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Donor age as a risk factor in donation after circulatory death

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  • 1. Original article Donor age as a risk factor in donation after circulatory death liver transplantation in a controlled withdrawal protocol programme O. Detry1 , A. Deroover1 , N. Meurisse1 , M. F. Hans1 , J. Delwaide2 , S. Lauwick3 , A. Kaba3 , J. Joris3 , M. Meurisse1 and P. Honor´e1 Departments of 1 Abdominal Surgery and Transplantation, 2 Hepato-Gastroenterology and 3 Anaesthesiology and Intensive Care, Centre Hospitalier Universitaire de Li`ege, University of Li`ege, Li`ege, Belgium Correspondence to: Professor O. Detry, Department of Abdominal Surgery and Transplantation, CHU Li`ege, Sart Tilman B35, B4000 Li`ege, Belgium (e-mail: olivier.detry@transplantation.be) Background: Results of donation after circulatory death (DCD) liver transplantation are impaired by graft loss, resulting mainly from non-anastomotic biliary stricture. Donor age is a risk factor in deceased donor liver transplantation, and particularly in DCD liver transplantation. At the authors’ institute, age is not an absolute exclusion criterion for discarding DCD liver grafts, DCD donors receive comfort therapy before withdrawal, and cold ischaemia is minimized. Methods: All consecutive DCD liver transplantations performed from 2003 to 2012 were studied retrospectively. Three age groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant 72 h, and results at 1 and 3 years. Results: A total of 70 DCD liver transplants were performed, including 32 liver grafts from donors aged 55 years or less, 20 aged 56–69 years, and 18 aged 70 years or more. The overall graft survival rate at 1 month, 1 and 3 years was 99, 91 and 72 per cent respectively, with no graft lost secondary to non-anastomotic stricture. No difference other than age was noted between the three groups for donor or recipient characteristics, or procurement conditions. No primary non-function occurred, but one patient needed retransplantation for artery thrombosis. Biliary complications were similar in the three groups. Graft and patient survival rates were no different at 1 and 3 years between the three groups (P = 0·605). Conclusion: Results for DCD liver transplantation from younger and older donors were similar. Donor age above 50 years should not be a contraindication to DCD liver transplantation if other donor risk factors (such as warm and cold ischaemia time) are minimized. Presented to the European Society for Organ Transplantation (ESOT) 2013 Congress, Vienna, Austria, September 2013 Paper accepted 5 February 2014 Published online in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9488 Introduction Donation after circulatory death (DCD) has been proposed as a means to increase the pool of hepatic grafts1 . However, compared with donation after brain death (DBD), DCD imposes additional warm ischaemic injury before organ preservation by cooling and flushing. The results of multicentre series of DCD liver transplantation2–5 demonstrate a greater risk of graft failure as a result of non-anastomotic stricture of the graft bile ducts. Advanced donor age has been determined as a significant prognostic factor in DBD liver transplantation6. Aged livers have less regenerative capacity7 and are more susceptible to ischaemia–reperfusion injury8 and hepatitis C virus (HCV) reinfection after liver transplantation9,10. Despite these facts, there is no absolute limit of donor age for DBD liver transplantation11,12 . In DCD liver transplantation, donor age above 50 years has been identified as an additional risk factor for graft loss in multicentre series such as that of the United Network for  2014 BJS Society Ltd BJS Published by John Wiley & Sons Ltd
  • 2. O. Detry, A. Deroover, N. Meurisse, M. F. Hans, J. Delwaide, S. Lauwick et al. Organ Sharing13 , despite reports of good results in single- centre experiences14,15 . It was therefore advised13,16 that 40 or 50 years should be the age limit for DCD liver donation. In 2003, the authors initiated a controlled DCD liver transplantation programme in addition to an active DCD kidney procurement and transplantation experience17–19 . In this programme, potential DCD liver donors were selected using the same criteria as for regular DBD liver donors. In particular, no precise age criterion was applied. Cold ischaemia time was intentionally kept as short as possible, as, in Belgium, DCD liver grafts are