Similar liver transplantation survival with selected cardiac death donors and brain death donors

Authors


Abstract

Background:

The outcome of orthotopic liver transplantation (OLT) with controlled graft donation after cardiac death (DCD) is usually inferior to that with graft donation after brain death (DBD). This study compared outcomes from OLT with DBD versus controlled DCD donors with predefined restrictive acceptance criteria.

Methods:

All adult recipients in the Netherlands in 2001–2006 with full-size OLT from DCD (n = 55) and DBD (n = 471) donors were included. Kaplan–Meier, log rank and Cox regression analyses were used.

Results:

One- and 3-year patient survival rates were similar for DCD (85 and 80 per cent) and DBD (86·3 and 80·8 per cent) transplants (P = 0·763), as were graft survival rates (74 and 68 per cent versus 80·4 and 74·5 per cent; P = 0·212). The 3-year cumulative percentage of surviving grafts developing non-anastomotic biliary strictures was 31 per cent after DCD and 9·7 per cent after DBD transplantation (P < 0·001). The retransplantation rate was similar overall (P = 0·081), but that for biliary stricture was higher in the DCD group (P < 0·001). Risk factors for 1-year graft loss after DBD OLT were transplant centre, recipient warm ischaemia time and donor with severe head trauma. After DCD OLT they were transplant centre, donor warm ischaemia time and cold ischaemia time. DCD graft was a risk factor for non-anastomotic biliary stricture.

Conclusion:

OLT using controlled DCD grafts and restrictive criteria can result in patient and graft survival rates similar to those of DBD OLT, despite a higher risk of biliary stricture. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Introduction

In orthotopic liver transplantation (OLT) increasing waiting list mortality owing to organ shortage has led to the use of extended criteria donors. It is believed that liver grafts from extended criteria donors with, for instance, older age, donation after cardiac death (DCD), split or partial grafts and steatosis carry a higher risk of primary non-function1–4. DCD is divided into controlled (category III, awaiting cardiac arrest; category IV, cardiac arrest after brainstem death) and uncontrolled (category I, brought in dead; category II, unsuccessfully resuscitated; category V, cardiac arrest in admitted patient)5. Results of OLT in uncontrolled DCD have been below average. Results from controlled DCD, however, are encouraging, although most centres report graft survival rates below that of OLT with donation after brain death (DBD) liver grafts. This is mostly owing to a higher retransplantation rate because of an increased rate of primary non-function, vascular complications and non-anastomotic biliary stricture5–10. Similar patient survival after DCD and DBD OLT has been reported recently from an experienced centre11.

In the Netherlands there has been a widening of the gap between numbers of donors and recipients, resulting in a 15 per cent mortality rate on the waiting list in 2000. In 2001, therefore, OLT with controlled DCD donor grafts was introduced within a national protocol for multiorgan donation. These liver grafts were allocated according to the national waiting list and with very strict criteria for graft acceptance. This paper reports the outcome, and risk factors for graft loss and biliary stricture, in OLT with DCD and DBD liver grafts in the Netherlands between 2001 and 2006.

Methods

All adult recipients in the Netherlands undergoing full-size OLT from DCD and DBD donors between 1 January 2001 and 31 December 2006 were enrolled. Recipients younger than 18 years, procedures with a reused graft (previously used as auxiliary graft12), OLTs after living donation, split transplants and auxiliary liver transplants were excluded. Follow-up was until 1 January 2009.

Protocol for accepting recovered organs from donation after cardiac death donors

In September 2001 a national protocol was introduced for multiorgan donation of organs recovered from DCD donors. No DCD donors were accepted before 2001. The national protocol was designed for the procurement of kidneys, liver, pancreas and lungs from controlled, category III donors. The protocol included restrictive criteria for accepting organs after DCD (Table1) and exclusion criteria. A description was also included of the surgical procedure for rapid recovery of the abdominal and thoracic organs by a midline laparotomy and sternotomy, followed by open cannulation of the distal aorta and pulmonary artery. Decompression of the venous system was performed by insertion of a decompression tube into the abdominal caval vein or by cutting the caval vein at the level of the right atrium. The isolated abdominal organs were perfused with either histidine–tryptophan–ketoglutarate (HTK) or University of Wisconsin (UW) solution, both containing 20 000 units heparin. Heparin was not administered before the start of the procedure.

