Results of Liver Transplantation From Old Donors

K. Dudek*, O. Kornasiewicz, P. Remiszewski, K. Zieniewicz, T. Wróblewski, and M. Krawczyk

Department of General, Transplant and Liver Surgery Medical University of Warsaw, Warsaw, Poland

0041-1345/1http://dx.doi

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ABSTRACT

Introduction. Faced with a shortage of organs for liver transplantation, the use of graftsfrom older donors is justified. However, there remains little consensus on how this useimpacts the graft and patient outcomes after transplantation from these older donors. Theaim of the present analysis was to assess the graft and patient outcomes after liver trans-plantation from deceased donors >60 years of age.Methods. From January 2007 to January 2011, 505 subjects were identified as liver graftdonors after brain death, of which 7.35% were �60. To determine the effect of donor ageon graft and patient outcomes, we analyzed donor age, recipient age, the Model for End-State Liver Disease (MELD) score of recipients at the time of transplantation, earlyposttransplant complications, and mortality.Results. The posttransplant follow-up was 29 � 25.5 months, and 3-year patient mortalityfrom donors, grouped according to age, was 7.92% with donors <30; 15.78% with donors30e50, 10.68% with donors 50e60, and 12.50% with donors >60. After analysis of patientand graft survival based on donor graft age, 3-year patient survival according donor agewas 89.29% with donors <30, 83.85% with donors 30e50, 89.89% with donors 50e60, and87.50% with donors >60. Analysis showed overall patient and graft survival rates fromolder donors were not worse than those from younger donors (P > .1). Among the cases,3-year patient survival according to MELD score was 91.19% with a MELD of I, 85.37%with a MELD of II, and 67.67% with a MELD of III; differences in graft and patientsurvival when comparing low MELD I and high MELD III were significantly different(P < .01).Conclusions. A more advanced age of a donor should not be a contraindication for livertransplantation. The present analysis shows that liver grafts from donors >60 can be usedsafely in older recipients who presented with relatively low MELD scores. Analyses alsoindicate that high MELD obtained before transplantation may be an important prognosticfactor for graft and patient survival.

*Address correspondence to Krzysztof Dudek, Department ofGeneral, Transplant and Liver Surgery, Medical University ofWarsaw Banacha 1a, 02-097 Warsaw, Poland. E-mail:krzysztofdudek@o2.pl

OVER the last decade, a growing number of advanced-age recipients and organ shortages have caused a

steady increase in liver transplantation from older donors.A shortage of deceased donors remains among the mainfactors that significantly limits the increasing number of liverharvesting taking place in Eastern Europe. In Poland from1999 to 2005, older donors were considered to be worsecandidates than younger donors, and they were excludedfrom organ harvesting or regarded as “marginal donors.”Since 2006, we have changed our policies and older donorshave become an alternative to overcome the shortage oforgans. Based on our experience, transplant patients who

4.org/10.1016/j.transproceed.2014.09.022

have received “marginal organs” from older donors hadsimilar initial graft function parameters as patients whoreceived organs from younger donors; therefore, we haveaccepted older donors in routine procedures. The Model forEnd-Stage Liver Disease (MELD) was introduced in Polandin 2005. Since then, it has remained the main selection

ª 2014 Published by Elsevier Inc.360 Park Avenue South, New York, NY 10010-1710

Transplantation Proceedings, 46, 2762e2765 (2014)

Table 2. Comparison and Matching of Donor and Recipient byAge Groups

Characteristic

Age Group (y)

<30 30e50 51e60 >60

LIVER TRANSPLANTATION FROM OLD DONORS 2763

criterion for patients waiting for liver transplantation in ourdepartment. The aim of present analysis is to assess the graftand patient outcomes after liver transplantation fromdeceased donors >60 years old in relation to MELD score.

AgeMean donor age (y) 22.24 40.9 54.97 64.06Mean recipient age (y) 43.6 44.42 47.46 49.41P .15 .18 .28 .12

GenderDonor gender (men/women) 58/43 79/92 52/79 13/19Recipient gender (men/women) 45/56 83/88 62/69 18/16P .14 .32 .98 .41

BMIMean donor BMI 22.24 27.08 28.31 26.31Mean recipient BMI 25.66 28.52 29.46 25.98P .21 .45 .34 .18

Abbreviation: BMI, body mass index.