allocated on a centre-oriented basis20 . The preliminary results of this programme have been published elsewhere21. The aim of the present study was to report on the results of the first 10 years of this experience, and particularly on graft survival and the rate of post-transplant biliary complications, according to DCD donor age. Methods This study is a retrospective evaluation of the results of the programme of controlled DCD liver transplantation developed at the University of Li`ege hospital transplan- tation centre. This programme was approved by the local ethics committee; the protocol has been described more extensively elsewhere22 . All consecutive DCD liver transplants performed between January 2003 and August 2012 were studied retrospectively. Basic immunosuppression in recipients consisted of regular triple therapy using tacrolimus, mycophenolate mofetil and steroids, from which patients were weaned progressively after 4 weeks. Follow-up was completed until 31 August 2013, allowing a minimum follow-up of 1 year for every patient. Evaluation of donor age To evaluate the influence of donor age on outcomes, the series of DCD liver transplants was divided into three groups according to donor age: 55 years or less, 56–69 years, and 70 years or more. Donation after circulatory death donors DCD donors were selected for liver donation using the same criteria as for regular DBD donors. Importantly, advanced donor age per se was not considered as an absolute contraindication to liver donation. Macroscopic evaluation of the liver at the time of procurement and graft biopsies on demand were used as final criteria to proceed with the transplantation. Preimplantation liver graft biopsies were also performed regularly. The DCD procedures were scheduled during normal working hours, and medical support withdrawals were performed in the operating room by senior anaesthesi- ologists and/or intensive care unit (ICU) physicians in DCD donors, who received intravenous heparin before withdrawal. According to protocol, DCD donors may have received comfort therapy until withdrawal of respiratory and medical support22 . At the University of Li`ege hospital, the end-of-life analgosedation of DCD donors initiated in the ICU by intensivists is regularly switched to volatile anaesthetics such as sevoflurane. This comfort therapy could inhibit respiratory reflexes23 . Circulatory arrest was diagnosed as pulseless arterial pressure of less than 40 mmHg measured on a femoral artery catheter. After a ‘no-touch’ period of 5 min (2 min early in the experience), circulatory death was declared by three physicians unrelated to the surgical procurement or transplant team. Organ harvesting was then performed using the super-rapid laparotomy and sternotomy technique, with caval decompression in the pericardium and direct aortic cannulation, as described24. Once the cold flush with pressurized University of Wisconsin (UW) solution or unpressurized histidine–tryptophan–ketoglutarate (HTK) solution had been initiated, the aorta was cross-clamped in the chest just above the diaphragm, and the abdominal and thoracic cavities were filled with iced fluid for topical cooling. After completion of the aortic flush (4–5 litres UW and 10–15 litres HTK solution), the organs were rapidly removed. Liver grafts were flushed further, ex situ, through the portal vein with 1 litre of the flush solution and then cold-stored in a standard manner until transplantation. Liver graft allocation and transplantation Liver grafts were allocated according to the Eurotransplant organization rules for Belgium. The DCD liver grafts were considered as marginal and/or experimental grafts, and were allocated in a centre-oriented manner. The recipients were selected from the waiting list according to their low surgical risk (absence of previous abdominal surgery, no retransplantation, relatively stable liver function) and their low chance of receiving a liver graft in a timely manner following the regular Model for End-stage Liver Disease (MELD) patient-oriented allocation rule. In practice, patients with hepatocellular cancer (HCC) within or beyond the Milan criteria, or patients with cirrhotic liver disease with severe complications (mainly encephalopathy and refractory ascites) but a low MELD score, were chosen when a DCD liver graft was available in the initial part of the experience. In the later part of  2014 BJS Society Ltd www.bjs.co.uk BJS Published by John Wiley & Sons Ltd
