ORIGINAL ARTICLE. Received August 28, 2008; accepted December 22, 2008.

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1 LIVER TRANSPLANTATION 15: , 2009 ORIGINAL ARTICLE Extended Right Liver Grafts Obtained by an Ex Situ Split Can Be Used Safely for Primary and Secondary Transplantation with Acceptable Biliary Morbidity Atsushi Takebe, 1,3 Harald Schrem, 1 Bastian Ringe, 1 Frank Lehner, 1 Christian Strassburg, 2 Juergen Klempnauer, 1 and Thomas Becker 1 Departments of 1 General, Visceral, and Transplantation Surgery and 2 Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany; and 3 Division of Hepato-Biliary- Pancreatic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan Split liver transplantation (SLT) is clearly beneficial for pediatric recipients. However, the increased risk of biliary complications in adult recipients of SLT in comparison with whole liver transplantation (WLT) remains controversial. The objective of this study was to investigate the incidence and clinical outcome of biliary complications in an SLT group using split extended right grafts (ERGs) after ex situ splitting in comparison with WLT in adults. The retrospectively collected data for 80 consecutive liver transplants using ERGs after ex situ splitting between 1998 and 2007 were compared with the data for 80 liver transplants using whole liver grafts in a matched-pair analysis paired by the donor age, recipient age, indications, Model for End-Stage Liver Disease score, and high-urgency status. The cold ischemic time was significantly longer in the SLT group (P 0.006). As expected, bile leakage from the transected surface occurred only in the SLT group (15%) without any mortality or graft loss. The incidence of all other early or late biliary complications (eg, anastomotic leakage and stenosis) was not different between SLT and WLT. The 1- and 5-year patient and graft survival rates showed no statistical difference between SLT and WLT [83.2% and 82.0% versus 88.5% and 79.8% (P 0.92) and 70.8% and 67.5% versus 83.6% and 70.0% (P 0.16), respectively]. In conclusion, ERGs can be used safely without any increased mortality and with acceptable morbidity, and they should also be considered for retransplantation. The significantly longer cold ischemic time in the SLT group indicates the potential for improved results and should thus be considered in the design of allocation policies. Liver Transpl 15: , AASLD. Received August 28, 2008; accepted December 22, In 1988, the first description of successful split liver transplantation (SLT) using a left lateral graft (LLG) for a pediatric recipient and the remnant extended right graft (ERG) for an adult recipient was reported by our institution. 1 Since then, with increasing experience and improvement of the surgical technique, the significant potential of SLT became apparent, and this modality soon became common practice. 2-5 SLT demonstrated great merit for very small children who were otherwise very unlikely find a suitable donor of a full size liver graft. Living-related liver donation of LLGs for pediatric recipients was introduced later into the repertoire of liver transplant techniques 6 and is now a well-established method with the disadvantage of the inherent risks for the healthy living donor. Therefore, SLT still has a place in pediatric and adult liver transplantation. Abbreviations: AST, aspartate aminotransferase; BMI, body mass index; CIT, cold ischemic time; ERG, extended right graft; GRBW, graft/body weight ratio; HAT, hepatic arterial thrombosis; HU, high urgency; ICU, intensive care unit; LDLT, living donor liver transplantation; LLG, left lateral graft; MELD, Model for End-Stage Liver Disease; NS, not significant; PNF, primary nonfunction of the graft; SLT, split liver transplantation; WLG, whole liver graft; WLT, whole liver transplantation. Address reprint requests to Thomas Becker, M.D., Ph.D., Department of General, Abdominal, and Transplantation Surgery, Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, 30625, Hannover, Germany. Telephone: ; FAX: ; becker.thomas@mh-hannover.de DOI /lt Published online in Wiley InterScience ( American Association for the Study of Liver Diseases.

