Split Liver Transplantation Treatment & Management

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 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.

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.^[23]

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, 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.^{[14, 15]} 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.

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.^[24]

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 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.

Initial results after split-liver transplantation (SLT) were disappointing.^{[9, 10, 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.^{[25, 16]}

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).^[16]

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.^[25] 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.^[26] 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.^[24]

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.^[23] 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.^[14]

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%.^[27] 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.^[21] 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.^[28]

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,^[29] while Gundlach et al (2000) reported longitudinally splitting the inferior vena cava for venous reconstruction.^[30] 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 2 adults; results were comparable to those of whole-organ grafts in 34 patients.^[31] Axelrod et al (2005) reported the results of split-liver transplantations in adolescents and found reduced survival among patients receiving a left-lobe graft.^[19]

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%.^[11] Investigators from the Hamburg group, King's College, and UCLA have reported improved use and transplant efficiency.^{[23, 14, 15]} 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.^[24]

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.