Table 1. Criteria for accepting a donor after cardiac death in the Dutch national protocol
DCD inclusion criteria 
  1. DCD, donation after cardiac death; MAP, mean arterial pressure.

Maastricht category5III
Donor warm ischaemia time (min)< 30
Age (years)1–55
Body mass index (kg/m2)< 28
Hypotensive periods (MAP < 50 mmHg) (min)< 15

When a potential DCD donor was identified and the family had been informed about his or her irreversible fatal condition, permission to withdraw medical support was sought. On agreement of the family, a transplantation coordinator was contacted, whose role was to provide support and inform the relatives about the DCD procedure. The donation procedure started after informed consent had been obtained. First, the period between withdrawal of support and the occurrence of circulatory and pulmonary arrest was estimated, using a scoring list developed for this purpose13. The DCD procedure was started only if the potential donor was expected to show circulatory arrest within 1 h after cessation of mechanical support. The liver was excluded from transplantation if it was not possible to predict the time of circulatory arrest, if the time between circulatory arrest and organ perfusion exceeded 30 min or if the criteria outlined in Table1 were not fulfilled. Donor warm ischaemia time was defined as the interval between pulmonary and circulatory arrest and the start of organ perfusion.

Allocation

All three Dutch liver transplant centres agreed to allocate livers of DCD donors according to the national waiting list. In analogy with marginal DBD livers, centres were allowed to refuse a graft, for example if the recipient had a high Mayo End-Stage Liver Disease (MELD) score or if there was a large age difference between donor and recipient, in which case the liver was allocated to the next recipient on the waiting list. Factors in matching grafts with recipients that applied especially to refusal of DCD grafts were an expected long surgical procedure exceeding 8 h of cold ischaemia time, logistical reasons for an extended cold ischaemia time and combined organ transplantation. Before recipients were listed they were informed about the possibility of receiving a liver from a DCD donor. Informed consent was required. Local review boards and the Dutch Transplantation Foundation approved the protocol.

Transplantation and follow-up

Recipient operation was a standard piggy-back OLT with duct-to-duct biliary anastomosis if possible. Immunosuppression was with tacrolimus or ciclosporin, prednisolone, basiliximab with or without mycophenolate mofetil. In two of the three centres cholangiography was performed routinely between 6 and 12 weeks after OLT. Additional cholangiograms were obtained if indicated. Biochemistry, haematology, virology, monitoring of medication levels, abdominal ultrasonography and liver biopsies were performed according to protocol and as indicated.

Outcome

Primary endpoints were graft survival, patient survival and non-anastomotic biliary stricture. Graft survival was defined as the interval from first transplant from 2001 onwards until graft loss, patient death or last follow-up. Patient survival was defined as the interval between first transplant from 2001 onwards and patient death or last follow-up. Non-anastomotic biliary stricture was defined as biliary stricture more than 1 cm above the biliary anastomosis requiring endoscopic or radiological dilatation and stenting or surgery. Secondary endpoints were primary non-function, defined as non-life-sustaining function of the liver requiring retransplantation or leading to death within 7 days after OLT in the absence of vascular thrombosis; vascular and biliary complications; retransplantation; and aspartate aminotransferase levels at 1, 3 and 7 days after OLT.

Statistical analysis

Fisher's exact test, χ2 test and t test for independent samples were used. Kaplan–Meier survival analysis was performed with comparison by means of the log rank test. Cox regression analysis was carried out to identify risk factors for graft loss and non-anastomotic biliary stricture; factors with P < 0·100 were entered into a multivariable model with stepwise forward addition and backward removal of factors. Included in the analysis were variables that have previously been identified as possible risk factors in the literature. Donor risk factors for graft loss and non-anastomotic biliary stricture were age, sex, body mass index and cause of death. Operative variables were preservation solution, donor warm ischaemia time, cold ischaemia time, recipient warm ischaemia time, total warm ischaemia time (the combination of donor and recipient warm ischaemia time), total ischaemia time (total warm ischaemia plus cold ischaemia time) and transplant centre. Recipient variables were age, sex, indication for OLT, previous liver transplant and MELD score. Patients with missing values were excluded from analysis. Analysis for possible confounders, and for interaction between variables and of variables with time, including time-dependent Cox regression analysis, was carried out. P < 0·050 was considered significant. SPSS® version 16.0 for Windows® (SPSS, Chicago, Illinois, USA) was used for statistical analysis.

