Reduced Liver Transplantation Research Articles

Split Liver Transplantation

Seventy-five thousand Americans develop organ failure each year. Fifteen percent of those on the list for transplantation die while waiting. Several possible mechanisms to expand the organ pool are being pursued including the use of extended criteria donors, living donation, and split deceased donor transplants. Cadaveric organ splitting results from improved understanding of the surgical anatomy of the liver derived from Couinaud. Early efforts focused on reduced-liver transplantation (RLT) reported by both Bismuth and Broelsch in the mid-1980s. These techniques were soon modified to create both a left lateral segment graft appropriate for a pediatric recipient and a right trisegment for an appropriately sized adult. Techniques of split liver transplantation (SLT) were also modified to create living donor liver transplantation. Pichlmayr and Bismuth reported successful split liver transplantation in 1989 and Emond reported a larger series of nine split procedures in 1990. Broelsch and Busuttil described a technical modification in which the split was performed in situ at the donor institution with surgical division completed in the heart beating cadaveric donor. In situ splitting reduces cold ischemia, simplifies identification of biliary and vascular structures, and reduces reperfusion hemorrhage. However, in situ splits require specialized skills, prolonged operating room time, and increased logistical coordination at the donor institution. At UCLA over 120 in situ splits have been performed and this technique is the default when an optimal donor is available. Split liver transplantation now accounts for 10% of adult transplantations at UCLA and 40% of pediatric transplantations.

CHOLESTASIS AFTER REDUCED LIVER TRANSPLANTATION. COMPARASION TO CADAVERIC LIVER TRANSPLANTATION.

A156 Split and living donor liver transplantation in adults have emerged as good alternatives to the increasing donor shortage. In reduced liver transplantation, early cholestasis is a frequent clinical problem with confusing etiology and prognosis. Aim: The aim of this study was to compare the incidence of cholestasis in a series of reduced liver graft recipients with one of cadaveric whole liver transplant recipients. Material and Methods: From March 2000 to December 2003, 40 reduced liver transplants (RLT) with a mean graft to body weight ratio (GBWR) of 1.11±0.24 were performed in our Hospital. RLT was retrospectively compared with 80 cadaveric liver transplants (CLT) performed immediately before and after each RLT. Total bilirrubin (Bb), alkaline phosphatase (AP) and gammaGT(GGT) were mesured daily during the first week and three times a week until hospital discharge. Liver biopsy was performed when graft dysfunction occured. Cholestasis was defined as the presence of at least two of the following criteria, in the absence of acute liver rejection or hepatitis C virus recurrence: Bb > 3 mg/dl, or AP > 600 UI, or GGT > 300 UI. Results: No differences were found in either group regarding recipients’ age, sex, diagnosis and Child-Pough score, both groups were comparable except for cold ischemia time (91±45 min in CLT vs 353±131 min in RLT, p<0.05)) and donor age (33±8 years in RLT vs 45±10 years in CLT, p<0.05). During the follow-up, a significant higher biliary complication rate was found in the RLT group in comparison with CLT group (53.8% vs 12.9%, p<0.05). Incidence of cholestasis was higher in the RLT group when compared to the CLT group (48.5% vs 25.4%, p<0.05) Mean AP and GGT were significantly higher in the RLT group. (705±476 vs 483±304, p<0.05 and 470±376 vs 268±230, p<0.05). No difference in cholestasis was found when recipients of the RLT group were divided into two groups according to the presence or absence of biliary complications (46.7% vs 64.7%, p=ns). Furthermore, no correlation was found in the RLT group between cholestasis and GBWR, blood portal flow, cold ischemia time or Child-Pugh classification. Conclusion: Cholestasis is more frequent in recipients underwent reduced liver transplantation and this doesn’t seem to correlate with occurrence of biliary complications, more frequently found in these procedures.

