

Similarly to what was reported by Gastaca et al [1], in our experience, donor age was a major risk factor for graft loss in HCV-positive recipients. The difference in 5-year graft survival mentioned by the Spanish colleagues [3] is more superficial than real, due to the fact that the two series are not entirely comparable [2, 3]. The Spanish authors reported the results of a case–control, retrospective series, including a small number of HCV-positive patients transplanted in earlier eras (1998–2004) with donor grafts ≥70 years (n = 25) versus <70 years (n = 50) [3]. They adopted a case–control methodology, a different definition of “severe” HCV recurrence of the liver graft, and presumably different immunosuppressive regimens (as per drug type and level of immunosuppression). Our recipients were concentrated in later times, when knowledge gained from previous experiences, insight into the mechanisms of HCV recurrence in general and fibrosing cholestatic hepatitis in particular, a shift from high-dose to minimized immunosuppressive regimens and a more aggressive policy of HCV treatment posttransplantation, might all account for the gap across the two studies. Furthermore, despite the ominous impact of HCV status on LT outcome, we have deliberately declined retransplantation to patients with posttransplant HCV recurrence, due to a persistently high donor age throughout the entire study period [2]. Graft survival in HCV-positive patients was therefore censored at time of death or latest follow-up, and aggressive treatment modalities and supportive measures in use at our center might also explain the apparent differences between our series [4].

Consistent with our experience, the Spanish authors used elderly grafts for low-risk recipients as per the Model for End-Stage Liver Disease (MELD) scores. However, their mean MELD values are higher than in our experience, and in order to get more insight, a direct comparison should be performed between the individual MELD scores of failing HCV recipients in both series. Recent evidence from a multicenter Italian study showed a direct correlation between donor age and recipient MELD scores, and HCV-positive patients with MELD scores ≥20 receiving grafts from donors 80–89 years old showed 5-year patient survival rates similar to the Spanish experience (44% vs. 48%, respectively) [5].

We strongly believe that elderly donors play a pivotal role in expanding the current donor pool, and every effort should be made to better identify patients who could benefit the most from such a resource. Comparisons across retrospective series are important, but are limited by differences in study methodologies and patterns of clinical practice. Hopefully, HCV LT recipients are about to enter a new era and achieve similar results as other categories of patients.

D. Ghinolfi*, Q. Lai, P. De Simone, D. Pezzati and F. Filipponi