2 SAFE USE OF EX SITU EXTENDED RIGHT LIVER GRAFTS 731 Today, the splitting procedure can be done either in situ during the liver procurement procedure in the braindead donor or alternatively ex situ after whole liver harvesting, but both methods are considered to increase the risk for biliary complications. 7 Biliary complications belong to the most serious morbidities of all types of liver transplantation 8 and are closely related to the graft and preoperative recipient conditions. 9 An analysis of living donor liver transplantation (LDLT) 10 has shown that partial liver grafts have a higher incidence of biliary complications because of their transected surface and the operation procedure, which includes surgical dissection in the hepatic hilum. Even though the number of published cases is comparatively limited so far, high rates of biliary morbidity have also been reported for ERGs with an incidence of 10% to 34% Despite this clear disadvantage, the use of ERGs after an in situ or ex situ split is basically acceptable for most patients because of the ubiquitous shortage of donor organs. In clinical practice, in situ splitting to avoid longer cold ischemic times (CITs), with associated damage to the graft leading potentially to significant increases in morbidity and mortality, is often restrained by logistical and technical efforts and expertise as well as financial expenditures, all of which are necessary for its success. Although most publications on SLT using in situ split ERGs have demonstrated comparable patient and graft survival in comparison with whole liver transplantation (WLT), the value and safety of ex situ splitting in obtaining ERGs for liver transplantation remain controversial, even though in practice about half of all SLT procedures in Europe and the United States are done after an ex situ split. 2,16,17 Some centers hesitate to use ERGs obtained by an ex situ split either in general or for complicated or retransplant cases. In most published series, ERGs have been mainly or exclusively used for primary liver transplantation in adult recipients This study investigates the common complications and details the biliary complications and results after the transplantation of ERGs obtained by ex situ splitting in comparison with whole liver grafts. This study also includes high-urgency cases and retransplants, all of which were performed at our institute. Our aim is to evaluate the value of the use of ex situ split ERGs in comparison with whole liver grafts under different circumstances. PATIENTS AND METHODS This study evaluated 80 consecutive split liver transplants using ERGs after ex situ splitting within the last decade ( ). In this period, among a total of 1205 liver transplants, 80 ERGs and 94 LLGs, which were all obtained by ex situ splitting, were used. These 80 recipients of ERGs were selected for this study and matched to adult recipients who received WLGs in the same period of time. The following matching criteria were used: 1. Donor age ( 50 and 50). 2. Recipient age ( 50 and 50). 3. Indication. 4. Model for End-Stage Liver Disease (MELD) score. 5. High-urgency status according to the Eurotransplant status. Definition of Complications Vascular complications were defined as problems in the hepatic artery, portal vein, or hepatic vein requiring therapeutic invasive interventions. Renal dysfunction was defined as renal failure requiring transient hemodialysis. Respiratory insufficiency was defined as prolonged intubation ( 5 days) or reintubation. Neurological complications were diagnosed by a neurologist. Postoperative bleeding was identified as bleeding requiring 3 units of blood after transplantation or needed surgical management. Ascites was defined as uncontrollable ascites with drug therapy. A wound malignancy was defined as some type of wound complication that needed secondary surgical management. Acute rejection was diagnosed by pathological findings. An infection event was defined as any kind of infection that required antibiotics or an invasive procedure. Biliary complications were defined as bile leakage from the transected liver surface or bile leakage from the anastomosis site (including leakage from the cystic duct and stump of the left bile duct) or bile duct necrosis or stenosis. Donor and Recipient Selection Well-experienced transplant surgeons made decisions based on macroscopic observation and the anatomical situation on the basis of these criteria: 1. Donor age below 50 years. 2. Hemodynamic stability. 