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Ann Surg. 2006 December; 244(6): 865–873.
doi: 10.1097/01.sla.0000247254.76747.f3.
PMCID: PMC1856626
Long-term Outcome of Split Liver Transplantation Using Right Extended Grafts in Adulthood
A Matched Pair Analysis
Christian Wilms, MD, Jessica Walter, MD, Maren Kaptein, MD, Lars Mueller, MD, Christian Lenk, MD, Martina Sterneck, PhD, Christian Hillert, MD, Lutz Fischer, PhD, Xavier Rogiers, PhD, and Dieter C. Broering, PhD
From the Department of Hepatobiliary Surgery and Solid Organ Transplantation, University Hospital Hamburg Eppendorf, University of Hamburg, Hamburg, Germany.
Abstract
Objective:
Shortage of suitable organs led to the development of alternative techniques in liver transplantation. Split liver transplantation (SLT) is well established in pediatric patients. SLT is not completely accepted in adult recipients due to potential increased risk of complications. Despite satisfying results of short-term outcome, there is a leak on information of the long-term outcome. Therefore, we compared the outcome after transplantation of the right extended liver lobe with whole liver transplantation (WLT) using a matched pair's analysis.
Patients and Methods:
From the period of January 1993 to February 2005, 70 SLT recipients were matched with 70 WLT recipients of whole livers. Matching criteria were: 1) indication for transplantation, 2) United Network for Organ Sharing (UNOS) status, 3) recipient age, 4) donor age, 5) cold ischemic time, and 6) year of transplantation. The outcome was analyzed retrospectively.
Results:
Mean follow-up was 36 months. The 2- and 5-year patient survival rates after SLT and WLT were 86.3% and 82.6%, and 78.4% and 75.6%, respectively (log rank, P = 0.2127). Two- and 5-year graft survival rates were 77.3% and 77.3% after SLT and 71.9% and 65.8% after WLT, respectively (log rank, P = 0.3822). The total biliary complication rate was 11.4% in the SLT group versus 10.0% in the WLT group in the short-term course, while it was 8.5% after SLT and 10.0% after WLT in the long-term course. We did not observe significant differences between the groups in term of short- and long-term morbidity.
Conclusion:
Transplantation of the right extended lobe deriving from left lateral splitting of deceased donor livers is followed by the same long-term patient and graft survival, which is known from WLT. There were no differences in the complication rates even in long-term outcome implementing that SLT does not put the adult recipient to an increased early and late risk. Transplantation of the extended right liver lobe provides a safe and efficient procedure in adult patients to expand the number of available grafts.
 
Over the last 15 years, left lateral split liver transplantation (SLT) has evolved from an experimental procedure to a standardized treatment modality for children with end stage liver disease1–4 Apart from the benefit for the children, there persists apprehension that the implantation of the right extended lobe is associated with a disadvantage for the adult recipient.5
The early period of SLT was characterized by a discussion about the viability of segment IV of the right extended lobe and its potential risk of inducing early or late septic (abscess, necrosis, etc) and biliary complications including the development of segmental secondary biliary cirrhosis in the adult recipient.
The first reports about SLT documented a higher rate of postoperative morbidity (biliary complications, bleeding).2,6,7 After passing the learning curve at the end of the last decade, more and more reports about convincing early results after left lateral splitting encouraged the transplantation community to popularize the splitting procedure.2 To date, the published reports about left lateral SLT are characterized by a short follow-up while long-term results are still rare.
The scientific tools to analyze the outcome of transplantation of the extended right lobe compared with that after transplantation of a whole liver are limited to uncontrolled studies since prospective randomized trials are not possible. To answer the question if the left lateral SLT puts the adult patient on risk during the early postoperative period and the long-term follow-up, we performed a retrospective analysis of the results after transplantation of the right extended lobe in adults compared with those after whole liver transplantation (WLT) using matched pairs and a standardized classification of postoperative morbidity.