Optimization of the use of the cadaveric liver

THE AVAILABILITY of organs for transplantation is one of the most critical limiting factors in the expansion of liver transplantation (LT) activities worldwide. In our region of Eurotransplant (ET), well-established organ procurement organization (OPO) legislation would have a major impact on organ donation. In countries with favorable legislation, including presumed consent (Austria, Belgium), the rate of liver donation is 14.7 per million population (pmp), almost double that of Holland and Germany, which have rates of 8.6 and 6.5 pmp, respectively. In Asia the situation even less encouraging, because the structure of the health-care systems and the sociocultural, economic, and legislative conditions represent a major obstacle to cadaveric organ donation and to the development of transplantation. Optimizing the use of cadaveric donors means continuing to strive to increase the supply of cadaveric livers, and to apply strict rules for the efficient use and proper administration of this very precious resource. Political and social attitudes must maintain an open mind in regard to organ donation. In the hands of health-care professionals the most logical way to increase the supply of organs is with educational programs or by rational institutional approaches, as demonstrated by the model implemented in Spain. The demand for LT (ie, the large number of patients on waiting lists) continues to heavily outweigh the “offer,” or amount, of organs available for transplantation. If the first measures fail, an alternative solution could be to regulate and limit the number of LTs; however, this would further complicate the already complex and problematic waiting-list selection process. Exclusion of more patients from selection or even more strict indication criteria, allowing only the “good candidates” to be transplanted, would be an undesirable result. High risk patients, like High Urgencies, retransplantation, or critical patient categories like very old or young, hepatitis, some tumor patients would have no chance of access to life-saving therapy. The attitude of our group has always been the opposite— that is, accepting the high-risk candidates that routinely present in large centers, and instead seeking new solutions to increase the donor organ pool. This has resulted in the development and employment of segmental liver transplantation. In 1984, the pioneering work of Broelsch, Pichlmayr, and Bismuth led to the development of reduced liver transplantation (RLT) in an attempt to reduce pediatric pretransplant mortality. Since then, RLT has became routine in pediatric L T. RLT, nevertheless, is not an efficient LT modality, because part of the liver is wasted because it has to be discarded. As a result, in our program, RLT has a number restriction parameters: very small-sized recipients; unilaterally traumatized donor livers; lower quality livers; livers not amenable to splitting; and emergency situations. More efficient organ use techniques have been in existence since living-related (LRT) and split-liver transplantation (SLT) came into being. LRT is nowadays more accepted from an ethical standpoint. After its introduction into clinical practice by Broelsch et al it found fertile terrain in Asia, due to the scarcity of cadaveric donors. It is still the most frequently used technique in the majority of Asian LT programs. We continue to use LRT, and we propose it as a standard option to parents of pediatric LT recipients. LRT is also very important in the economics of a LT program with a preponderance of cadaveric LTs. The good results and the possibility of transplanting patients in an elective condition expedites the dynamics of the waiting list. This in turn provides a chance for other patients to be transplanted earlier, in better conditions, thus helping to avoid posttransplant morbidity and retransplants. Ultimately, LRT increases the chance of survival of all patients, particularly those awaiting a cadaveric organ. The use of LRT in adults is presently under investigation as a way to decrease waiting-list mortality in larger patients. Most of the experience and innovation in this regard have come from Asian LT programs. LRT was the initial response of our program to the relatively difficult conditions imposed by the allocation rules of our OPO to a developing program. Since 1993, we were further forced to employ SLT, a technique that allows transplantation of two patients with a single cadaveric organ liver, due to the high incidence of patients dying while on

Optimization of the use of the cadaveric liver

THE AVAILABILITY of organs for transplantation is one of the most critical limiting factors in the expansion of liver transplantation (LT) activities worldwide. In our region of Eurotransplant (ET), well-established organ procurement organization (OPO) legislation would have a major impact on organ donation. In countries with favorable legislation, including presumed consent (Austria, Belgium), the rate of liver donation is 14.7 per million population (pmp), almost double that of Holland and Germany, which have rates of 8.6 and 6.5 pmp, respectively. In Asia the situation even less encouraging, because the structure of the health-care systems and the sociocultural, economic, and legislative conditions represent a major obstacle to cadaveric organ donation and to the development of transplantation. Optimizing the use of cadaveric donors means continuing to strive to increase the supply of cadaveric livers, and to apply strict rules for the efficient use and proper administration of this very precious resource. Political and social attitudes must maintain an open mind in regard to organ donation. In the hands of health-care professionals the most logical way to increase the supply of organs is with educational programs or by rational institutional approaches, as demonstrated by the model implemented in Spain. The demand for LT (ie, the large number of patients on waiting lists) continues to heavily outweigh the “offer,” or amount, of organs available for transplantation. If the first measures fail, an alternative solution could be to regulate and limit the number of LTs; however, this would further complicate the already complex and problematic waiting-list selection process. Exclusion of more patients from selection or even more strict indication criteria, allowing only the “good candidates” to be transplanted, would be an undesirable result. High risk patients, like High Urgencies, retransplantation, or critical patient categories like very old or young, hepatitis, some tumor patients would have no chance of access to life-saving therapy. The attitude of our group has always been the opposite— that is, accepting the high-risk candidates that routinely present in large centers, and instead seeking new solutions to increase the donor organ pool. This has resulted in the development and employment of segmental liver transplantation. In 1984, the pioneering work of Broelsch, Pichlmayr, and Bismuth led to the development of reduced liver transplantation (RLT) in an attempt to reduce pediatric pretransplant mortality. Since then, RLT has became routine in pediatric L T. RLT, nevertheless, is not an efficient LT modality, because part of the liver is wasted because it has to be discarded. As a result, in our program, RLT has a number restriction parameters: very small-sized recipients; unilaterally traumatized donor livers; lower quality livers; livers not amenable to splitting; and emergency situations. More efficient organ use techniques have been in existence since living-related (LRT) and split-liver transplantation (SLT) came into being. LRT is nowadays more accepted from an ethical standpoint. After its introduction into clinical practice by Broelsch et al it found fertile terrain in Asia, due to the scarcity of cadaveric donors. It is still the most frequently used technique in the majority of Asian LT programs. We continue to use LRT, and we propose it as a standard option to parents of pediatric LT recipients. LRT is also very important in the economics of a LT program with a preponderance of cadaveric LTs. The good results and the possibility of transplanting patients in an elective condition expedites the dynamics of the waiting list. This in turn provides a chance for other patients to be transplanted earlier, in better conditions, thus helping to avoid posttransplant morbidity and retransplants. Ultimately, LRT increases the chance of survival of all patients, particularly those awaiting a cadaveric organ. The use of LRT in adults is presently under investigation as a way to decrease waiting-list mortality in larger patients. Most of the experience and innovation in this regard have come from Asian LT programs. LRT was the initial response of our program to the relatively difficult conditions imposed by the allocation rules of our OPO to a developing program. Since 1993, we were further forced to employ SLT, a technique that allows transplantation of two patients with a single cadaveric organ liver, due to the high incidence of patients dying while on

