Split Liver Transplantation 

Updated: Jan 18, 2017
Author: Jonathan P Roach, MD; Chief Editor: Stuart M Greenstein, MD 

Overview

Practice Essentials

The need for liver transplants currently far eclipses the supply of available donor organs. According to the Organ Procurement and Transplantation Network, as of January 2017, 14,450 patients were awaiting a liver transplant .[1] Despite considerable efforts to increase the supply of available organs from deceased donors, the total number of liver transplants has remained fairly constant at 6200-6400 liver transplants per year over the last 10 years. 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.[2] Reduced-liver transplant, in which infants and children receive a portion of the adult liver, was introduced in 1984. Over the following 30 years, the risk of death among patients on the pediatric wait list substantially declined because of the ability to use these reduced-size grafts and because of the subsequent introduction of live-donor transplantation.[3]

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. However, living-donor partial liver griafts are also used.

For patient education information, see the Digestive Disorders Center and Infections Center, as well as Cirrhosis and Liver Transplant.

History of the Procedure

Given the high wait-list mortality rate among pediatric patients with end-stage liver disease and improved understanding of segmental liver anatomy, various techniques were developed to provide reduced-size allografts with complete arterial, portal, biliary, and venous drainage. Although split-liver transplantation was initially used for deceased-donor grafts in the pediatric population, the lessons learned from split-liver transplantation have been successfully applied to live-donor liver transplantation to benefit both pediatric and adult recipients.[4]

In 1984, Bismuth and Houssin reported successful transplantation of a reduced-size liver in which only a portion of the donor organ was used and the remaining liver discarded.[5] In reduced-size liver transplantation, the liver allograft can be tailored to the recipient's size by using various 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 et al reported the first successful living-related liver transplantation for a pediatric recipient, utilizing the left lateral segment from a mother to her son.[6] Broelsch and colleagues (1991) subsequently reported outcomes in 20 children receiving left lateral segments from adult living donors. Patient survival was 85%.[7]

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), the Adult To Adult Living Donor Liver Donor Liver Transplantation Cohort Study (A2ALL). Advantages of living-donor liver transplantation include the following:

  • Selection of an ideal donor

  • Ability to schedule the case electively

  • Maximal time to prepare the recipient

  • 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.

Split-liver transplantation 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 1988, Pichlmayr et al described the technical approach to split-liver transplantation, including preservation of arterial, biliary, venous drainage for both grafts.[8] Broelsch reported the first large series in 1990,[9] although the results were initially poor, hampering widespread acceptance of this technique.[10, 11, 2]

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 two decades, 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 standard deceased-donor transplants.[12, 13, 14, 15, 16, 17, 18]

The success of split-liver transplantation in children has led some authors to argue that live-donor transplantation is no longer necessary in the pediatric population.[19] Overall, the transplantation community has endorsed the expanded use of split-liver transplantation as a technique to increase the organ supply and to reduce wait-list mortality rates.[20, 21]

Problem

The etiology of end-stage liver disease is the subject of several other Medscape articles. However, several specific comments are relevant to patients undergoing split-liver transplantation.

For pediatric patients, biliary atresia remains the most common indication for liver transplantation, followed by fulminant hepatic failure, metabolic diseases, and various other causes, including cholestatic diseases and malignancy (hepatoblastoma). Given the preponderance of childhood transplantation for biliary atresia, a considerable number of 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, although the increase may reflect differences in recipients' characteristics and their underlying illnesses.[22]

The etiologies of liver disease in adult recipients of split-liver transplantations 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.[23] Split-liver transplantation has now been applied in all patient groups, including status 1 patients and patients requiring retransplantation.[17]

Epidemiology

Frequency

In the young pediatric population, split-liver transplantation or reduced-liver transplantation has become an increasingly frequent procedure. In a 2005 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%.[24]

More recently, a European center reported that only 21% of patients with biliary atresia who received a liver transplant received a whole organ, while 21% received a reduced-size liver, 11% received a split liver and 47% received a liver graft from a live donor.[25]

In the adult population, split-liver transplantation remains infrequent. Among patients receiving a transplant from a deceased donor allograft in 2002-2005, split-liver transplantation was performed in only 2.9% of the total population. However, this percentage does appear to be increasing over time.

Indications

Split-liver transplantation (SLT) has traditionally been restricted to organs from ideal deceased donors. Although the exact definition of ideal donors remains controversial, the Organ Procurement and Transplantation Network (OPTN) identifies a liver as one with the potential to be split if the donor meets all the following criteria[26] :

  • Age younger than 40 years
  • Use of a single vasopressor or less
  • Transaminases no greater than three times the normal level
  • Body mass index (BMI) 28 kg/m 2 or less

However, while those criteria are met by more than 10% of all deceased donors, and more than 20% of donors younger than 35 years, less than 1.5% of all donor livers have been split since the OPTN adopted those criteria in 2007.[26]

The following characteristics are used to exclude donors from consideration, according to the OPTN Pediatric Subcommittee:

  • Age younger than 10 years or older than 40 years

  • History of cancer or insulin-dependent diabetes mellitus

  • Infection with HIV, hepatitis B virus, or hepatitis C virus

  • Use of both dopamine and dobutamine

  • Serum bilirubin value of more than 3 mg/dL

  • Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) level greater than 150 U/L

  • Cardiac arrest after neurologic event leading to brain death

  • Serum sodium level of more than 170 mEq/L

In addition, a suitable pediatric recipient must be available for the left lateral segment or left lobe.