PATIENTS AND METHODS
In 1993, a split liver program has been started at the University of Hamburg. Since this time, splitting procedure has been considered in all suitable donors. Between January 1993 and February 2005, 1116 liver transplants (LTX) (675 adults, 441 children) were performed at our center. A total of 545 patients received full-size organs (473 adults, 72 children), 56 received reduced size grafts (3 adults, 53 children), 169 grafts from living donors (40 adults, including 3 dual graft transplantations, 129 children), and 341 split organs (158 adults, 183 children). Five were performed as domino transplantation (1 adult, 4 children). An informed consent for a split liver graft was obtained from all patients. The 341 SLTs consisted of 135 extended right-, 161 left lateral-, 25 full-left-, and 20 full-right grafts resulted. Among the 135 extended right grafts, 116 were primary (104 adults, 12 children) and 19 were retransplantations. These 104 adult recipients of primary right extended lobes (segments I, V–VIII) were subjects of this study and matched to adult recipients who primarily received a full-size organ within the same period of time.
Donor and Recipient Selection Criteria of SLT
Decision to split a graft of a deceased heart-beating donor was made by an experienced transplant surgeon according to the following criteria: 1) macroscopic aspect of the liver, 2) fatty degeneration (<30%), 3) vascular and 4) biliary anatomy, 5) donor age (<50 years), 6) laboratory findings (sodium <160 mmol/L, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) less than double of the normal value), 7) stay in intensive care unit (ICU) (<5 days), 8) cause of death, 9) amount of catecholamine, and 10) cold ischemic time <14 hours.
No exclusive selection criteria existed in recipients of an extended right lobe. Preferable criteria were: 1) first LTX, 2) United Network for Organ Sharing (UNOS) status IIb, III–IV, and 3) no previous significant upper abdominal surgery.
Surgical Technique
The procedure for obtaining in situ split liver grafts was entirely comparable with that for living donation and described elsewhere.8,9 The common trunk of the hepatic artery and portal vein remained with the right graft if the organ was primarily allocated to an adult recipient and remained with the left lateral split if a child was the first recipient. Parenchymal transection was performed ex situ by the sharp knife technique as introduced by Daniel Azoulay.
During hepatectomy, the recipient's hepatic artery and portal vein were kept as long as possible to allow vascular anastomosis without using interposition grafts. Since 1998, for implantation of the extended right graft, venous anastomosis was performed in piggy-back-technique. Portal vein anastomosis was performed in end-to-end fashion. Arterial anastomosis was performed with the aid of magnification loops (4×) mainly end-to-end between the right hepatic artery or common hepatic artery of the graft and the common hepatic artery of the recipient. Biliary reconstruction was performed using magnification loops in end-to-end fashion (WLT group, n = 61; SLT group, n = 59), occasionally as a Roux-en-Y-hepaticojejunostomy (WLT group, n = 9; SLT group, n = 11).
Matching Procedure
Matching procedure was performed according to following criteria: 1) indication for transplantation, 2) urgency of the recipient according to the UNOS status I–IV, 3) recipient age (<55, >55 years), 4) donor age (<55, >55 years), 5) cold ischemic time (<15 hours) 6) period of transplantation (first period, 1993–1995; second period, 1996–2000; third period, 2001–2005). Using these criteria a total of 70 matched pairs of adult recipients of right extended grafts (37 from ex situ and 33 from in situ split) and whole organs were identified. The matching was done blinded to patient outcomes. All splits in this study resulted in left lateral (segments II and III) grafts for pediatric recipients and extended-right grafts (segments I, IV–VIII) for adult recipients. Short-term course (<90 days) as well as long-term course (>90 days) of these 140 recipients were separately and retrospectively analyzed.
Immunosuppression
For standard immunosuppression, patients received cyclosporine (WLT group, 38; SLT group, 38) or tacrolimus (WLT group, 18; SLT group, 15) combined with corticosteroids. In the SLT group, in 17 patients immunosuppressive therapy was extended using either azathioprine (n = 11) or mycophenolate mofetil (n = 5) or sirolimus (n = 1). In the WLT group in 14 patients, a triple therapy was given (cyclosporine + azathioprine/mycophenolate mofetil + corticosteroids, n = 7/6; tacrolimus + mycophenolate mofetil + corticosteroids, n = 1). Acute rejection was treated with a three-day course of methylprednisolone bolus therapy (500 mg/day).
Definition of Negative Outcome
To evaluate mortality (“failure to cure”) and morbidity (“complications”), Clavien et al designed a classification of “negative outcome” in LTX, based on stratifying the complication with regard to its severity.10 We used this classification for the evaluation of mortality and morbidity in our series.