Results

A total of 526 OLTs were performed, 471 with DBD and 55 with DCD grafts.

DCD donors were younger than DBD donors and stroke was less often the cause of death (Table2). In accordance with protocol most DCD livers were procured with HTK solution, whereas most DBD livers were preserved in UW solution. Owing to strict selection criteria, 25 per cent of potential DCD donors were excluded from donation. By definition, DCD livers had a donor warm ischaemia time, ranging from 6 to 33 min. Cold ischaemia time, recipient warm ischaemia time, total warm ischaemia time and total ischaemia time were all (deliberately) shorter in DCD than in DBD transplantations. The ratio of DCD and DBD liver transplants did not differ significantly between the three centres.

Table 2. Characteristics of donors and recipients
 DCD (n = 55)DBD (n = 471)P
  • Values in parentheses are percentages unless indicated otherwise;

  • *

    values are mean (range).

  • DCD, donation after cardiac death; DBD, donation after brain death; MELD, Mayo End-Stage Liver Disease; UW; University of Wisconsin; HTK, histidine–tryptophan–ketoglutarate.

  • χ2 test unless indicated otherwise;

  • t test for independent samples.

Donor
 Age (years)*37 (12–64)45 (11–72)< 0·001
 Sex ratio (M : F)33 : 22224 : 2470·087
 Cause of death  < 0·001
  Trauma17 (31)99 (21·0) 
  Cerebrovascular22 (40)330 (70·1) 
  Other16 (29)42 (8·9) 
Recipient
 Age (years)*49 (18–65)47 (10–70)0·340
 Sex ratio (M : F)40 : 15275 : 1960·042
 Indication for transplantation  0·208
  Postnecrotic cirrhosis24 (44)219 (46·5) 
  Primary sclerosing cholangitis13 (24)81(17·2) 
  Primary biliary cirrhosis5 (9)27 (5·7) 
  Acute liver failure0 (0)39 (8·3) 
  Metabolic disease3 (5)36 (7·6) 
  Other10 (18)69 (14·6) 
 Previous transplant3 (5)52 (11·0)0·203
 MELD score*17·4 (6–40)17·9 (6–52)0·712
Preservation and operation
 Preservation solution  < 0·001
  UW13 (24)422 (89·6) 
  HTK42 (76)49 (10·4) 
 Donor warm ischaemia time (min)*16·5 (6–33)< 0·001
 Cold ischaemia time (min)*456·2 (290–765)515·3 (60–1090)0·008
 Recipient warm ischaemia time (min)*34·6 (18–64)39·4 (16–161)0·018
 Total warm ischaemia time (min)*51·9 (27–81)39·4 (16–161)< 0·001
 Total ischaemia time (min)*508·1 (331–846)553·8 (83–1121)0·038
 No. of transplants per centre  0·063
  A20 (36)102 (21·7) 
  B18 (33)198 (42·0) 
  C17 (31)171 (36·3) 

Outcome of transplantation

The incidence of primary non-function, biliary leakage and vascular complications did not differ between DCD and DBD OLTs (Table3). Aspartate aminotransferase levels were higher in the DCD group at 24 h and 7 days after surgery, but not at 3 days. Patient and graft survival rates did not differ between DCD and DBD transplants (Table3, Figs1 and 2). If centre B was excluded, 1-, 2- and 3-year graft survival rates also did not differ between DCD OLT (84, 75 and 75 per cent respectively) and DBD OLT (85·0, 83·0 and 80·6 per cent) (P = 0·406).

Figure 1.

Patient survival in the first 3 years after orthotopic liver transplantation (OLT) with a donation after cardiac death (DCD) or donation after brain death (DBD) graft. P = 0·763 (log rank test)

Figure 2.