Relevant Anatomy

The goal of split-liver transplantation (SLT) is to produce two 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 into the middle hepatic vein. The main portal vein and the main arterial supply can be maintained with either side, depending on the anatomy and the designated primary recipient of the allograft.

For more information about the relevant anatomy, see Liver Anatomy.

Contraindications

Hemodynamic instability of the donor is a contraindication for split-liver transplantation. Donors staying in the hospital for longer than 5 days and those with liver function results exceeding three 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.

 

Workup

Laboratory Studies

The usual laboratory tests for a multiorgan deceased donor candidate are required, including the following:

  • Blood typing

  • Blood count

  • Arterial blood gas analysis

  • Basic metabolic panel

  • Liver function tests

  • Hepatitis and HIV serology

In addition, blood cultures may be obtained to rule out infection in donor candidates who have undergone prolonged hospitalization.

Patients with positive serologic results for hepatitis or HIV are excluded from split-liver transplantation (SLT). However, organs positive for hepatitis C can be used for whole-organ transplantation.

Liver function test results are required to be less than three times the reference-range values. Livers with questionable fatty infiltration should be examined with biopsy and not be used for splitting if clinically significant fatty infiltration is found.

Imaging Studies

No specific imaging studies are required for splitting the liver beyond the usual deceased multiorgan donor workup. Studies that may be required in the workup for living donors, such as Doppler ultrasonography, angiography, magnetic resonance cholangiography, or endoscopic retrograde cholangiopancreatography (ERCP), are not required, and the anatomy of the liver is identified during surgical dissection in the operating room.

Diagnostic Procedures

No diagnostic procedures are routinely performed for split-liver transplantations. When the degree of steatosis is questionable, percutaneous liver biopsy may be performed before organ recovery. Similarly, open liver biopsy can be performed at the time of recovery should the liver unexpectedly appear abnormal.

Histologic Findings

The 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.

 

Treatment

Surgical Therapy

Two 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 organ is 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 with either approach.[27]

Intraoperative Details

Ex 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 precisely delineate the anatomy. 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.[28]

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.

Upon completion of the dissection, two 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.[15, 16] 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 Details

Vigilance is vital in the postoperative period after split-liver transplantation (SLT). Compared with transplantation with standard donor livers, split-liver transplantation has an increased incidence of primary nonfunction, hemorrhage, biloma, and biliary strictures. The overall retransplantation rate after split-liver transplantation is 13% for adults split livers versus 7% for standard donors.[29]

Follow-up

In general, posttransplantational care does not differ for split recipients compared with standard donors. Dosages of immunosuppressants may be decreased to improve regeneration, although data regarding the need for such a practice are lacking. In general, patients can be expected to recover well and leave the hospital promptly.

Complications

Complications after split-liver transplantation (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 Prognosis

Initial results after split-liver transplantation (SLT) were disappointing.[10, 11, 2] Overall patient survival and graft survival were reduced, and surgical complications were increased in patients who underwent split-liver transplantation. However, because of technical refinements and appropriate selection of recipients, results of ex vivo and in situ split-liver transplantation both are nearly equivalent to those expected with whole organs.[30, 17, 31, 32, 33]

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).[17]

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.[30] However, the experience in large centers may not be completely generalizable to other settings.

In their 2006 analysis of the risk of graft failure, Feng et al 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.[34] 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.[29]

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 split-liver transplantation were 92.8% and 85.7%, respectively, without any biliary complications.[28] 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.[15]

Pediatric recipients

Results in pediatric patients 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%.[35] 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.[24] Using the SPLIT registry, Englesbe et al completed a survey of current practices and offer a six-step approach for a model to improve transplantation initiatives.[36]

In a single-center study by Doyle et al (2013), results of split-liver transplants were equivalent to those of whole-organ transplantation. In the 30 pediatric recipients of split liver grafts,  1-, 5-, and 10-year overall rates were 96.7%, 80.0%, and 80.0%, respectively, while 1-, 5-, and 10-year graft survival rates were 93.3%, 76.8, and 76.8%, respectively.[37]

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.[38]

Two adult recipients

Outcomes after a liver is split for two 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,[39] while Gundlach et al (2000) reported longitudinally splitting the inferior vena cava for venous reconstruction.[40] In both reports, the midplane was used for bipartitioning of the liver, resulting a full left lobe liver; the outcomes were successful.

In 2001, Azoulay et al reported ex vivo splitting of the liver through segment 4 for two adults; results were comparable to those of whole-organ grafts in 34 patients.[41] Axelrod et al (2005) reported the results of split-liver transplantations in adolescents and found reduced survival among patients receiving a left-lobe graft.[22]

A 2014 retrospective review by Hashimoto et al of 25 lobar grafts (10 left lobes and 15 right lobes) for adult-sized recipients determined that the 5-year graft survival for hemilivers was comparable to whole livers (80.0% vs. 81.5%, P = 0.43). In 92% of donors, the livers were split in situ. Hemiliver recipients did experience biliary complications more frequently (32.0% vs. 10.7%, P = 0.01).[42]

 

Waiting time reduction

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%.[12] Investigators from the Hamburg group, King's College, and UCLA have reported improved use and transplant efficiency.[28, 15, 16]

Maximal use of split-liver transplantation 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.[29]

Future and Controversies

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 split-liver transplantation (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, split-liver transplantation offers a compelling strategy to increase the donor supply.