According to the original classification grade I complications carry minor risks. A grade I complication is “not life threatening,” does not result in “residual disability,” and has a “spontaneous resolution.” No invasive therapeutic intervention, except a simple bedside therapy and no specific drug therapy is necessary, except analgesics, anti-inflammatory drugs, or immunosuppressive therapy. Grade II complications are “potentially life-threatening” but do not produce “residual disability.” A grade II complication demands a specific drug therapy (grade IIa) or interventional therapy (IIb), for example, antibiotics, prolonged parenteral nutrition, or reoperation. Grade III complications are negative events implementing “residual functional disability,” for example, renal failure. A distinction was made between “nonprogressive” (IIIa) and progressive (IIIb) complications. Grade IV complications are events related to failure to cure: either retransplantation (IVa) or death (IVb).
Definition of Specific Complications due to the Transplantation Procedure
Primary nonfunction (PNF) was defined as retransplantation within 10 days after implantation or death resulting from a nonfunctioning graft.
Primary poor function (PPF) was identified if one of the transaminases was higher than 2000 U/L; or fresh frozen plasma had to be substituted more than 5 days postoperatively. Fresh frozen plasma was substituted if the prothrombin time or factor V levels were below 35%.
Biliary complications were defined as bile duct necrosis or stenosis or bile leakage requiring surgical or endoscopic intervention. Bile leakage was defined as total bilirubin in drainage fluid that doubled serum total bilirubin.
Rejection was defined as increasing transaminases levels accompanied by signs of rejection on biopsy. No protocol biopsies have been performed.
Statistics
Values are shown as medians and ranges. Survival rates were calculated according to the Kaplan-Meier method. Differences in survival curves were compared using log rank statistics. Fisher exact test was used for categorical variables. Mann-Whitney U test was used for continuous nonparametric variables. A P value <0.05 was considered statistically significant. SPSS version 11.5 (SPSS, Chicago, IL) was used for all statistical analyses.
RESULTS
Recipients and Donors
Out of 104 adult recipients of primary SLT, 70 recipients of right extended grafts could be matched with 70 recipients of primary WLT (Tables 1 and 2). The remaining 34 recipients of right extended lobes could not be correctly matched. Evaluation of the outcome of these nonmatched patients showed a 5-year patient and graft survival of 85.3% and 76%, comparable to that of the studied SLT group.
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TABLE 1. Recipient Characteristics
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TABLE 2. Indication for Transplantation
The median follow-up time was 36 months (range, 1–156 months). Eight patients (11%) were lost to follow-up.
The donor characteristics and laboratory findings did not differ significantly between SLT and WLT group (Table 3).
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TABLE 3. Donor Characteristics
Overall Incidence of Mortality and Morbidity
Seventeen patients in the WLT group (24.1%) and 12 patients in the SLT group (17.1%) died. Six of the WLT recipients underwent retransplantation (8.6%); 1 patient had a third transplantation (1.4%). In the SLT group, 9 patients were retransplanted (12.9%) and 1 patient had a third transplantation (1.4%). In both groups, every patient had at least one complication of any kind (morbidity rate, 100%). The total number of observed complications was in the WLT group n = 232 versus n = 236 in the SLT group.
Short-term Course
During the postoperative course, the transaminase peak level was significant higher in the SLT group at day 3 and day 7. ALT was 370 IU/L (range, 22–2024 IU/L) in the SLT group and 228 IU/L (range, 21–2002 IU/L) in the WLT group on day 3 (P = 0.027). On day 7, ALT was 139 IU/L (range, 8–1430 IU/L) in the SLT group versus 96 IU/L (range, 13–1345 IU/L) in the WLT group (P = 0.035). Neither prothrombin time or total bilirubin and γ-glutamyl transferase (γ-GT) differed significantly between the groups (Fig. 1A–C). PPF occurred in 4 patients of the WLT group (6%) and in none of the SLT group (P = 0.06). The rate of PNF was comparable in both groups. The incidence of reoperation was 25% in the WLT group versus 20% in the SLT group (P = 0.55). Main reasons for reoperation were postoperative bleeding (WLT group, 11% vs. SLT group, 10%), biliary complications and infections of any kind. The rate of biliary complications was 11.4% in the SLT group (reoperation: bile leakage from the cut surface n = 3, bile duct stenosis n = 1; endoscopic/antibiotic intervention: infected bilioma n = 1, cholangitis n = 3) and 10% in the WLT group (reoperation: bile duct necrosis: n = 2, bile duct stenosis: n = 1; endoscopic/antibiotic intervention: duct stenosis or choledocholithiasis n = 3, cholangitis n = 1). None of the recipients of the SLT group suffered from a segment I or IV necrosis leading to reoperation or percutaneous drainage.
figure 6FF1
FIGURE 1. Alanine aminotransaminase (A), γ-glutamyltransferase (B) and total bilirubin course (C) after WLT and SLT.