  • 3. Donation after circulatory death liver transplantation the experience, retransplantation or patients with higher MELD scores were considered. Liver grafts from DCD donors aged over 60 years were allocated preferentially to HCV-negative patients. Transplant candidates were called into the hospital before the DCD procedure, and were prepared for anaesthesia at the time of the DCD procedure in order to shorten the graft cold ischaemia time. Donor and recipient data collection In all DCD donors the following information was collected from the prospective Eurotransplant donor database: age, sex, cause of brain damage, terminal blood sodium level, terminal liver function test results, need for vasopressors, length of the ICU stay, body mass index, last 24-h diuresis and past cardiopulmonary resuscitation. The donor risk index (DRI) was calculated using the web-based Cincinnati Children’s Hospital Medical Center DRI calculator (http://gastro.cchmc.org/calculators/donor-risk-index)25 . For recipients, the following information was collected from the computerized medical file: age, sex, indication for transplant, and the laboratory MELD score at admission for transplantation. The use of heparin in the donor before cardiac arrest, the type of preservation solution (UW or HTK) and the different transplant times were collected from the Eurotransplant transplantation database. Results of graft biopsies were retrieved from medical files. Definitions In DCD donors, the total donation total warm ischaemia time was defined as the time between the withdrawal of medical support and the time of aortic perfusion with cold preservation solution. During this time interval warm ischaemia was not complete as, in general, this period is marked by progressive hypoxia and varying passages of hypotension before the cessation of all cardiopulmonary functions. Donation total warm ischaemia time was divided into two separate phases: the time of life support withdrawal to cardiac arrest (withdrawal time), and the time between cardiac arrest and aortic cannulation (acirculatory time). Cold ischaemia time was defined as the time from aortic cold perfusion until removal of the graft from iced preservation fluid. Suture time was defined as the time from the end of cold ischaemia to graft blood reperfusion by the opening of the vascular clamps. Total ischaemia time was defined as the time between withdrawal of support to graft reperfusion. Study endpoints Groups were compared for graft and patient survival, and the occurrence and management of biliary complications, as primary endpoints. Graft survival was defined as the time from liver transplantation to graft loss and/or patient death. Patient survival was considered from the first transplantation to patient death. Biliary complications sus- pected clinically and/or biologically were confirmed by magnetic resonance imaging (MRI) and/or endoscopic ret- rograde cholangiography. Patients had routine graft MRI as deemed necessary in regular follow-up. Symptomatic biliary complications were classified as non-anastomotic strictures, anastomotic strictures or biliary leaks. Secondary endpoints were peak levels of aminotrans- ferases and total bilirubin during the first 72 h after liver transplantation, and the occurrence of primary non- function and hepatic artery thrombosis. Statistical analysis Data were analysed using GraphPad Prism 6·0c software for Macintosh OSX (GraphPad Software, San Diego, California, USA). Median values with i.q.r. and/or ranges are presented, with differences evaluated by one-way ANOVA using the Kruskal–Wallis test as a post hoc comparison. Proportions were analysed with the χ2 test. Survival rates were calculated using the Kaplan–Meier method and compared with the log rank (Mantel–Cox) test. P < 0·050 was considered statistically significant. Results Between 2003 and 2012, in a consecutive series of 306 adult liver transplants, the authors performed 218 DBD, 70 DCD and 18 living related liver transplantations. In total, this DCD liver transplantation series includes 69 patients, as one patient had DCD liver retransplantation after a hepatic artery thrombosis on a first DCD liver graft. The overall median age of the recipients was 59 (i.q.r. 51·5–64, range 29–73) years; ten (14 per cent) of the recipients were women. The primary indication for liver transplantation was decompensated cirrhosis in 39 patients (alcohol-related, 21; viral, 14; other, 4), HCC in a cirrhotic liver in 25 (within the Milan criteria in 14 patients and beyond in 11 on preoperative imaging), other cancer in four (HCC in non-cirrhotic liver, 2; hepatic metastases of neuroendocrine tumour, 1; cholangiocar- cinoma complicating primary sclerosing cholangitis, 1) and retransplantation for hepatic artery thrombosis in two patients (Table 1). The median laboratory MELD score at transplantation was 15 (i.q.r. 11–20, range 6–40). All procedures were piggy-back liver transplantations with temporary portocaval shunt and laterolateral caval anastomosis, as described by Belghiti and colleagues26 .  2014 BJS Society Ltd www.bjs.co.uk BJS Published by John Wiley & Sons Ltd