3. Preferable donor intensive care unit (ICU) stay of less than 5 days. 4. No status of hypernatremia with Na 170 mmol/l. Every patient with any condition who agreed to receive ERGs was considered to be a potential recipient of SLT. Surgical Technique The ex situ splitting procedure has been described in a previous report. 18 In summary, (1) preoperative cholangiography and angiography were not performed on the donor, (2) a surgical metal probe was used to demonstrate all vessels, (3) the sharp-knife technique 19 was used for the parenchymal transection, and (4) the bile duct was transected to allow minimum dissection in the hepatic hilum at the final step. The implantation techniques of ERGs and WLGs were identical. Furthermore, (1) neither the piggyback technique nor a venous-venous bypass was used; (2) no portocaval shunt was made; (3) the arterial tree of the celiac trunk and the common bile duct of the graft were used with the ERG for anastomosis; (4) in most cases, the vascular anastomosis was performed in an end-to-end fashion for the portal vein and the suprahepatic and infrahepatic vena cava, whereas arterial reconstruction was performed with the branch-patch technique (gastroduodenal artery gastroduodenal artery) 20 ; (5) for biliary recon-

3 732 TAKEBE ET AL. TABLE 1. Donor and Recipient Characteristics SLT (n 80) WLT (n 80) P Donor Age (years) 33.0 (7 60) 38.1 (14 64) NS Stay in ICU (days) 3.9 (1 14) 5.45 (1 44) Graft weight (g) 1141 ( ) 1753 ( ) GRBW (%) 1.78 ( ) 2.36 ( ) CIT (minutes) 747 ( ) 662 ( ) Recipient Age (years) 41.6 (15 65) 43.4 (18 64) NS MELD 16.2 (6 40) 17.2 (6 40) NS Number of HU 8 (10.0%) 8 (10.0%) NS Follow-up (months) 40.0 ( ) 40.0 (0 109) NS Abbreviations: CIT, cold ischemic time; GRBW, graft/body weight ratio; HU, high urgency; ICU, intensive care unit; MELD, Model for End-Stage Liver Disease; NS, not significant; SLT, split liver transplantation; WLT, whole liver transplantation. struction, the first choice was the duct-to-duct method by end-to-end anastomosis depending on the indications for transplantation; and (6) biliary drainage (Ttube) was used rarely and only for high-risk cases. A Roux-en-Y biliary reconstruction was used for cholestatic disease. Statistics In a matched-pair analysis, continuous variables were compared with the Mann-Whitney U test, and categorical variables were compared with Fisher s exact test. The survival rates were calculated according to the Kaplan- Meier method. Differences in the survival curves were compared with log-rank statistics. Statistical significance was defined as P JMP version 5.0 (SAS Institute, Cary, NC) was used for all statistical analysis. RESULTS Donor and Recipient Characteristics The characteristics of the donors and recipients are compared in Table 1. The median length of the donor ICU stay was 1.5 days shorter (P 0.045) and the median CIT was 85 minutes longer (P 0.006) in the SLT group. As expected, the graft weight (P 0.001) and graft/body weight ratio (P 0.001) were significantly higher in the WLT group in comparison with SLT. There was no significant difference between WLT and SLT in terms of the chosen matching criteria described previously. The median follow-up durations of SLT and WLT were equal (40 months). The most frequent indication for transplantation was cholestatic disease (36.3%). There were 10 cases of retransplantation (12.5%) in both groups. The causes of retransplantation were distributed identically between SLT and WLT, and half of them were high-urgency cases (Table 2). Comparison of Common Complications in the SLT and WLT Groups TABLE 2. Indications for Transplantation n % Fulminant liver failure Cholestatic disease Cirrhosis Malignant tumor Metabolic disease Cystic liver or benign tumor Retransplantation PNF (HU) 2 Vascular complication (HU) 3 Recurrence of hepatitis 2 Chronic rejection 3 Total Abbreviations: HU, high urgency; PNF, primary nonfunction of the graft. The incidences of complications in the SLT and WLT groups are compared in Table 3. Not only crucial complications [vascular complications, biliary complications, and primary nonfunction of the graft (PNF)] but also milder ones occurred at statistically comparable rates. There were no statistical differences in the average length of stay in the ICU in both groups. Biliary Complications To evaluate the detailed incidence of biliary complications in the SLT group, the type of biliary reconstruction and the specific biliary complications are shown in Table 4. Forty-eight patients (60.0%) in the SLT group and 50 patients in the WLT group (62.5%) received duct-toduct biliary reconstruction. A T-tube was used in 5 patients (6.3%) in the SLT group and in 1 patient (1.2%) in the WLT group. For 2 patients in the SLT group and 1 patient in the WLT group, the biliary reconstruction was not accomplished because of hemodynamic instability during the transplantation. However, a second operation intended for biliary reconstruction was canceled in all 3 cases because of the patient s death. In total, 32 biliary complications in 26 patients in the SLT group (32.5%) and 25 biliary complications in 19 pa-