Graft survival in the first 3 years after orthotopic liver transplantation (OLT) with a donation after cardiac death (DCD) or donation after brain death (DBD) graft. P = 0·212 (log rank test)

Table 3. Outcome of liver transplantation
 DCD (n = 55)DBD (n = 471)P§
  • Values in parentheses are percentages unless indicated otherwise;

  • *

    values are mean(s.d.);

  • values in parentheses are s.d.

  • Defined as non-life-sustaining function of the liver requiring retransplantation or leading to death within 7 days after orthotopic liver transplantation in the absence of hepatic artery thrombosis.

  • DCD, donation after cardiac death; DBD, donation after brain death; AST, aspartate aminotransferase.

  • §

    χ2 test unless indicated otherwise;

  • t test for independent samples;

  • #

    log rank test.

Early graft function
 Immediate function54 (98)464 (98·5) 
 Primary non-function1 (2)7 (1·5)0·844
Ischaemia–reperfusion damage 
(AST, units/l)* 
 24 h2423(3471)1311(2154)0·007
 3 days410(342)359(577)0·692
 7 days90(68)63(48)0·061
Biliary complications
 Leakage2 (4)2 (0·4)0·415
 Non-anastomotic stricture13 (24)37 (7·9)< 0·001
Vascular complications  0·502
 Hepatic artery thrombosis4 (7)22 (4·7)0·438
 Other4 (7)16 (3·4)0·542
Graft survival (%)
 1 year74 (6)80·4 (1·8)0·275#
 3 years68 (7)74·5 (2·1)0·212#
Patient survival (%)
 1 year85 (5)86·3 (1·7)0·704#
 3 years80 (6)80·8 (2·0)0·763#
Retransplantation during follow-up10 (18)49 (10·4)0·081
 Non-anastomotic stricture6 (11)12 (2·5)< 0·001
 Vascular complications3 (5)18 (3·8)0·261
 Primary non-function1 (2)7 (1·5)0·200
 Chronic liver failure0 (0)12 (2·5)0·625

The 3-year cumulative percentage of surviving grafts developing non-anastomotic biliary strictures, censored for retransplantation or patient death, was higher for DCD than for DBD OLT (31 (s.e. 8) versus 9·7 (1·5) per cent; P < 0·001) (Fig.3). The uncensored incidence of non-anastomotic biliary strictures was 13 (24 per cent) of 55 in DCD and 37 (7·9 per cent) of 471 in DBD OLT (P < 0·001). Retransplantation for non-anastomotic biliary stricture was more frequent in the DCD group (P < 0·001) (Table3).

Figure 3.

Cumulative percentage of surviving grafts with non-anastomotic biliary stricture (NAS) after orthotopic liver transplantation (OLT) with a donation after cardiac death (DCD) or donation after brain death (DBD) graft. P < 0·001 (log rank test)

Risk factors for graft loss

Univariable analysis of risk factors in DCD transplantation revealed cold ischaemia time, recipient warm ischaemia time and transplant centre as possible risk factors for 1-year graft loss. Univariable analysis of risk factors in DBD OLT revealed severe head trauma as cause of donor death, total ischaemia time and transplant centre as possible risk factors for 1-year graft loss (Appendix 1, supporting information). When entered as continuous instead of categorical variables, increasing cold ischaemia time and recipient warm ischaemia time were associated with a continuously increasing risk and were therefore entered as continuous variables in the multivariable model. Independent risk factors for graft loss within 1 year are shown in Table4. If recipients with acute liver failure were removed, independent risk factors for 1-year graft loss were similar (data not shown). No confounders or interactions among variables and of variables with time were present.

Table 4. Independent risk factors for graft loss within 1 year identified by multivariable logistic regression analysis
 Odds ratioP
  1. Values in parentheses are 95 per cent confidence intervals.