  • 4. O. Detry, A. Deroover, N. Meurisse, M. F. Hans, J. Delwaide, S. Lauwick et al. Table 1 Characteristics of the graft recipients Donor group ≤ 55 years (n = 32)† 56–69 years (n = 20) ≥ 70 years (n = 18) P§ Age (years)* 58 (51–63) 60 (51–64) 59 (52–64) 0·929 Sex ratio (M : F) 29 : 3 16 : 4 15 : 3 0·536¶ Laboratory MELD score* 14·5 (11·2–17·7) 12·5 (9·2–17·7) 17·0 (14·0–25·2)‡ 0·032 Liver disease HCC in cirrhotic liver 11 11 3 Other cancer 2 1 1 Cirrhosis without cancer 17 8 14 Retransplant for HAT 2 0 0 *Values are median (i.q.r.). †One patient is counted twice as he was retransplanted for hepatic artery thrombosis (HAT); both were donation after circulatory death grafts from donors aged less than 56 years. MELD, Model for End-stage Liver Disease; HCC, hepatocellular carcinoma. ‡P = 0·036 versus 56–69 years donor age group (one-way ANOVA). §One-way ANOVA, except ¶χ2 test. Table 2 Baseline characteristics of donors Donor group Age ≤ 55 years (n = 32) Age 56–69 years (n = 20) Age ≥ 70 years (n = 18) P† Age (years)* 44 (36–51) 63 (59–67) 73 (70–77) < 0·001 Sex ratio (M : F) 22 : 10 17 : 3 12 : 6 0·347‡ Donor risk index* 1·8 (1·5–2·1) 2·3 (2·1–2·4) 2·6 (2·5–2·7) < 0·001 CPR 18 12 8 0·601‡ Cause of death – Anoxia 17 12 8 Trauma 7 1 3 Stroke 7 7 7 Other (euthanasia) 1 0 0 BMI (kg/m2)* 25 (23–29) 25 (24–29) 26 (23–28) 0·740 Intensive care stay (days)* 5 (4–8) 6·5 (5–8·7) 6·5 (3·7–9·2) 0·541 Urine output (ml/day)* 2100 (1550–3200) 2100 (1550–3250) 1775 (1234–2060) 0·096 Use of pressor agents 12 3 5 0·216‡ Sodium (mmol/l)* 145 (139–149) 143 (139–147) 141 (136–148) 0·422 Total bilirubin (mg/dl)* 0·38 (0·30–0·66) 0·30 (0·30–0·67) 0·44 (0·30-0·82) 0·275 AST (units/l)* 39·5 (24·7–59·7) 38·0 (23·5–69·0) 36·0 (26·0–69·0) 0·993 GGT (units/l)* 40 (27–118) 67 (39–118) 39 (24–92) 0·362 *Values are median (i.q.r.). CPR, cardiopulmonary resuscitation; BMI, body mass index; AST, aspartate aminotransferase; GGT, γ-glutamyltransferase. †One-way ANOVA, except ‡χ2 test. A venovenous bypass was never used. Arterial first, or simultaneous arterial and portal reperfusions, were used according to the surgeon’s preference, with no use of any fibrolytic agent. A biliary T tube was never used. Two patients had a combined DCD liver and kidney transplantation. DCD donors had a median age of 59 (i.q.r. 44–70, range 16–83) years. Anoxia was the cause of irreversible brain damage leading to withdrawal of medical support in 53 per cent of the DCD donors (37 of 70) (Table 2). Twenty-nine graft biopsies were performed, demon- strating normal liver tissue or less than 10 per cent steatosis in 26 grafts. Two biopsies showed moderate microvesic- ular steatosis, and in one graft there was severe steatosis. In the 41 remaining donor livers, the liver graft was con- sidered macroscopically to be normal and no biopsy was performed. The median total donation warm ischaemia time was 19·5 (i.q.r. 16–24, range 10–39) min, with a median with- drawal phase of 11 (7–15·5, 1–30) min and a median acircu- latory phase of 9 (8–10, 4–15) min. Median cold ischaemia time was 235·5 (200–285, 105–576) min. Median total ischaemia time was 292 (268–340, 164–661) min. Survival Median follow-up of the 70 DCD liver transplant procedures was 43 (i.q.r. 23·5–62, range 12–127) months. Overall patient survival rates at 1 month, 1 and 3 years for the 69 patients were 99, 93 and 73 per cent respectively (Fig. 1). Twenty-one patients died in the follow-up period. Causes of early (at less than 3 months) postoperative death were cardiac in one patient, and multiple organ failure and sepsis in three. Causes of later death were cancer in 12  2014 BJS Society Ltd www.bjs.co.uk BJS Published by John Wiley & Sons Ltd