4 SAFE USE OF EX SITU EXTENDED RIGHT LIVER GRAFTS 733 TABLE 3. Common Complications of Liver Transplantation SLT [n (%)] WLT [n (%)] P Primary nonfunction 6 (7.5) 2 (2.5) NS Vascular complications 12 (15.0) 6 (7.5) NS Biliary complications 26 (32.5) 19 (23.8) NS Cardiac complications 2 (2.5) 2 (2.5) NS Renal dysfunction 10 (10.0) 16 (20.0) NS Respiratory insufficient 10 (10.0) 13 (16.3) NS Neurological complications 2 (2.5) 3 (3.8) NS Postoperative bleeding 9 (11.3) 9 (11.3) NS Ascites 8 (10.0) 7 (8.8) NS Wound malignancy 6 (7.5) 7 (8.8) NS Acute rejection 15 (18.8) 12 (15.0) NS Infection event 15 (18.8) 7 (8.8) NS Date of ICU stay 16.0 (0 124) 14.1 (1 118) NS Abbreviations: ICU, intensive care unit; NS, not significant; SLT, split liver transplantation; WLT, whole liver transplantation. TABLE 4. Biliary Reconstruction and Details of Biliary Complications SLT [n (%)] WLT [n (%)] P Biliary reconstruction Duct to duct 48 (60.0) 50 (62.5) NS Roux-en-Y 32 (40.0) 29 (36.3) NS No reconstruction 2* (2.5) 1* (1.2) NS Biliary complications Total 26 (32.5) 19 (23.8) NS Early onset ( 90 days) 21 (26.3) 11 (13.8) 0.04 Leakage (transected surface) 12 (15.0) 0 (0.0) Leakage (anastomotic) 5 (6.3) 5 (6.3) NS Bile duct necrosis 5 (6.3) 2 (2.5) NS Anastomotic stenosis 2 (2.5) 6 (7.5) NS Related graft loss 2 (2.5) 2 (2.5) NS Late onset ( 90 days) 9 (11.3) 10 (12.5) NS Anastomotic stenosis 9 (11.3) 10 (12.5) NS Related graft loss 1 (1.3) 0 (0.0) NS Abbreviations: NS, not significant; SLT, split liver transplantation; WLT, whole liver transplantation. *Because of the patient s death, biliary reconstruction was not performed. Including leakage from the anastomotic site, cystic duct, and stump of the left bile duct. tients in the WLT group (23.8%) were observed during the study period. SLT demonstrated a higher risk of early-onset ( 90 days) biliary complications (26.3% versus 13.8%, P 0.04) in comparison with WLT. However, except for bile leakage from the transected surface, which is a particular complication of SLT, the number of patients with other early-onset biliary complications was the same in both groups (n 11, 13.8%). All of the late-onset ( 90 days) biliary complications in both groups were characterized by anastomotic stenosis. The incidence of anastomotic stenosis was not significantly different between the SLT and WLT groups. Overall, there were 5 graft losses (SLT 3, WLT 2) that were related to biliary complications. The difference in the incidence of these graft losses was not statistically significant between SLT and WLT. The possible clinical factors associated with early- and late-onset biliary complications after SLT were statistically analyzed. These factors included donor factors (age, length of the donor s ICU stay, graft/body weight ratio, and CIT), patient factors (age, body mass index, preoperative MELD score, urgency of operation, and indication), and other factors such as the type of biliary reconstruction and the postoperative maximum aspartate aminotransferase value. A univariate analysis did not indicate that any of these factors were a risk factor for the observed biliary complications. Bile Leakage from the Transected Surface After SLT After SLT, 12 patients were diagnosed with bile leakage from the transected surface, which is particularly inherent to SLT in comparison with WLT. In 8 of these 12 patients, this was a solitary biliary complication. This type of complication was easily controlled by percuta-