All patients
 Centre A2·28 (1·21, 4·28)0·011
 Centre B3·26 (1·88, 5·64)< 0·001
 Cold ischaemia time1·00 (1·00, 1·00)0·033
 Recipient warm ischaemia time1·02 (1·00, 1·03)0·024
Donation after brain death
 Centre A2·42 (1·25, 4·67)0·009
 Centre B3·10 (1·76, 5·47)< 0·001
 Recipient warm ischaemia time1·02 (1·00, 1·04)0·010
 Severe head trauma as cause of donor death1·68 (1·06, 2·66)0·026
Donation after cardiac death
 Centre B8·36 (1·01, 68·92)0·049
 Donor warm ischaemia time1·09 (1·00, 1·18)0·041
 Cold ischaemia time1·01 (1·00, 1·01)0·010

The retransplantation rate in centre B (31 of 216) was higher than in centre C (12 of 188) (P = 0·015), but no different from that in centre A (16 of 122) (P = 0·870). In DCD OLT the total ischaemia time was greater in centre B (mean 512 min) than in centres A and C (506 min) (P = 0·040). There was only a trend towards a longer cold ischaemia time in centre B (mean 466 min) compared with centres A and C (451 min) in DBD transplantation (P = 0·051). The recipient warm ischaemia time was shorter in centre B (34 min) than in centres A and C (43 min) in DBD OLT (P = 0·018). Donor warm ischaemia times did not differ between the three centres. Recipient age and sex of donor and recipient did not differ between centres. Donor age for DCD and DBD OLT combined was lower in centre B (mean 43·8 years) than in centres A and C (47·8 years) (P = 0·047).

Risk factors for non-anastomotic biliary stricture

For OLT with a DBD donor univariable risk factors for non-anastomotic biliary strictures were donor age and primary sclerosing cholitis (PSC) as underlying liver disease, and a trend for MELD-score. For OLT with a DCD donor no other risk factor for non-anastomotic biliary strictures was identified in univariable analysis (Appendix 2, supporting information). This remained unchanged if recipients with acute liver failure were excluded from the analysis (data not shown). Independent risk factors for non-anastomotic biliary stricture identified by multivariable analysis are shown in Table5.

Table 5. Independent risk factors for non-anastomotic biliary stricture identified by multivariable regression analysis
 Odds ratioP
  1. Values in parentheses are 95 per cent confidence intervals. DCD, donation after cardiac death; PSC, primary sclerosing cholangitis; MELD, Mayo End-Stage Liver Disease.

All patients
 DCD graft5·58 (2·75, 11·31)< 0·001
 PSC in recipient2·59 (1·40, 4·80)0·002
 Donor age1·02 (1·00, 1·05)0·041
Donation after brain death
 PSC in recipient3·64 (1·72, 7·72)0·001
 MELD score1·04 (1·00, 1·08)0·027

In the first 6 months after OLT, 11 of 31 instances of non-anastomotic biliary stricture were in recipients with PSC, compared with six of 19 that developed more than 180 days after OLT (P = 0·767). Independent risk factors for non-anastomotic biliary stricture after exclusion of recipients with PSC are shown in Table6. Non-anastomotic biliary stricture occurred more frequently in centres A (15 of 122) and C (22 of 188) than in centre B (13 of 216) (P = 0·040). The retransplantation rate for non-anastomotic biliary strictures was 12 of 13 in centre B, five of 15 in centre A and none of 22 in centre C (P < 0·001). The independent risk factors did not explain the different incidence of non-anastomotic biliary stricture and retransplantation rate between centres. No confounders or interactions among variables and of variables with time were present.

Table 6. Independent risk factors for non-anastomotic biliary stricture identified by multivariable regression analysis after exclusion of recipients with primary sclerosing cholangitis
 Odds ratioP
  1. Values in parentheses are 95 per cent confidence intervals. DCD, donation after cardiac death; MELD, Mayo End-Stage Liver Disease.

All patients
 DCD graft8·65 (3·48, 21·54)< 0·001
 MELD score1·01 (1·01, 1·08)0·011
 Donor age1·01 (1·01, 1·07)0·012
Donation after brain death
 MELD score1·06 (1·02, 1·10)0·003
 Donor age1·04 (1·00, 1·08)0·036

Centre effect

For both DCD and DBD OLT, graft and patient survival rates were lower in centre B than in centres A and C (Figs4 and 5). This difference persisted and increased with time after exclusion of patients with acute liver failure and retransplantation (Fig.6). MELD scores were similar in the three centres. In the DBD group there was a higher 30-day mortality rate in centre B (11·1 per cent, 24 of 216) than in centres A (3·3 per cent, 4 of 122) and C (2·7 per cent, 5 of 188). The operative mortality rate in centre B was 3·7 per cent (8 of 216) compared with zero (0 of 310) in centres A and C combined (P < 0·001). In DCD OLT the single intraoperative death occurred in centre B; the 30-day mortality rate was three of 18 in centre B compared with one of 37 in centres A and C combined (P = 0·099).