No further vascular complications regarding the portal vein or venous outflow were observed in both groups.
The 3-month patient survival rate in the WLT group was 88.6% versus 84.3% in the SLT group (P = 0.67, log-rank test) (Fig. 4). None of the deaths in the SLT group was related to the splitting procedure itself (Table 4). The 3-month graft survival rate in the WLT group was 84.3% versus 75.7% in the SLT group (Fig. 3). Graft failure caused by arterial thrombosis was observed in 2 patients of the SLT group and in none of the patients following WLT (P = 0.5) (Table 5). In the WLT group, 5 recipients were UNOS status I patients with 3-month patient and graft survival rates of 60%. In the SLT group, 6 UNOS status I patients showed patient and graft survival rates of 50% and 17%, respectively.
figure 6FF4
FIGURE 4. Patient survival according to Kaplan-Meier (log rank, P = 0.67).
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TABLE 4. Cause of Death Within the Short-term and Long-term Course
figure 6FF3
FIGURE 3. Graft survival according to Kaplan-Meier (log rank, P = 0.43).
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TABLE 5. Reasons for Graft Loss Within the Short-term and Long-term Course
Regarding the overall morbidity using the Clavien classification, the incidence of grades I–IV complications did not differ significantly between both groups (Fig. 2). Grades I and IIA complications were predominant. The most frequent grade I complication was biopsy proven rejection, while the most common grade IIA complications were infections (Table 6).
figure 6FF2
FIGURE 2. Specific complications within short-term and long-term course presented according to the morbidity classification of Clavien et al.10
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TABLE 6. Specific Complications Within Short-term and Long-term Course in SLT and WLT
Long-term Course
The number of patients death was 12 in the WLT group versus 6 in the SLT group (Table 6). Graft loss occurred in 3 patients of the WLT group and in 2 patients of the SLT group (Table 5). Neither in SLT group nor in WLT group later patient and graft loss was related to vascular or biliary complications. The actual 5-year patient and graft survival rates in the WLT group and SLT group were 75.7% and 67.1%, and 82.8% and 74.3%, respectively (P = 0.43 and 0.67, log-rank test) (Figs. 3, 4).
The rate of biliary complications was 8.5% in the SLT group (reoperation: bile duct stenosis n = 2; endoscopic/antibiotic treatment: bile duct stenosis n = 2, choledocholithiasis n = 1, recurrent cholangitis n = 1) and 10% in the WLT group (P = 0.59; reoperation: mechanical obstruction of the bile duct caused by a neurinoma located at the hepatoduodenal ligament n = 1, necrotic bile duct lesion n = 1; endoscopic/antibiotic treatment: choledocholithiasis n = 2, recurrent cholangitis n = 2 chronic cholangitis concomitant with chronic cholestases due to multiple biliary strictures n = 1).
Regarding overall morbidity, among the predominating grade I complications, arterial hypertension and metabolic disorders were most frequent while acute rejections were infrequent. In both groups, rates of grade II complications decreased while grade III complications leading to lasting disability increased (Fig. 2). The most common grade III complication was renal failure. In 5 patients of the SLT group, hemodialysis was required (P = 0.06). Another important cause of grade III complications was diabetes mellitus and obesity (Table 6). Grade IV complications were in both groups first of all related to recurrence of the underlying disease.
With regard to the patient, graft survival, and incidence of specific complications, both WLT and SLT groups did not differ significantly within the long-term course.
