You are in: eMedicine Specialties > Pediatrics: Surgery > Transplantation Split Liver TransplantationArticle Last Updated: Jul 10, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: David A Axelrod, MD, MBA, Assistant Professor of Surgery, Section Chief, Solid Organ Transplantation, Dartmouth-Hitchcock Medical Center David A Axelrod is a member of the following medical societies: American College of Surgeons, American Society of Transplant Surgeons, and New Hampshire Medical Society Coauthor(s): John C Magee, MD, Director of Pediatric Transplantation, Associate Professor of Surgery, Department of Transplant Surgery, University of Michigan Hospital Editors: Casimir F Firlit, MD, PhD, Consulting Staff, Department of Urology, Cardinal Glennon Children's Hospital; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Steve Dunn, MD, Chief, Solid Organ Transplantation, Department of Surgery, Alfred I DuPont Hospital for Children at Wilmington; Ron Shapiro, MD, Professor of Surgery, University of Pittsburgh; Director, Kidney, Pancreas, and Islet Transplantation, Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center; Stuart M Greenstein, MD, Professor of Surgery, Albert Einstein College of Medicine; Consulting Surgeon, Department of Surgery, Division of Transplantation, Montefiore Medical Center Author and Editor Disclosure Synonyms and related keywords: split liver transplantation, SLT, SPLIT, split-liver transplantation, split liver, liver transplantation, liver transplant, LT, orthotopic liver transplant, orthotopic liver transplantation, OLT, organ transplant, organ transplantation, hepatology, ascites, encephalopathy, cirrhosis, United Network for Organ Sharing, UNOS, liver donor, organ donor, rejection, reduced-size liver transplantation, living-donor liver transplantation, cadaveric donors INTRODUCTIONSection 2 of 11
  The need for liver transplants currently far eclipses the supply of available donor organs. According to 2005 statistics from the United Network for Organ Sharing (UNOS), the waiting list for a liver transplant now exceeds 17,000 patients. Despite considerable efforts to increase the supply of available deceased donor organs, the number of deceased donor liver transplants has been fairly constant at 5000 livers per year. As a result, many patients continue to die while awaiting a life-saving transplant. The shortage of available organs was previously most acute for pediatric patients. Because of the small number of pediatric donors, the mortality rate among patients on the wait list was commonly high when only whole-organ transplantation was performed (Emond, 1990). In 1984, the introduction of reduced-liver transplant in which a portion of the adult liver was given to infants and children dramatically reduced this mortality rate. Over the past 20 years, the risk of death among patients on the pediatric weight list has substantially declined because of the ability to use these reduced-size grafts and because of the subsequent introduction of live-donor transplantation, As most commonly performed, split-liver transplantation (SLT) involves the division of donor liver from a deceased adult between a pediatric recipient and an adult recipient to maximize the benefit of each available donor organ. For excellent patient education resources, visit eMedicine's Liver, Gallbladder, and Pancreas Center and Hepatitis Center. Also, see eMedicine's patient education articles, Cirrhosis and Liver Transplant. History of the ProcedureGiven the high wait-list mortality rate among pediatric patients with end-stage liver disease and our improved understanding of segmental liver anatomy, a variety of techniques were developed to provide reduced-size allografts with complete arterial, portal, biliary, and venous drainage. Although SLT was initially used for the pediatric population receiving deceased-donor grafts, the lessons learned from SLT have been successfully applied to live-donor liver transplantation to benefit pediatric and adult recipients (Kim 2004). In 1984, Bismuth and colleagues reported successful transplantation of a reduced-size liver in which only a portion of the donor organ was used and the remaining liver discarded. In reduced-size liver transplantation, the liver allograft can be tailored to the recipient's size by using a variety of functional lobes or segments. The graft most commonly used in pediatric patients includes the left lateral segments (segments 2 and 3) and the left lobe (segments 2-4). The right lobe (segments 4-8) is rarely used in pediatric patients because it does not offer notable size advantages over whole livers. Although this technique was successful in increasing the number of pediatric transplants, it did not increase the total number of organs available for transplantation. In 1990, Strong reported the first successful living-related liver transplantation for pediatric recipients utilizing the left lateral segment from a mother to her son. Broelsch and colleagues (1991) subsequently reported outcomes in 20 children receiving left lateral segments from adult living donors. Patient survival was 85%. Since these initial experiences, live-donor transplantation has been expanded to adult recipients and is currently the subject of a large multicenter trial by the National Institutes of Health (NIH), ie, the Adult To Adult Living Donor