Innovative techniques in pediatric liver transplantation: reduced-, split- and living-donor related liver transplantation.

In spite of the increased number of organ donations, the amount of livers available for pediatric patients does not meet requirements. In an attempt to expand the pool of grafts, several techniques of size reduction (RST) have been developed: reduced-liver transplantation (RLT), liver segment transplantation (LST), "split" liver transplantation (SLT) and living-donor liver transplantation (LDLT). The aim of this work is to study the contribution of these techniques to reduction of mortality in the waiting list and the increased risks that we inflict to our patients by using these procedures. We report our experience on RST in the last nine years (23 RLT, 5 LST, 2 SLT and 3 LDLT). More than a half of them were performed in an emergency. Overall survival in children with RST (67%) is similar to that of patients receiving a "whole graft" (74%). We did not find significant differences in the incidence of graft-related complications, only reintervention for abdominal bleeding was needed more often in the RST group (30%) than in whole graft group (24%). Our data confirm the safety of the RST procedures in the pediatric liver transplantation programs and they decrease the waiting-list mortality (2.5%) among the pediatric patients.

Liver transplantation with reduced-size donor organs.

Orthotopic liver transplantation (OLT) of the pediatric patient is often limited by the availability of a size-matched donor organ. Use of reduced liver transplantation (RLT) can increase the proportion of candidates transplanted and may reduce overall mortality. We report herein the initial clinical application of RLT in the United States. Indications for RLT included fulminant hepatic failure (n = 2), acute hepatic artery thrombosis (n = 3), and chronic liver disease unresponsive to inpatient support and more than 30 days on transplant list (n = 4). Donor hepatectomy was performed using standard techniques. Formal hepatic resection was performed ex-vivo to create a size-matched graft, from the larger donor organ, which was implanted in the orthotopic position. Between 11/84 and 4/87, 70 pediatric patients were evaluated for OLT, and 33 of these were transplanted. During this period only 5 patients (7%) died awaiting OLT. Of 33 patients treated at the University of Chicago, 5 received RLT. Donor: recipient weight ratios ranged from 2:1 to 8.1:1. For RLT median operative blood loss was 1.7 blood volumes (range 0.5-11.7) with an operative time of 9.3 + 3.5 hr. Acceptable early graft function was observed in five patients, all of whom were discharged from the hospital. Four of these five patients are alive between 2 and 48 months after transplantation. Marginal graft function with cholestasis and coagulopathy was associated with acute intracranial hemorrhage and neurologic death in one case. One patient died intraoperatively with non-function caused by the use of a liver from a donor with steatosis and a poor size match. Another patient died on day 5 with primary nonfunction and persistent hemorrhage. Systemic cytomegalovirus infection was the cause of death in the other two cases. RLT can provide life-sustaining liver function in urgent clinical settings. The graft can serve as a temporary or permanent liver replacement. With evolution of the technique RLT could eventually be offered to more elective candidates and increase the utilization of available donors by reducing size limitations in OLT.