DISCUSSION
The severe shortage of suitable donor organs with consequential high mortality on the waiting list for LTX led to the development of techniques to increase the organ pool, including SLT and living donor liver transplantation (LDLT). The SLT procedure was introduced in the late 1980s of the last century and has been refined over the past 15 years. Therefore, SLT led to significant improvement in survival on the pediatric waiting list11 with excellent results nearly equal to those of WLT in children.12–17 In opposite, the initial results in transplantation of extended right liver grafts in adult recipients showed to be worse compared with those of WLT.18 Despite improving technique and results, SLT itself is still considered to be a risk factor for poor outcome in LTX.5 Data on long-term outcome of SLT are rare. In the time from January 1988 to June 2003, only 4% of the LTXs performed in Europe were split or reduced-size LTX.19 The 12-month mortality was reported to be 22% in the SLT versus 18% in the WLT group.
In this single-center study, no difference between the outcome of recipients of right extended grafts compared with full-size organs in term of graft and patient survival and complications in short-term nor in long-term course were observed, emphasizing a coequal role of those grafts in LTX. To our knowledge, we are the first to report about the long-term outcome of SLT in the setting of a matched-pair analysis and more than 30 patients. By matching the SLT with the WLT recipients, we overcame the criticized systematic bias of a separately selection of SLT recipients. As well, we observed no differences in donor characteristics (Table 1) between both groups demonstrating comparable graft quality. Decision not to split the grafts in the WLT group was primarily made due to missing pediatric recipient of the left lateral lobe, anatomic variations excluding SLT procedure or other donor factors.
To evaluate the morbidity in SLT and WLT, we have chosen the Clavien classification of negative outcome in liver transplantation. The advantage of the proposed classification is to differentiate between mild, severe, up to life-threatening complications in a standardized manner. The standardization allows comparing the data between several centers and provides interpretable and reproducible information.20 In the plenty of possible common complications, the main drawback might be the evanescent focus on technique related events and problems, eg, size matching, graft function, biliary and vascular complications.
The graft size is the most important factor to avoid postoperative liver failure. By the growing experiences with SLT and LDLT, the minimum graft volume to prevent a small for size situation was considered to be 40% to 50% of the standard liver volume.21 Containing about 80% of the standard liver volume, the extended right liver graft fulfills the criteria of adult recipients. In accordance, we did not find any significant differences in the early outcome with regard to either postoperative liver function nor PPF or PNF. The only mentionable observation was a higher transaminase peak within the first 7 postoperative days in the SLT group. This might be due to the physical injury by the splitting procedure itself and the hypoperfusion of segment I and especially IV of the graft. Nevertheless, neither the size reduction nor the probable inadequate perfusion of segment IV affected the liver function at all. Even in the long-term outcome, we did not observe any specific complications with regard to potential fibrotic or cirrhotic changes of segment IV.
Regarding vascular reconstruction, neither problems in venous outflow nor a higher incidence of other vascular complications occurred in the SLT group. Thrombosis of the arteria hepatica occurred in 2 SLT recipients and in none of the WLT recipients. This difference was not significant, consistent with a recently published multivariate analysis of 1257 LTXs regarding hepatic artery thrombosis, in which split or reduced liver grafts were not observed to be a risk factor for hepatic artery thrombosis.22
Bile leakage is an expected common complication early after SLT, while bile duct stenosis is more feared in the long-term course. The published data on biliary complications range from 11.5% to 22%.13,23–26 Our short-term biliary morbidity rate in this series was 11.4% in the SLT group versus 10.0% in the WLT group in concordance with our previously published series of 40 SLT recipients matched with 40 WLT recipients with biliary complication rates within 3 months of 12.5% in the SLT versus 10% in the WLT group.26 The long-term biliary morbidity was first reported in this study with 8.5% in the SLT group versus 10% in the WLT group. The reason of the low biliary complication rates in the SLT group in the long-term course is the undisturbed biliary system of the right extended graft after left lateral splitting.
Concerning the overall morbidity, our data are accordant to the results of the large European cohort (rate of infections, 27%)19 with predominant mild complications (Clavien: grade I and grade IIA) in the short-term course. Causes of death in the early postoperative phase were not specific for the transplant procedure but mainly due to infections. Interestingly, 2 patients in the WLT group died because of acute graft failure while none in the SLT group did.
The events in the long-term course were mainly distributed to the mild and not life threatening complication groups (Clavien: grade I and grade IIA; Table 6). The most frequent observed complications even in the group of grade IIIA complications, including persistent disorders, could be seen as side effects of the current immunosuppression. The only significant difference between the groups was a higher rate of acute rejections in the long-term course after WLT (WLT group n = 6, SLT group n = 0; P = 0.048). This result might not be of great impact while the rate of acute rejections is still very low (8.5%) and those episodes did not lead to graft or patient lost.