  • 5. Donation after circulatory death liver transplantation 10 No. at risk Patients Grafts Patient survival Graft survival 20 30 40 50 60 Survival(%) 70 80 90 100 0 69 70 64 64 43 43 27 27 12 Time after transplant (months) 24 36 Fig. 1 Overall survival for recipients and grafts in the donation after circulatory death cohort patients (recurrence of pretransplant cancer, 7; unrelated cancer, 5) and miscellaneous in five. Overall graft survival rates were 99, 91 and 72 per cent at 1 month, 1 and 3 years respectively (Fig. 1). The cause of graft loss was recipient death in all but one case, where the patient developed graft hepatic artery thrombosis with progressive graft bile duct necrosis and underwent DCD liver retransplantation 3 months after a first DCD liver transplant. Complications Biliary complications and secondary endpoints are com- pared in Table 3. Peak levels of aminotransferases and bilirubin, and rate of primary non-function and hepatic artery thrombosis were similar for the three groups. Excluding the patient with arterial thrombosis after DCD, 14 patients had biliary complications during follow- up. Three patients developed early (at less than 3 months) anastomotic fistula, including one patient with haemobilia due to an infected fistula between the arterial and biliary anastomoses. All were managed successfully by surgical revision and hepaticojejunostomy. The arterial fistula was corrected with a saphenous vein graft. Ten patients were diagnosed with an anastomotic stricture that required endoscopic (6 patients) or surgical (2) management. In two patients, the strictures were diagnosed by MRI Table 3 Biliary complications and secondary endpoints Donor group ≤ 55 years (n = 32) 56–69 years (n = 20) ≥ 70 years (n = 18) P† Biliary complications 5 4 5 0·587‡ Fistula 0 1 2 Anastomotic stricture 5 2 3 NAS 0 1 0 Graft loss due to NAS 0 0 0 Peak AST (units/l)* 1163 (715–2693) 1416 (587–2825) 1068 (699–3078) 0·990 Peak total bilirubin (mg/dl)* 2·7 (1·9–5·3) 3·1 (1·2–6·3) 4·5 (2·6–6·5) 0·289 Primary non-function 0 0 0 Hepatic artery thrombosis 1 0 0 *Values are median (i.q.r.). NAS, non-anastomotic stricture; AST, aspartate aminotransferase. †One-way ANOVA, except ‡χ2 test.  2014 BJS Society Ltd www.bjs.co.uk BJS Published by John Wiley & Sons Ltd
  • 6. O. Detry, A. Deroover, N. Meurisse, M. F. Hans, J. Delwaide, S. Lauwick et al. Fig. 2 Endoscopic retrograde cholangiogram demonstrating non-anastomotic stricture and obstruction of the graft extrahepatic bile duct, which would normally be visible between the two arrows. This patient was treated with a plastic endoprosthesis for 6 months, and had normal liver values for more than 6 months at follow-up without a prosthesis but were not treated as the liver function test results were normal. One patient developed a non-anastomotic stricture with extrahepatic bile duct involvement that required endoscopic stenting (Fig. 2). Eighteen patients underwent cholangio-MRI that excluded anastomotic or non-anastomotic bile duct stricture at a median follow- up of 18 (i.q.r. 6–25·5, range 1–120) months after transplantation. No patient was diagnosed with diffuse symptomatic non-anastomotic stricture. Comparison according to donor age group Comparison of the DCD donor age groups is presented in Table 2 and Fig. 3. Only donor age and DRI differed between the groups. Graft recipients are compared in Table 1. Laboratory MELD score at transplantation was significantly higher in patients receiving DCD liver grafts from donors aged 70 years or above compared with that in recipients of grafts from donors aged 56–69 years. Details for the procurements and transplantations are shown in Table 4. No differences between the three groups were detected. All but one DCD procurement was performed by an experienced transplant surgeon from Li`ege, either in the university hospital (50 donors) or in a referring hospital less than 1 h away by car (19). One DCD liver graft was received from another Belgian transplant unit. Discussion This study shows good results for DCD liver trans- plantation, even with grafts from older donors, when both donation warm ischaemia and, importantly, cold ischaemia times are kept to a minimum. Short duration of ischaemia can limit the occurrence of graft loss due to non-anastomotic bile duct stricture. Furthermore, donor advanced age does not appear to compromise these results, as no difference was demonstrated between DCD liver grafts from young donors and those from septuagenarians. Compared with DBD, DCD donation imposes an added period of donation warm ischaemia that has been shown to be deleterious to the liver graft, with a higher number of graft losses linked to non-anastomotic bile duct stricture and