Figure 4.

Graft survival in the first 3 years after donation after brain death (DBD) orthotopic liver transplantation (OLT) in relation to centre. P < 0·001, centre B versus centre C; P = 0·082, centre B versus centre A; P = 0·124, centre C versus centre A (log rank test)

Figure 5.

Graft survival in the first 3 years after donation after cardiac death (DCD) orthotopic liver transplantation (OLT) in relation to centre. P = 0·042, centre B versus centre C; P = 0·184, centre B versus centre A; P = 0·364, centre C versus centre A (log rank test)

Figure 6.

Patient survival (donation after cardiac death and donation after brain death combined) in the first 3 years after orthotopic liver transplantation (OLT) in relation to centre, after exclusion of recipients with acute liver failure and retransplanted patients. P = 0·028, centre B versus centre C; P = 0·047, centre B versus centre A; P = 0·761, centre C versus centre A (log rank test)

Discussion

In this study similar rates of patient and graft survival, primary non-function and hepatic artery thrombosis were found in DCD and DBD OLT. This is very unusual in DCD transplantation and probably the result of a strict protocol with predefined donor acceptance criteria, as recently proposed by others11–14. As allocation was according to the waiting list and MELD scores were similar, selection of recipients was no different for DCD and DBD OLT in the Dutch 2001 protocol.

Initial reports demonstrated that DCD OLT was feasible, but the incidence of primary non-function, hepatic artery thrombosis and non-anastomotic biliary stricture was increased, with lower graft and patient survival5–10, 15. Those series included uncontrolled DCD donors. Subsequently, new guidelines and a donor risk index were formulated16, 17. The data from the United Network for Organ Sharing (UNOS) also revealed worse graft and patient survival, and more primary non-function after DCD than DBD OLT18 in a study that included livers from both controlled and uncontrolled DCD donors. Favourable DCD donor criteria were: donor age 45 years or less, donor warm ischaemia time 15 min or less and a maximum of 10 h cold ischaemia time. In OLT from DCD donors with these criteria, graft survival was similar to that after DBD transplantation19. More recently similar patient survival after DCD and DBD OLT was reported from Pittsburgh, whereas graft survival was lower in DCD transplantation, especially in the first year11. In 2009 Mayo Clinic Jacksonville, including only category III DCD donors, reported similar patient and graft survival in DCD and DBD OLT20. However, a matched-pairs analysis from the UK with similar predicted mortality for DCD and DBD transplantation recently showed worse graft and patient survival, and more non-anastomotic biliary strictures and hepatic artery thrombosis, in DCD than in DBD OLT21.

A centre effect on survival was evident in the present cohort. As this occurred in both DCD and DBD OLT it did not affect the comparison of survival between the two types of donor. A higher operative and immediate postoperative mortality rate in one centre explained most of this effect. The data would seem to indicate that other factors such as postoperative medical treatment and different ischaemia times in this centre may also have played a role in the centre effect. Despite a lower incidence of non-anastomotic biliary stricture in DBD OLT, this centre had a higher retransplant rate, especially for this indication. It is known that retransplantation carries a lower patient survival22. In treating non-anastomotic biliary stricture, it is therefore important first to use endoscopic or radiological dilatation procedures or to convert to a bilioenteric anastomosis, if possible.

Non-anastomotic biliary stricture occurred more frequently after DCD than DBD OLT. This was similar to results in other series with less strict donor selection23, 24. Only one group has reported similar complication rates, including non-anastomotic biliary stricture, in DCD versus DBD transplantation14. Non-anastomotic biliary stricture may be a reflection of more severe ischaemia–reperfusion damage in DCD OLT as indicated by the present finding of higher aspartate aminotransferase serum levels on days 1 and 7 than in DBD transplantation. However, ischaemia times and aminotransferase levels in the first week after OLT were not found to be risk factors for the development of non-anastomotic biliary stricture.