The causes of death in the long-term course did not differ in both groups and were mainly due to the recurrence of the underlying disease and not related to the surgical procedure. Our results show that SLT has become a safe and effective procedure with no significant differences in complication rates, patient and graft survival even in the long-term course compared with the outcome after WLT. These favorable results could be achieved by improvements in surgical technique and due to the allocation of the leftover liver by the splitting surgeon to a suitable second recipient in the same center, thus minimizing cold ischemic time. Splitting of a deceased donor liver should always be considered if no contraindications are obvious.
In this study, the data are limited on the results of transplantation of extended right liver lobes, excluding those of full left and full right liver splitting. The full left and full right splitting means an additional innovative procedure to expanse the donor organ pool, but a more careful selection of donor organs and recipients is required. The procedure is a technical challenge for the surgeon, and more experience is needed to establish this technique.27
CONCLUSION
SLT has become an accepted procedure to overcome the severe organ shortage despite limited information on the long-term outcome of these patients. In this study, we did not observe any significant differences in the rate of patient and graft loss neither in the short-term nor in the long-term course. Potential split related problems, such as impaired graft function, vascular or biliary complications, were not significantly more frequent in the SLT group. This positive long-term outcome of SLT recipients indicates that left lateral SLT is an excellent and safe procedure to expand the donor organ pool with no disadvantage for the recipient's future who received the right extended lobe of a whole liver.
 
Discussions
Dr. Henri Bismuth: You have to be congratulated, Xavier Rogiers, for your continuous efforts to promote alternatives to whole liver transplant in the present organ shortage era. Today, in order to encourage the transplant community to use the split for children, you show that after removal of the left lobe or segments 2 and 3, liver grafts may be used without any harmful effect in adult patients, compared to the whole liver. This is clear, I think, and everybody will appreciate that you have reinforced your original report, that you published some years ago. Split liver replace favorably the living donor, which is important in children and today you add that the other recipients will not suffer by receiving the remaining part of the liver. However, you state that only adults are dying during waiting time, your splitting technique into 2 segments and 6 segments respectively, does not address the need to increase the pool of grafts for adults. The only way to achieve that is to split for 2 adults and your work does not deal with this point. However, looking at your figures that you published in your paper, which I had the privilege to see, you said that your experience is of 341 split livers and if you remove the 104 extended right and of course 104 left lobes at that time, you have 165 split grafts remaining. What are they and what do they become?
I am quite sure that you have the data in your series, which I think could be the largest one of split livers in the world, to answer this question. This question is more important than the one you answered today. Split for 2 adults will provide the maximum use of split livers. I remind you of the figures established by Jean Bernard Otte that 30% of the liver graft may be split. Child transplantation represents 10% of the total number of liver transplantations. Why are the other 20% not also used for splitting for 2 adults? (May I have one slide?) If we go to the European Liver Registry and this is the total number of our splits, you may see that almost since 2000 it (the number) is not increasing and if you look at the figure for children under ten years, which is the green, this is this number. For adults, I may say, adult associated children I put the same number. That means that the yellow part represents the adults plus children more than ten years. This part is very small, and if you look at the total number, it is almost 10% of the total liver transplantations performed in Europe. That means indeed that it is not increasing.
So this is why I say that in the title of your paper you say in the adult field, but you don’t say that only the part of the adult who will receive this large liver and it is only linked to the children. So this is my question. But your paper is excellent, going in the same direction as the first one, to convince us that children must be transplanted by split instead of living donor.
Dr. Christian Wilms: Thank you very much for your comments and for the additional information. The main aim of this study was to analyse if the adult recipient of the right extended liver graft is faced with a higher risk of morbidity and mortality in the short and long term. The persistent low numbers of splits in Europe underline, that a lot of transplantation centres are still reluctant in accepting split liver grafts. Additionally we have to observe that in the last years the number of living related liver transplantations for paediatric recipients are increasing despite the comparability of the results after receiving either a graft from a living donor or from splitting of a deceased donor liver.
The 341 split liver transplantations performed in our centre consisted of 135 extended right-, 161 left lateral-, 25 full-left- and 20 full-right grafts. Among the 135 extended right grafts, 116 were primary (104 adults, 12 children) and 19 were re-transplantations. The 104 adult recipients of primary right extended grafts were subject of this study. The results of full-right full-left splitting were published in the last December issue of Annals of Surgery.