Liver Donor Liver Transplantation Cohort Study (A2ALL). Advantages of living-donor liver transplantation include the selection of an ideal donor, the ability to schedule the case electively, the maximal time to prepare the recipient, and the relatively short cold ischemia time. Although living-donor transplantation increases the number of livers available for pediatric and adult recipients, donor safety remains a major concern. Several donor deaths were highly publicized. Although the exact risks remain uncertain, serious donor morbidity and mortality are possible. Ethical issues, such as those regarding donor coercion and informed consent, raise concerns about application of this technique in both urgent and elective settings. SLT takes advantage of the knowledge gained in reduced-liver transplantation to increase the organ supply by using the right lobe or trisegmental graft that remains after the left lateral segment or left lobe is removed for a pediatric recipient. In 1998, Pichlmayr et al described the technical approach to SLT, including preservation of arterial, biliary, venous drainage for both grafts. Broelsch reported the first large series in 1990, though the results were initially poor, hampering widespread acceptance of this technique (Bismuth, 1989; Shaw, 1990; Emond, 1990). Early series had higher-than-expected rates of primary nonfunction and biliary complications that substantially reduced recipient survival. Ethical questions were also raised about the potential of disadvantaging adult recipients to provide grafts for pediatric patients. In the past 10 years, refinements in surgical techniques and improved organ preservation have improved patient survival rates. Particularly in the case of right trisegment–left lateral segment splits, adult recipients can expect results that approach those of patients who receive transplants from standard deceased donors (Azoulay, 1996; Kalayoglu, 1996; Rogiers, 1996; Goss, 1997; Rela, 1998, Washburn 2005). The success of SLT in children has led some authors to argue that live-donor transplantation is no longer necessary in the pediatric population (Gridelli, 2003). Overall, the transplantation community has endorsed the expanded use of SLT as a technique to increase the organ supply and to reduce wait-list mortality rates (Emond, 2002). ProblemThe etiology of end-stage organ disease is the subject of several other chapters. However, several specific comments are relevant to patients undergoing SLT. For pediatric patients, biliary atresia remains the most common indication for liver transplantation, followed by fulminant hepatic failure, metabolic diseases, and a variety of other causes including cholestatic diseases and malignancy (hepatoblastoma). Given the preponderance of childhood transplantation for biliary atresia, a considerable number children undergoing transplantation are younger than 2 years and, therefore, excellent candidates for a left lateral segment graft from a split liver. Older children require larger grafts, including left-lobe grafts which have increased rates of graft loss and complications, though the increase may reflect differences in recipients' characteristics and their underlying illnesses (Axelrod, 2005). The etiologies of liver disease in adult recipients of SLTs do not notably differ from those receiving whole-organ grafts. Initial concerns regarding the potential for increased recurrence of hepatitis C in regenerating allografts have not been validated in the literature (Humar, 2005). SLT has now been applied in all patient groups, including status 1 patients and patients requiring retransplantation (Washburn. 2005). FrequencyIn the young pediatric population, SLT or reduced-liver transplantation has become an increasingly frequent procedure. In a recent review of 755 patients undergoing transplantation for biliary atresia, only 44% received whole-organ grafts. Deceased-donor variants (reduced or split) represented 31% of grafts, whereas live donors provided the remaining 24% (Utterson, 2005). In the adult population, SLT remains infrequent. Among patients receiving a transplant from a deceased donor allograft in 2002-2005, SLT was performed in only 2.9% of the total population. However, this percentage does appear to be increasing over time. INDICATIONSSection 3 of 11
SLT has traditionally been restricted to ideal deceased donors. Although the exact definition of ideal donors remains controversial, the following characteristics are used to exclude donors from consideration according to the Organ Procurement and Transplantation Pediatric Subcommittee:
In a recent study from the University of California at Los Angeles (UCLA) in 110 patients, the length of donor hospital stay, the donor's sodium level, and prolonged warm ischemia were donor- and procedure-dependent risk factors for poor outcome after SLT (Ghobrial, 2000). In addition, a suitable pediatric recipient must be available for the left lateral segment or left lobe. RELEVANT ANATOMYSection 4 of 11