5 734 TAKEBE ET AL. TABLE 5. Univariate Analysis of Factors Associated with Leakage from the Transected Surface Leakage( ) Leakage( ) P Total number Donor age (yrs) 28.2 (17 54) 33.9 (7 60) NS Donor ICU stay (days) 4.75 (1 14) 3.83 (1 11) NS GRBW 1.79 ( ) 1.73 ( ) NS CIT (min) ( ) ( ) NS Recipient age (yrs) 36.1 (18 58) 42.6 (15 65) NS Recipient BMI (kg/m 2 ) 23.2 (17 32) 23.1 (15 35) NS MELD score 13.9 (6 27) 16.8 (6 40) NS HU 1 (8.3%) 7 (10.3%) NS Cholestatic disease 8 (66.7%) 21 (30.9%) Retransplantation 1 (8.33%) 9 (13.2%) NS Duct to duct 5 (41.7%) 43 (63.2%) NS Maximum AST (IU/L) 2062 ( ) 2314 ( ) NS Abbreviations: AST, aspartate aminotransferase; BMI, body mass index; CIT, cold ischemic time; GRBW, graft/body weight ratio; HU, high urgency; ICU, intensive care unit; MELD, Model for End-Stage Liver Disease; NS, not significant. neous drainage in 2 of 8 cases, whereas reoperation (abdominal drainage or repair of the point of leakage) was necessary in the other 6 patients (6/8, 75.0%). There was no graft loss in these 8 cases. Four patients were diagnosed with combined biliary complications. In 2 of those patients, bile leakage from the transected surface was combined with bile leakage from the anastomotic site. One patient received endoscopic biliary drainage, whereas the other underwent new biliary reconstruction. Two patients were retransplanted because of bile duct necrosis combined with bile leakage from the transected surface. One of these 2 patients died after retransplantation. Late-onset biliary complications were not associated with bile leakage from the transected surface (P 0.83). The association between leakage from the transected surface and the aforementioned clinical factors was analyzed statistically (Table 5). The incidence of leakage from the transected surface was found to be significantly higher only in patients with cholestatic disease (66.7% versus 30.9%, P 0.019) in comparison with patients who were transplanted for other indications. All other clinical factors had no significant association with this biliary complication. Patient and Graft Survival Kaplan-Meier estimations of graft and patient survival were compared by a log-rank analysis. The 1- and 5-year survival of SLT patients was 83.2% and 82.0%, respectively. The patient survival of WLT patients at the same time points was 88.5% and 79.8%, respectively (Fig. 1A). The differences between SLT and WLT in overall graft survival did not reach statistical significance (P 0.92). The 1- and 5-year graft survival rates showed no statistical difference between SLT and WLT (70.8% and 67.5% versus 83.6% and 70.0%, P 0.16; Fig. 1B). Twenty-five grafts were lost after SLT during the last decade (19 graft losses in the WLT group). Seventeen graft losses occurred within the first month after transplantation (10 in the WLT group). With significance for graft survival, the incidence of PNF and hepatic arterial thrombosis (HAT) was slightly increased in the SLT group (PNF, 7.5% versus 2.5%, P 0.13; HAT, 13.6% versus 6.3%, P 0.17) in comparison with the WLT group, but this difference did not reach statistical significance. DISCUSSION The major aim of SLT is to provide a graft of a suitable size for a small child without decreasing the number of available donor organs for adult recipients. Although the initial results for SLT were not satisfying, later, with the establishment of modern surgical techniques and further progress in the field of liver transplantation, several reports could demonstrate that SLT has potential equal to that of WLT not only for pediatric recipients but also for adult recipients. 2,13,15 Because of the ubiquitous shortage of donor organs, ERGs have become an essential option for almost every adult recipient, especially in high-volume transplantation centers with sufficient experience with this procedure. The current study clearly supports this opinion because the results have demonstrated that ERGs can be transplanted with comparable results in comparison with WLT with respect to patient and graft survival, and the significantly increased morbidity due to biliary complications appears to be acceptable. This is remarkable because in the current series, ERGs were also used for high-urgency and retransplant cases, whereas other published series used ERGs only for primary transplantation in stable patients It is well accepted that early and late biliary complications are still some of the most severe morbidities after liver transplantation, and their incidence has been reported to be between 10% and 30% after liver transplants from brain-dead donors In addition, it has been reported that the potential risk for biliary morbidities is associated with both the type of biliary recon-