Since 20–30% of the potential donors are suitable for splitting, we could supply every paediatric recipient with grafts from split liver transplantation, thus avoiding living donation for paediatric recipients. The remaining splitable deceased donor livers should be used for full-right full-left splitting. The technical development of splitting for two adults is nearly accomplished (Ann Surg, Dec. 2005). The main obstacles of this procedure are the competition with left lateral splitting and in most countries inappropriate allocation rules. To solve the first obstacle the transplantation community has to answer if it is ethical acceptable to use splitable livers for two adults thus increasing the need for the safe left lateral living donation for paediatric recipients while the need for the bigger right lobe donation from living donors could be reduced. The second obstacle can only be solved by changes in the allocation policy of split livers in a way that both hemilivers have to be allocated by the splitting surgeon himself according to the individual anatomy of the donor liver and the individual anatomy and status of the recipients behind.
Dr. Peter Neuhaus: I enjoyed your presentation very much; however, I have some questions. You did not mention fatty changes in the liver in both groups. Maybe you could comment on this. Interestingly, you had 2 patients with graft loss because of hepatitis recurrence. I would like to know whether this is hepatitis C and whether it had something to do with regeneration or other influences related to small for size problems in adult patients. I do not really understand why 7 of 70 patients needed retransplantation in this group with excellent liver grafts. I think this 10% number is somewhat high, and maybe you can comment on this.
Overall this is an excellent series.
Dr. Christian Wilms: Thank you very much for this questions. Since we did not perform routine liver biopsies in both groups, we could not analyze the detailed difference of fatty change. The second question, regarding the regeneration and recurrence of hepatitis C, we observed that the right extended lobe is normally not a small for size graft, thus limiting the need for regeneration after transplantation. This is also confirmed by our postoperative volume measurements. The recurrences of hepatitis were all related to hepatitis C. The retransplantation rate of 10% including early and late retransplantations in the long-term follow up is within the accepted range after whole organ liver transplantation.
Dr. Maarten Slooff: I think the Hamburg group has again to be complimented because they have given the closest possible proof of the efficacy of both methods. However, you state in the abstract that surgical experience is important and that is true, but I think, and I would like your comments, that two other factors are very important as well. That is that you have to select your donor and your recipients carefully. The donor/recipient combination must be fit for this type of operation. Furthermore, you need double teams; you have to have at least two experienced surgical teams for this procedure, and the resources of your hospital must be adequate. You need two operating rooms for simultaneous transplants in order to do this type of procedure and to have this type of results. Thank you.
Dr. Christian Wilms: Selection of appropriate donors and recipients is imperative to achieve these results. However, the selection of the right recipient in left lateral splitting is not as important as in full right full left splitting for two adult recipients. The right extended lobe from an adult decreased donor can serve as a graft for nearly every recipient on the waiting list. Care has to be taken in choosing high urgency recipients. Availability of two full transplant teams is recommended but not a prerequisite since in our centre a significant number of split liver transplantations including both implantations are done by one surgical team. Logistical reasons should not be used to refuse a split.
Footnotes
Christian Wilms, MD, and Jessica Walter, MD, contributed equally to the study.
Reprints: Dieter C. Broering, MD, PhD, University Hospital of Schleswig-Holstein, Campus Kiel, Arnold Heller Strasse 7, 24105 Kiel, Germany. E-mail: dbroering/at/chirurgie-sh.de.
REFERENCES
1.
Kim JS, Groteluschen R, Mueller T, et al. Pediatric transplantation: the Hamburg experience. Transplantation. 2005;79:1206–1209. [PubMed].
2.
Deshpande RR, Bowles MJ, Vilca-Melendez H, et al. Results of split liver transplantation in children. Ann Surg. 2002;236:248–253. [PubMed].
3.
Broering DC, Kim JS, Mueller T, et al. One hundred thirty-two consecutive pediatric liver transplants without hospital mortality: lessons learned and outlook for the future. Ann Surg. 2004;240:1002–1012; discussion 1012.
4.
Otte JB. History of pediatric liver transplantation. Where are we coming from? Where do we stand? Pediatr Transplant. 2002;6:378–387. [PubMed].
5.