The goal of SLT is to produce 2 grafts with preserved vascular supply (ie, portal vein, hepatic artery), venous drainage, and bile duct. Anatomic variations (replaced arteries, biliary anomalies) are not considered to be a contraindication to liver splitting as long as both right- and left-sided allografts have a complete set of vessels and biliary drainage. In most cases, the vena cava and the common bile duct are maintained with the right-sided allograft, and the left hepatic vein and left bile duct are divided for the left allograft. For left-lobe grafts, the middle and left hepatic veins are preserved. In these cases, the surgeon transplanting the right-lobe graft should recognize and either preserve or reconstruct the large veins in segment 5, which frequently drain in the middle hepatic vein. The main portal vein and the main arterial supply can be maintained with either side depending on the anatomy and who was designated the primary recipient of the allograft. CONTRAINDICATIONSSection 5 of 11
Hemodynamically instability of the donor is a contraindicated for SLT. Donors staying in the hospital for longer then 5 days and those with liver function results exceeding 3 times the mean should not be considered for splitting. Anatomically aberrant hepatic arterial anatomy is not a contraindication to splitting as long as the arterial supply to each of the segmental grafts is not compromised WORKUPSection 6 of 11
Lab Studies
Imaging Studies
Diagnostic Procedures
Histologic FindingsThe presence of macrosteatosis in the liver biopsy sample increases the risk of primary nonfunction and injury due to ischemia reperfusion injury. Macrosteatosis is identified as large vesicles with the cytoplasm of the hepatocytes. TREATMENTSection 7 of 11
Surgical therapyTwo approaches are available to generate split liver allografts: ex vivo, in which the organ is removed from the donor and divided on the back table after the organ has been flushed and cooled, and in situ, in which the dissection and parenchymal division is performed in the donor while the organs are still being perfused. In situ splitting has the advantage of avoiding prolonged cold ischemia time and rewarming during the bench procedure for ex vivo splitting. Obtaining hemostasis of the cut surfaces in the donor and assessment of the quality and viability of both grafts (especially segment 4) are additional advantages with this approach. The disadvantage of in situ splitting is the additional 1-2 hours that are added to a standard multiorgan procedure at the donor hospital. Cooperation between different surgical teams is crucial, and the decision to proceed to in situ splitting should be based on the stability of the donor's condition and on the conditions of all waiting recipients. In general, acceptable outcomes can be achieved by using either approach. Intraoperative detailsEx vivo technique In the ex vivo split-liver technique, the whole organ is retrieved and preserved according to the standard techniques of multiple organ procurement. Donor surgeons must recognize and preserve aberrant arterial supply and biliary drainage. In addition, additional donor arteries and veins should be recovered to provide material for vascular reconstruction if needed. Grafts are prepared at the recipient transplant center and placed in an ice bath containing preservation solution. In some centers, predissection cholangiography and arteriography are performed to delineate the anatomy precisely. As an alternative, a coronary dilator or feeding tube can used to probe the hepatic artery and bile ducts. Dissection of the portal triad is performed to separate the branches of the hepatic artery, the portal vein, and the right and left hepatic bile ducts. In general, the common bile duct is retained with the right graft unless a left-lobe split is being performed. In that case, the duct is usually retained with the primary recipient to whom the organ was first allocated. Division of the arterial and portal supply is ideally the result of close collaboration among recipient surgeons. The rationale for determining which graft receives the major vascular pedicle is determined by the anatomy of the components of the porta hepatis. In most cases, the left portal vein and the right hepatic artery are sectioned because they are long and thus facilitate anastomoses to the recipient vessels. Interposition grafts consisting of an allogeneic iliac, splenic, or superior mesenteric artery and the iliac vein have been used as extensions for both right- and left-lobe grafts. The line of parenchymal transection for a left-lateral segment split extends from the confluence of the middle and left hepatic veins to approximately 0.5-1 cm to the right of the umbilical fissure and up to the hilar plate. This division can be performed by using the clamp-crush method, an ultrasonic dissector (Cavitron ultrasonic surgical aspirator [CUSA]; Tyco Healthcare, Mansfield, MA), or a water-jet instrument (Hydrojet; Erbe, Tubingen, Germany). Large biliary radicals and vascular structures must be controlled with sutures or hemostatic clips. The left hepatic vein is retained with the left-sided graft, and the right and middle hepatic veins in continuity with the vena cava are retained with the right graft. The cut surfaces of the grafts are often sealed with fibrin glue, collagen, or polyglactin 910 mesh to reduce bleeding. In situ technique In situ splitting is based on the techniques established for living-donor procurement that is practiced in the heart-beating deceased donor. Rogiers and colleagues first described in situ splitting in 1995, and they reported a low incidence of biliary complications and