inferior graft survival13,20 . However, some expert centres have reported excellent results14,27,28 . The present experience is unique as the DCD donations were highly controlled. In contrast to the circumstances of other groups, the ethics committee at the University Hospital of Li`ege allowed the use of so-called comfort therapy during the DCD process; there is no ethical argument forbidding the use of some analgosedation during the DCD withdrawal of life support, as this use is the rule during the withdrawal of support in terminal non-donor ICU patients22,29. By using this analgosedation, DCD donors with severe brain damage have few (if any) respiratory reflexes. Circulatory arrest by anoxia may occur rapidly in this setting, with a median withdrawal phase of 11 min. In practice, with such a limited withdrawal phase there is no point in defining the so-called ‘true warm ischaemia time’3,30, a concept that is of much more importance in DCD programmes where comfort therapy is forbidden and the DCD withdrawal phase may be long. In addition, as these controlled DCD donations are performed in the operating room, with the procurement surgical team ready, the acirculatory phase of DCD may also be limited to the 5 min of no-touch period and the rapid aortic cannulation following sternolaparotomy. This policy enabled a median total donation warm ischaemia time of 19·5 min, which compares favourably with other reported experiences3,31 . One of the notable aspects of this study is the shortest cold ischaemia reported so far for DCD liver transplantation3 . In the authors’ view, this short duration of cold ischaemia may be one of the key explanations for the absence of graft loss due to non-anastomotic stricture. The reduction of cold ischaemia time was  2014 BJS Society Ltd www.bjs.co.uk BJS Published by John Wiley & Sons Ltd
  • 7. Donation after circulatory death liver transplantation 10 No. at risk ≤ 55 years 56–69 years ≤ 55 years 56–69 years ≥ 70 years 20 30 40 50 60 Graftsurvival(%) 70 80 90 100 0 32 20 31 18 22 13 12 9 ≥ 70 years 18 17 10 8 12 Time after transplant (months) 24 36 Fig. 3 Kaplan–Meier curves comparing survival of grafts from the three donor age groups: 55 years or less, 56–69 years, and 70 years or more. P = 0·605 (log rank test) Table 4 Characteristics for procurement and transplantation of donation after circulatory death grafts Donor group ≤ 55 years 56–69 years ≥ 70 years (n = 32) (n = 20) (n = 18) P† HTK solution 30 15 17 0·078‡ Use of heparin 30 20 17 0·530‡ Donation warm ischaemia time (min)* 20 (15–22) 21 (17–28) 19 (16–27) 0·382 Withdrawal phase 10 (7–12) 13 (8–19) 9 (6–17) 0·300 Acirculatory phase 9 (8–10) 8 (7–11) 9 (7–10) 0·603 Hepatectomy time (min)* 23·0 (20·7–27·5) 24·5 (17·2–30·7) 22·5 (18·2–23·5) 0·206 Cold ischaemia time (min)* 236 (212–287) 245 (204–323) 210 (187–270) 0·395 Suture time (min)* 41 (36–47) 42 (38–46) 39 (33–44) 0·339 Total ischaemia time (min)* 299 (274–348) 306 (280–382) 277 (246–332) 0·277 *Values are median (i.q.r.). HTK, histidine–tryptophan–ketoglutarate. †One-way ANOVA, except ‡χ2 test. possible owing to the centre-oriented allocation, which permitted preparation of the potential recipient before the DCD donation itself. In addition, the combined work of two experienced surgical teams, the first performing the procurement and back-table preparation of the liver graft, and the second starting the recipient operation as soon as possible, helped greatly in this respect. In this experience, DCD donor selection was not particularly strict, as shown by the use of older DCD donors. DCD donors were selected as for DBD liver transplantation, with particular avoidance of graft steatosis. In fact, when centre-oriented graft allocation is allowed, the local team knows that, for every graft they may use locally, a local patient will benefit from liver transplantation and will be removed from the local waiting list. This is a major incentive for the use of marginal grafts that might regularly be lost in a patient-oriented allocation. The age of deceased liver graft donors has increased over the past 20 years. It has already been shown that older DBD liver grafts can provide excellent post-transplant results if there are no other risk factors and if they are not used in HCV recipients. As in other reports14,15 , the present authors’ experience shows that it is also possible to use older donors for DCD liver transplantation. In the future this population could provide a large proportion of potential DCD donations enabling the procurement of liver grafts.  2014 BJS Society Ltd www.bjs.co.uk BJS Published by John Wiley & Sons Ltd