As reduced perfusion of the peribiliary plexus may play a role in development of non-anastomotic biliary stricture it is common practice to use a low-viscosity solution for rapid perfusion of the DCD graft, including high-pressure perfusion of the biliary arterial plexus. Some centres prefer a high-viscosity solution for preservation thereafter. A recent study showed decreased graft survival in HTK-preserved livers, especially of DCD livers with a cold ischaemia time above 8 h25. The present data do not allow analysis of which solution is best.

In this study, donor age and recipient MELD score contributed to the risk of non-anastomotic biliary stricture, and PSC in the recipient was an important risk factor in DBD grafts. A DCD graft carried such a high risk that other risk factors became insignificant. Although UNOS advocates using DCD livers in ‘low-risk’ recipients, and the Dutch relationship between MELD and biliary strictures seems to support this, Pittsburgh reported a larger survival benefit of DCD livers for recipients with a MELD score exceeding 30, similar to data reported in DBD OLT26.

One-year graft loss for DBD was determined by centre, recipient warm ischaemia time, and donor severe head trauma. DCD 1-year graft loss was influenced by centre, donor warm ischaemia time and cold ischaemia time. Prolonged, severe hypotension in the donor in the postextubation period is a better predictor of subsequent organ function than time from extubation to asystole27. More than 15 min of systolic blood pressure below 50 mmHg was an exclusion criterion in the present protocol. A longer interval correlates with increased rates of diffuse biliary ischaemia, graft loss or death27. Donor age influenced the incidence of non-anastomotic biliary stricture in this Dutch cohort but had no direct impact on graft or patient survival. A recent report also found similar graft and recipient survival rates in DCD and DBD OLT, with a similar incidence of primary non-function and hepatic artery thrombosis, but an increased risk for the development of non-anastomotic biliary stricture in the DCD group (13·7 versus 1 per cent; P = 0·001)28. Donor weight over 100 kg and total ischaemia time of at least 9 h in donors aged more than 50 years predicted the development of non-anastomotic biliary stricture in the DCD group. In the present series these risk factors were avoided by protocol (Table1)28. In the Scientific Registry of Transplant Recipients (SRTR) DCD donors were younger (P < 0·001), with fewer deaths secondary to stroke (P < 0·001), and there was a higher graft failure rate within the first 180 days compared with DBD OLT. Listing for retransplantation and graft failure progressed over 180 days versus 20 days in DBD transplantation. However, in the SRTR DCD recipients were older (P < 0·001), with lower MELD scores (P < 0·001)29. In the present series there was no significant difference in graft survival between DCD and DBD OLT, although this may be due to a type II error. The recent series from Pittsburgh analysed 114 DCD OLTs between 1993 and 2007, whereas the Dutch cohort included patients between 2001 and 200611. Although donor warm ischaemia time was limited by protocol, in Pittsburgh more biliary complications were present in DCD transplantations and half of these led to retransplantation; donor warm ischaemia time over 20 min, cold ischaemia time exceeding 8 h and donor age greater than 60 years were associated with poorer outcomes. All of these factors were avoided by protocol in the present cohort from the Netherlands; this cohort was more homogeneous.

The introduction of DCD transplantation has not led to an increase in the number of OLTs performed. Since 2001 the number of DBD donations has continued to decrease and there has been a steady increase in DCD donors30. Multiple reasons are being suggested for this, such as better hospital care for neurological disorders and decreasing numbers of fatal traffic accidents. Further reduction in ischaemia times, increased use of non-retransplantation solutions for postoperative problems, and optimization of surgical and postoperative care may further improve graft survival in both DCD and DBD OLT. This includes better preservation and selection of donors.

The present data indicate that national sharing of livers from selected controlled DCD donors may result in long-term graft and patient survival rates similar to those after DBD OLT. This requires a protocol with only controlled (category III) donors, restrictive acceptance criteria and national agreement about the procurement technique, which allows allocation according to a national waiting list. Reducing the rates of non-anastomotic biliary stricture, ischaemic damage and retransplantation is important for further improvement.

Acknowledgements

The authors thank Ron Wolterbeek (Department of Medical Statistics, Leiden University Medical Centre, Leiden, The Netherlands) for excellent help with statistical analysis. The authors declare no conflict of interest.

Supporting information may be found in the online version of this article.

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