intra-abdominal hemorrhage. The initial step is to obtain control of the supraceliac and infrarenal aorta, as well as the inferior mesenteric vein, for those who elect to perform a portal flush, to permit rapid multiorgan cooling in the event of donor instability. If the anatomy and appearance of the liver are suitable, segments 2 and 3 of the liver are mobilized as in living-donor procurement. The hepatic arterial anatomy is identified. The left portal vein is dissected with ligation of the branches to the caudate lobe and segment 4. Extrahepatic isolation of the left hepatic vein is accomplished with care to ensure that drainage through the middle hepatic vein is not compromised. Transection of the parenchyma is performed in a line 0.5-1 cm to the right of the umbilical fissure as described for ex vivo splitting. Electrocautery and suture ligation are used as needed. The left hilar plate and bile ducts are sharply divided with scissors so as not to devascularize the ducts. On completion of the dissection, 2 liver grafts are obtained, each with its own vascular pedicle and venous drainage. The procurement proceeds in a standard fashion with perfusion of the abdominal organs with University of Wisconsin (UW) solution. After perfusion, the liver is procured in the usual manner, and the vascular attachments between each graft are divided. The common bile duct and the main portal vein are usually retained with the right graft. The main arterial supply may be kept in either side. Several groups have raised concerns regarding the viability of segments 1 and 4 after liver splitting ex vivo or in situ. Opinions regarding the need to resect segments 1 and 4 from the right graft because of devascularization vary, ranging from always recommended to never recommended (Goss, 1997; Rela, 1998). Perfusion of these segments is easiest to assess during in situ splitting because the procedure is performed in a heart-beating donor. However, in both ex vivo and in situ splitting, segment 4 hypoperfusion is a potential pitfall and may require treatment with segmentectomy after reperfusion in the recipient. Transplantation of the split liver Implantation of the right split liver into an adult is accomplished in the same manner as a standard orthotopic liver transplantation (OLT) with either preservation or excision of the recipient cava. Biliary reconstruction is usually done by means of a choledochocholedochostomy if the main duct is preserved, with or without a T tube. The left graft is transplanted into a child or a small adult by using a piggyback technique with preservation of the recipient's vena cava. The left hepatic vein is anastomosed to the suprahepatic cava of the patient. Portal vein reconstruction is individualized to the recipient's anatomy. In some cases, a vein graft is needed to prevent tension-free anastomosis, but this is not routinely recommended. Reconstruction of the hepatic artery depends on whether the celiac trunk is retained with the graft. If the main arterial supply is maintained with the left graft, the celiac trunk is anastomosed to the recipient's common hepatic artery. If the left hepatic artery is divided, reconstruction by using the recipient's hepatic artery is preferred, such as that described in living-related transplantation. The left hepatic bile duct is uniformly anastomosed to a Roux-en-Y limb. Separate ducts to segments 2 and 3 may require 2 different anastomoses to the same Roux-en-Y limb. Postoperative detailsVigilance is vital in the postoperative period after SLT. Compared with transplantation with standard donor livers, SLT has an increased incidence of primary nonfunction, hemorrhage, biloma, and biliary strictures. The overall retransplantation rate after SLT is 13% for adults split livers versus 7% for standard donors (Merion, 2004). Follow-upIn general, posttransplantational care does not differ for split recipients compared with standard donors. Dosages of immunosuppressants may be decreased to improve regeneration, though data regarding the need for such a practice is lacking. In general, patients can be expected to recover well and leave the hospital promptly. COMPLICATIONSSection 8 of 11
Complications after SLT are similar to those of whole-organ liver transplantation. The rate of bile leaks may be slighted elevated because of the large cut surface, particularly in livers that are split into right and left lobes. Otherwise, the rate of delayed graft function and allograft -nonfunction is not increased in properly selected split-liver grafts. One complication that occurs more frequently with split grafts is small-for-size syndrome (SFSS). SFSS is associated with grafts that are less than 0.8% of the recipient's total body weight. In clinical practice, patients have a spectrum of abnormalities, which range from isolated hyperbilirubinemia to irreversible graft failure leading to the patient's death or retransplantation. The pathophysiology remains unclear, but is likely related to outflow obstruction, arterial hypoperfusion, or portal venous hyperperfusion. OUTCOME AND PROGNOSISSection 9 of 11