6 SAFE USE OF EX SITU EXTENDED RIGHT LIVER GRAFTS 735 Figure 1. The overall survival of the SLT and WLT groups ( ). (A) The overall patient survival of the SLT and WLT groups. The 1- and 5-year survival rates (Kaplan-Meier) were 83.2% and 82.0% in the SLT group and 88.5% and 79.8% in the WLT group (P 0.92). (B) The overall graft survival in the SLT and WLT groups. The 1- and 5-year survival rates (Kaplan-Meier) were 70.8% and 67.5% in the SLT group and 83.6% and 70.0% in the WLT group (P 0.162). Abbreviations: SLT, split liver transplantation; WLT, whole liver transplantation. struction and the type of parenchymal transection. Therefore, in partial liver transplantation, reduced-size liver transplantation, SLT, and LDLT, a higher incidence of biliary complications is to be expected Especially in terms of bile leakage from the anastomotic site and late-onset stenosis, the published reports have also noted that the incidence of biliary complications is significantly higher in full right grafts after living-related donation in comparison with WLGs. 27,28 The preservation of the blood supply to the biliary tract at the donor and recipient ends is the major concern in biliary reconstruction because of its significance for a successful biliary anastomosis. An ischemic biliary tract will lead to a critical biliary complication known as an ischemic-type biliary lesion. 29,30 The dissection along the biliary tract should not be close to the wall of the biliary duct so that the fine arterial plexus covering the surface of the biliary tract remains intact and is not damaged. In addition, the right side of the hepatic hilum is normally not dissected. As a result of these technical principles, there is no difference between SLT and WLT in terms of biliary morbidity except for transected surface leakage. In this context, it is noteworthy that in the current study, fatal biliary morbidity in the SLT and WLT groups was similar in the short term and the long term. This result strongly supports the principal approach to using ERGs. In addition, biliary complications are related to the patient s condition, blood type incompatibility, CIT, HAT, and cytomegalovirus infection Among the parameters that we investigated, no factors associated with biliary complications were identified. In particular, it should be emphasized that severe preoperative conditions of the recipient (eg, high MELD score, high urgency, and retransplantation) were not associated with increased biliary complications in the SLT group. In this study, it became clear that bile leakage from the transected surface is the only additional biliary morbidity of SLT in comparison with WLT. Even with visualization of the biliary anatomy by cholangiograms prior to transection or by methylene blue injections into the biliary tree, it is difficult to avoid this complication completely. 36,37 In comparison with the lower incidence of this complication in full right grafts of LDLT, 28,38 the current results show that ERGs have a higher potential risk for biliary leakage from the transected surface. The variant biliary anatomy for segment I or IV may be difficult to recognize without preoperative examination of the biliary tree anatomy. This may be the major reason for the difference between full right grafts of LDLT and ERGs. A compromise to ERGs for adult recipients is more acceptable than a compromise to LLGs for pediatric recipients. Thereafter, the transection planes that ignore strict segmental liver anatomy at the cost of ERGs in order to preserve the relevant vessels of LLGs may be another cause of this difference. Few reports have been published on the risk factors for bile leakage from the transected surface. The decompression of the biliary tract with a T-tube may reduce bile leakage at both the anastomotic site and transected surface. 12 In our practice, on the basis of our experience, we do not use T-drains routinely. Some articles on in situ splitting data show comparable incidences of biliary complications for SLT and WLT. 14,15,39 In addition, for adult living donors who donate an LLG for pediatric transplantation, only very small incidences of bile leakage from the transacted surface have been reported. 40 This may indicate a potential advantage for in situ splitting. For the vast majority of shipped grafts, the donor harvesting operations are performed by transplant teams that are completely independent of and unrelated to the team that performs the recipient operation in Germany. This circumstance may be a confounding factor for the high percentage of ex situ splitting versus in situ splitting. Furthermore, in comparison with in situ splitting, the ex situ procedure of splitting requires much fewer financial and human resources in order to be successful. Because the ex situ