MATERIAL AND METHODS

From January 2007 to January 2011, 505 subjects were identified aswhole liver graft donors after brain death, of which 435 wereincluded in the analysis. Among them 23.21% were <30 years,39.30% were between 30 and 50 years, 30.11% were between 50 and60 years, and 7.35% were >60 years old.

Liver transplantations were performed using the piggybacktechnique without venovenous bypass. The 3-year patient survivalwas the primary endpoint for this study, and was calculated ac-cording to the date of transplantation, patient death, retrans-plantation, or last investigation.

Retransplantations were excluded from the analysis of patientsurvival. Patients were divided according to donor age and MELD.The characteristics of patients and donors are shown in Table 1.The donor and recipient breakdown according to gender and bodymass index is shown in Table 2, with no differences between groups(P > .05) using analysis of variance. MELD classification of donorsis shown in Table 3. The standard MELD estimation was calculatedas follows:

MELD ¼ ð3:8 � ln½serum bilirubin ðmg=dLÞ�Þþ ð11:2 � ln½INR�Þþ ð9:6 � ln½serum creatinine ðmg=dLÞ�Þ:

The Kaplan-Meier method was used to illustrate survival withingroups. To obtain patient and graft survival estimators, Kaplan-Maier table analysis was performed using STATISTICA version9.1. The graft and patient survival were calculated within a 1- to 48-month period. We included the following factors in our analysis:Donor age, recipient age, MELD of recipients at the time oftransplantation, earlier complications, and mortality. In our statis-tical analysis, we specifically compared the following agegroups: <30 versus 30e50 years, <30 versus 50e60 years, and <30versus >60 years using a log-rank test (threshold of P value <.05).

RESULTS

The median time posttransplant follow-up was 29 � 25.5months, and 3-year patient mortality from donors groupedaccording to age was 7.92% with a donor <30, 15.78% with

Table 1. Characteristics of the Donor and Recipient of 435 Co

Characteristic

Don

<30 30e50

Patients, n (%) 101 (23.21) 171 (39.30)Recipients age (y) 43.6 � 14.37 44.42 � 12.72Donor age (y) 22.24 � 4.5 40.9 � 6.28Cold ischemia time (min) 527 � 110 538 � 115MELD score 15.6 � 8.3 18.2 � 11.2Deaths, n (%) 9 (8.91) 26 (15.20)Retransplantation, n (%) 3 (2.97) 3 (1.75)

Abbreviation: MELD, Model for End-Stage Liver Disease.Values are given as mean values � standard deviation unless otherwise noted.

a donor 30e50, 10.68% with a donor 50e60, and 12.50%with a donor >60 years old. After analysis of patient andgraft survival by donor graft age, the 3-year patient survivalaccording donor age was: 89.29% with a donor <30, 83.85%with a donor 30e50, 89.89% with a donor 50e60, and87.50% with a donor >60 years old (Fig 1B). Statisticalanalyses showed overall patient and graft survival rates fromolder donors were not significantly worse than those fromyounger donors (P > .1). Among the cases, 3-year patientsurvival according to MELD was the following: 91.19% forMELD I, 85.37% for MELD II, and 67.67% MELD III (Fig2B); differences in graft and patient survival whencomparing low MELD I and high MELD III were signifi-cant (P < .01; Fig 2).

DISCUSSION

At present, liver transplantation from older donors is theonly strategy available to increase the number of trans-planted organs and thus shorten the waiting time fortransplant recipients. The discussion regarding the risk ofthis type of organ transplantation has been pursued formany years, both at the biochemical and histopathologiclevels, as well as through the long-term experiences of pa-tients. Many factors directly influence the results of trans-plantation, and one of the most important is the quality of

mplete Liver Transplantations After Brain Death of Donor

or Age (y)

Total51e60 >60

131 (30.11) 32 (7.35) 435 (100)47.46 � 10.86 49.41 � 9.19 44.71 � 13.0654.97 � 2.71 64.06 � 2.73 41.52 � 14.1529 � 117 581 � 110 535 � 11417.5 � 11.4 19.6 � 11.78 d

15 (11.45) 4 (12.5) 54 (12.41)7 (5.34) 3 (9.37) 16 (3.67)