Initial results after SLT were disappointing (Bismuth, 1989; Shaw, 1990; Emond, 1990). Overall patient survival and graft survival were reduced, and surgical complications were increased in patients who underwent SLT. However, because of technical refinements and appropriate selection of recipients, results of ex vivo and in situ SLT both are nearly equivalent to those expected with whole organs (Busuttil, 2005; Washburn, 2005,) Recent series reported by Washburn et al (2005) demonstrated survival among adult patients and graft survival after right trisegmental splits were equivalent to survival after whole-organ transplantation (87.1% and 85.5%, respectively, at 1 year). In the largest single-center series reported to date (>3000 liver transplants), Busuttil and colleagues (2005) demonstrated comparable outcomes between whole-liver transplants and other types of grafts. However, the experience in large centers may not be completely generalizable to other settings. In their recent analysis of the risk of graft failure, Feng et al (2006) reported a significant increase in the risk of graft failure associated with split grafts when the entire database of the Organ Procurement and Transplantation Network (OPTN) was reviewed. In addition, Merion et al (2001) reported that the need for retransplantation was higher in recipients of split-liver grafts than in recipients of whole-liver grafts. Centers performing in situ splitting techniques have also reported successful results with low rates of biliary and bleeding complications. In the series that Rogiers et al reported (1995), 6-month patient survival and graft survival rates after in situ SLT were 92.8% and 85.7%, respectively, without any biliary complications. Goss and colleagues (1997) reported a 92% patient survival rate and an 86% graft survival rate, with a 3% rate of biliary complications in 28 patients. Results for pediatric patient remain a subject of contention. Single-center series have demonstrated excellent results with deceased-donor left lateral segment grafts. Lee et al (2005) reported 82% graft survival at 1 and 3 years. Overall patient survival was 90%. Large, multi-institutional series, including reports for the Studies of Pediatric Liver Transplantation (SPLIT) research group continue to show that deceased donor split livers are associated with an increased risk of graft failure (Utterson, 2005). Finally, Roberts et al (2004) analyzed data from UNOS and a scientific registry of transplant recipients and determined that living-donor livers were associated with improved graft and patient survival in children younger than 2 years. The association was reversed in the older pediatric and adolescent population. Outcomes after a liver is split for 2 adult recipients have been reported. The left lateral segment can be transplanted into a small adult. As an alternative, to overcome small-for-size graft problems, the liver can be split through the midplane, resulting in a full left lobe and a right lobe. Sommacale et al (2000) reported using the midplane and retaining the middle hepatic vein with the left-sided graft, while Gundlach and colleagues (2000) reported longitudinally splitting the inferior vena cava for venous reconstruction. In both reports, the midplane was used for bipartitioning of the liver, resulting a full left lobe liver; the outcomes were successful. Most recently, Azoulay et al (2001) reported ex vivo splitting of the liver through segment 4 for 2 adults; results were comparable to those of whole-organ grafts in 34 patients. Axelrod et al (2005) reported the results of SLTs in adolescents and found reduced survival among patients receiving a left-lobe graft. The effect of liver splitting on waiting times for transplantation has the potential to be substantial. In Brousse's experience, the number of transplantable grafts was increased by 28% (Azoulay, 1996). Investigators from the Hamburg group, King's College, and UCLA have reported improved use and transplant efficiency (Rogiers, 1995; Goss, 1997; Rela, 1998). Maximal use of SLT would provide enough grafts to treat most patients on the pediatric waiting list. Merion and colleagues (2004) demonstrated that splitting all available livers for whom there was an appropriate pediatric recipient would help 59 additional recipients for every 100 livers split, even after they accounted for the slightly increased need for retransplantation. In this analysis, splitting of 100 livers was associated with a net increment of 11 life-years compared with continued time on the waiting list. FUTURE AND CONTROVERSIESSection 10 of 11
Expansion of the use of split livers involves increasing cooperation between centers and expanding institutional experience with these techniques. Most successful experiences have been in a single center; however, the distribution of expertise is also likely to evolve with growing needs for transplantation. In addition, research is needed to best understand liver function in small grafts and to ensure regeneration in the early period after transplantation. This research will be beneficial in expanding the applications of SLT and living-donor liver transplantation. Technical details of the splitting procedure and vascular reconstruction of the grafts are challenging, but they should not be obstacles to the further improvement of this procedure. With the current donor-safety issues that still surround living-donor transplantation, SLT offers a compelling strategy to increase the donor supply. REFERENCESSection 11 of 11
Split Liver Transplantation excerpt Article Last Updated: Jul 10, 2006 |