7 736 TAKEBE ET AL. splitting procedure is done in most cases in the transplant center that intends to use the LLGs, acceptance of ERGs by other centers requires a high degree of professional trust in order to overcome skepticism about the quality of the ERGs. The current study clearly shows that this trust must be justified. In several studies, a multivariate analysis of a huge number of liver transplants has demonstrated that split or reduced liver grafts are not significant risk factors for HAT and PNF. 41,42 However, in the current study, the incidence of HAT and PNF was slightly higher in the SLT group than in the WLT group without reaching statistical significance. This observation should not be neglected with respect to the slightly less favorable graft survival curve for SLT, especially in the early postoperative phase. Prolonged CIT is one of the critical risk factors for HAT and PNF. 43,44 The present results show that the SLT group has a significantly prolonged CIT in comparison with the WLT group. In addition, the CIT is extended both by the splitting time itself and, in many cases with shipped ERGs, by the transport time to the center that accepts the ERGs for transplantation. To redress the difference in CIT between SLT and WLT is one of the biggest assignments of ex situ splitting. There are no other reports about ERGs after ex situ splitting for adult recipients with a meaningful number of cases and without recipient selection. Therefore, it is difficult to precisely compare the current data with results published by other transplant centers. In terms of the short-term survival rate, the current data can be compared with the University of California at Los Angeles group (1-year patient/graft survival, 78%/69%), 4 even though in this report only the in situ technique was applied. A comparison of the current results with a report published by the Hamburg group (5-year patient/graft survival, 78.4%/77.3%) 15 and a report published by the Bergamo group (5-year patient/graft survival, 94%/94%) 13 shows room for improvement. The probable reasons for these differences are that at least 50% of their data were based on in situ split transplantation and that more difficult cases such as secondary transplantation were eliminated in both reports. The results of a multicenter analysis for right trisegmental grafts after ex situ splitting from Texas showed a shorter CIT (average CIT, 586 minutes) in ex situ split transplantation in comparison with the current results (average CIT, 747 minutes). 11 Therefore, every effort should be made to shorten the CIT, although that study reported much less favorable long-term patient survival (40%-50% after 5 years) in comparison with the current results. The number of patients with a very severe preoperative condition (MELD 30) was insufficient to reach statistical significance (SLT 8, WLT 8). Nevertheless, the comparable mortality in the 2 groups (SLT 3/8, WLT 3/8) suggests that ERGs have sufficient potential even in very severe situations. In addition, no contraindications have been identified for the use of an ERG for high-risk patients if the clinical circumstances are well balanced. The average MELD score in both groups was around 17. This number seemed to be slightly inconsistent with the average condition of the recipients. For this reason, before the conversion of the allocation rules of ERGs to agree with normal allocation rules with the MELD system in Germany, ERGs are predominately used for recipients with cholestatic disease who have a very small chance of getting a suitable organ graft despite the risk of cholangiocarcinoma and the repeated risk of cholangitis. This study has shown that cholestatic disease is a significant risk factor for bile leakage from the transected surface. Unfortunately, there is no satisfactory explanation for this observation at the moment. It is important to note in this context that there was no significantly higher incidence of late biliary complications in patients with cholestatic disease after the transplantation of ERGs in comparison with WLTs. In conclusion, the use of ERGs contributes significantly to enabling pediatric liver transplantation, and ERGs can be used safely without increased mortality and with acceptable morbidity and should also be considered for retransplantation. The significantly longer CIT in the SLT group indicates a relevant potential for improved results that should be considered in the design of allocation policies and for the distribution of local resources in order to allow simultaneous transplantation of both grafts after liver splitting at the same center. REFERENCES 1. 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