  • 8. O. Detry, A. Deroover, N. Meurisse, M. F. Hans, J. Delwaide, S. Lauwick et al. One of the drawbacks of this study is the absence of comparison with DBD liver transplantation, which could be used as a control. However, the authors believe this com- parison would not add any interesting information. First, the groups would not be comparable, as DBD liver grafts are allocated using a MELD-based patient-oriented system by the Eurotransplant organization. In this group, most liver grafts are thus shipped from other Belgian centres, or from other Eurotransplant countries, resulting in a longer cold ischaemia time for DBD compared with DCD liver transplantation. In addition, recipient MELD scores would certainly be different. As no DCD patient lost the graft as a result of non-anastomotic stricture, and all anastomotic strictures were managed successfully, there is no reason to use a control group to demonstrate that, in the authors’ experience, DCD liver transplantation is at least equal to DBD liver transplantation, even when using older grafts. Another criticism of this paper could be that there was no systematic MRI study of DCD recipient bile ducts. The ret- rospective nature of this study did not permit this investiga- tion to be performed. In the present experience, cholangio- MRI was carried out when considered useful clinically, for instance when patients developed liver test perturbations or regular ultrasound imaging showed abnormalities. Among the 70 DCD liver transplants described in this series, one graft was lost owing to arterial thrombosis and 14 grafts developed symptomatic biliary complications. Of the 55 remaining grafts, 18 (33 per cent) were checked using cholangio-MRI at some point during follow-up, with no demonstration of significant biliary problems. It has to be noted that, in some cases, analysis of cholangio-MRI is difficult, as small bile ducts may rarely dilate in liver transplantation grafts, particularly in the DCD setting. It is possible, and even probable, that some asymptomatic DCD liver transplant recipients in this series developed some degree of asymptomatic and undiagnosed non-anastomotic stricture that might one day become a clinical problem. However, this fact is also true for DBD recipients, and a prospective study evaluating intrahepatic bile ducts using MRI would undoubtedly necessitate a blind evaluation of both DBD and DCD liver transplantation series for objective comparison of the results for the two groups. The authors consider that, with use of the present protocol, DCD liver transplantation might be the ideal option for patients with HCC within or beyond the Milan criteria, and that older DCD grafts might be suitable for patients with postalcoholic cirrhosis. Young DCD liver grafts could be used for HCV recipients. In countries where deceased DBD and DCD donation is possible, it may be ethically possible to increase the deceased graft donor pool by using DBD donors older than 55 years. Acknowledgements This study was funded in part by an unrestricted research grant from Astellas Belgium. Disclosure: The authors declare no conflict of interest. References 1 Muiesan P, Girlanda R, Jassem W, Melendez HV, O’Grady J, Bowles M et al. Single-center experience with liver transplantation from controlled non-heartbeating donors: a viable source of grafts. Ann Surg 2005; 242: 732–738. 2 Monbaliu D, Pirenne J, Talbot D. Liver transplantation using donation after cardiac death donors. J Hepatol 2012; 56: 474–485. 3 Le Dinh H, de Roover A, Kaba A, Lauwick S, Joris J, Delwaide J et al. Donation after cardio-circulatory death liver transplantation. World J Gastroenterol 2012; 18: 4491–4506. 4 Dubbeld J, Hoekstra H, Farid W, Ringers J, Porte RJ, Metselaar HJ et al. Similar liver transplantation survival with selected cardiac death donors and brain death donors. Br J Surg 2010; 97: 744–753. 5 Mallik M, Callaghan CJ, Hope M, Gibbs P, Davies S, Gimson AE et al. Comparison of liver transplantation outcomes from adult split liver and circulatory death donors. Br J Surg 2012; 99: 839–847. 6 Adam R, Karam V, Delvart V, O’Grady J, Mirza D, Klempnauer J et al. Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR). J Hepatol 2012; 57: 675–688. 7 Timchenko NA. Aging and liver regeneration. Trends Endocrinol Metab 2009; 20: 171–176. 8 Martins PN, Markmann JF. 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