Strasberg SM, Lowell JA, Howard TK. Reducing the shortage of donor livers: what would It take to reliably split livers for transplantation into two adult recipients? Liver Transpl Surg. 1999;5:437–450. [PubMed].
6.
Broelsch CE, Emond JC, Whitington PF, et al. Application of reduced-size liver transplants as split grafts, auxiliary orthotopic grafts, and living related segmental transplants. Ann Surg. 1990;212:368–375; discussion 375–377.
7.
Denys A, Chevallier P, Doenz F, et al. Interventional radiology in the management of complications after liver transplantation. Eur Radiol. 2004;14:431–439. [PubMed].
8.
Broering DC, Sterneck M, Rogiers X. Living donor liver transplantation. J Hepatol. 2003;38(suppl 1):119–135. [PubMed].
9.
Rogiers X, Bismuth H, Busuttil RW, et al. Split Liver Transplantation. Darmstadt, Germany: Steinkoff Verlag, 2002.
10.
Clavien PA, Camargo CA Jr, Croxford R, et al. Definition and classification of negative outcomes in solid organ transplantation: application in liver transplantation [see comment]. Ann Surg. 1994;220:109–120. [PubMed].
11.
Reyes J, Gerber D, Mazariegos GV, et al. Split-liver transplantation: a comparison of ex vivo and in situ techniques. J Pediatr Surg. 2000;35:283–289; discussion 289–290.
12.
Azoulay D, Astarcioglu I, Bismuth H, et al. Split-liver transplantation: the Paul Brousse policy. Ann Surg. 1996;224:737–746; discussion 746–748.
13.
Rela M, Heaton ND. Split-liver transplantation. Br J Surg. 1998;85:881–883. [PubMed].
14.
Kalayoglu M, D'Alessandro AM, Knechtle SJ, et al. Preliminary experience with split liver transplantation. J Am Coll Surg. 1996;182:381–387. [PubMed].
15.
Rogiers X, Malago M, Gawad K, et al. In situ splitting of cadaveric livers: the ultimate expansion of a limited donor pool. Ann Surg. 1996;224:331–339; discussion 339–341.
16.
Rogiers X, Malago M, Gawad KA, et al. One year of experience with extended application and modified techniques of split liver transplantation. Transplantation. 1996;61:1059–1061. [PubMed].
17.
Busuttil RW, Goss JA. Split liver transplantation. Ann Surg. 1999;229:313–321. [PubMed].
18.
Emond JC, Whitington PF, Thistlethwaite JR, et al. Transplantation of two patients with one liver: analysis of a preliminary experience with ‘split-liver’ grafting. Ann Surg. 1990;212:14–22. [PubMed].
19.
Burroughs AK, Sabin CA, Rolles K, et al. 3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome. Lancet. 2006;367:225–232. [PubMed].
20.
Clavien P, Camargo CA Jr, Croxford R, et al. Definition and classification of negative outcomes in solid organ transplantation: application in liver transplantation. Ann Surg. 1994;220:109–120. [PubMed].
21.
Lee SG, Park KM. An adult to adult living donor liver transplant using dual left lobe grafts. Surgery. 2001;129:647–653. [PubMed].
22.
Silva MA, Jambulingam PS, Gunson BK, et al. Hepatic artery thrombosis following orthotopic liver transplantation: A 10- year experience from a single centre in the United Kingdom. Liver Transpl. 2006;12:146–151. [PubMed].
23.
Azoulay D, Castaing D, Adam R, et al. Split-liver transplantation for two adult recipients: feasibility and long-term outcomes. Ann Surg. 2001;233:565–574. [PubMed].
24.
Gawad KA, Topp S, Gundiach M, et al. Sharing of split livers between centers is easily feasible. Transplant Proc. 2000;32:59. [PubMed].
25.
Soejima Y, Sugimachi K. Domino and split liver transplantation: technical problems. Nippon Geka Gakkai Zasshi. 2002;103:423–427. [PubMed].
26.
Broering DC, Topp S, Schaefer U, et al. Split liver transplantation and risk to the adult recipient: analysis using matched pairs. J Am Coll Surg. 2002;195:648–657. [PubMed].
27.
Broering DC, Bok P, Mueller L, et al. Splitting of the middle hepatic vein in full-right full-left splitting of the liver. Liver Transpl. 2005;11:350–352. [PubMed].