Table 3. Comparison and Matching of Donor and RecipientBased on Model for End-Stage Liver Disease (MELD) Score

MELD Score

Age Group (y), n (%)

<30 30e50 51e60 >60

<20 77 (76.23) 121 (70.76) 94 (71.75) 16 (50.00)20e29 15 (14.85) 18 (10.25) 18 (13.74) 10 (31.25)>29 9 (8.91) 32 (18.73) 19 (14.50) 6 (18.75)

2764 DUDEK, KORNASIEWICZ, REMISZEWSKI ET AL

the implanted organ. The common view that organs ob-tained from younger donors are of a much higher qualitythan those from older donors lingers in many transplantcenters, leading to a reduced overall number of organs usedfor transplantation. Based on this general concept, livertransplantation from older donors may entail several prob-lems. One of them is a limited functional reserve of hepa-tocytes. On the other hand, liver transplantation from olderdonors should be possible because of the great regenerativepotential of hepatocytes [1].Each year, there are a growing number of deceased

donors in Poland, but the gap between organ supply anddemand continues to increase. In Western and SouthernEurope, a limited number of potential deceased donorshave resulted in an increased number of recipients onwaiting lists for liver transplantation. This has led to graftacceptance from older and “marginal” donors [2]. In manyliver transplantation departments, nonstandard liver donors(>60 years old) comprise almost one half of the totalnumber of cadaveric donors [3,4]. In many transplant cen-ters, marginal grafts are given to marginal recipients [5].Since its introduction and acceptance in 2002 by The

Organ Procurement and Transplantation Network (OPTN),the MELD system has become among the most valuableindicators of survival after liver transplantation. Parametersof donors based on the age of patients, sodium concentra-tion, transaminase levels, and hemodynamic instabilitydirectly segregated organs as good and acceptable for

Fig 1. Kaplan-Meier plots of (A) graft survival and (B) patient survivaplant. No significant differences were observed.

transplantation and others as marginal, that is, only to beused when an immediate threat to the recipient’s life waspresent.Presently, in many liver transplant centers, nonstandard

organ transplantation to high MELD recipients is routine.This group of patients, with multiple disorders and highdecompensation, is considered to be very high risk [6].When comparing standard and nonstandard liver donors,the risk of death after liver transplantation can be easilyestimated based on the MELD score [7]. Many studies havealso shown a correlation between older donor age and moresevere recurrences of hepatitis C in recipients [8].Authors presenting outcomes of liver transplantation in a

group of living donor liver transplant recipients concludedthat grafts from older living donors can be safely used, withcaution given to other risk factors such as a marginal graftvolume or severe recipient conditions. The recipient age didnot affect the outcome of living donor liver transplantationswhen patients with a low MELD score (<20) received graftsfrom consanguineous donors [9,10]. Nevertheless, the au-thors suggest worse long-term results and survival, and anincreased risk of postoperative complications in patientswith high preoperative MELD scores in those whom mar-ginal organs were transplanted, indicating a significant in-crease of risk in this type of combination [11].No significant differences were found in the survival of

transplant recipients based donor age, which directly impliesthat the use of these organs is reasonable and safe. Ourfindings show that an important factor on patient survival isthe selection of donors and recipients according to the de-gree of liver failure based on preoperative MELD scores.Owing to worse long-term results, it seems advisable totransplant organs from younger donors (<30 years of age)rather than from donors >60 years of age into patients withhigh MELD score (>29).In conclusion, advanced donor age is not a contraindi-

cation to liver transplantation, and liver grafts from donors

l according to donor age groups from 0 to 48 months posttrans-

Fig 2. Kaplan-Meier plots of (A) graft survival and patient survival (B) according to Model for End-Stage Liver Disease (MELD) groupsfrom 0 to 48 months posttransplant. Results suggest that high preoperative MELD scores may lead to decreased 3-year graft andpatient survival.

LIVER TRANSPLANTATION FROM OLD DONORS 2765

>60 years of age can be safely used in older recipients with arelatively low risk. However, in patients with high preoper-ative MELD scores, liver transplantation from older donorsmay be an important prognostic factor for both graft andpatient survival. Therefore, the preoperative MELD indexshould be included in the eligibility of patients for trans-plantation of organs procured from older donors.

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