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Split Liver Transplantation for Two Adult Recipients
CHAPTER 53
Split Liver Transplantation for Two Adult Recipients Mark L. Sturdevant • Abhinav Humar
CHAPTER OUTLINE SELECTION CRITERIA
COMPLICATIONS
Donor Recipient
Vascular Complications Biliary Complications Small-for-Size Syndrome
SURGICAL TECHNIQUE Donor Recipient Right Lobe Graft Left Lobe Graft
UNANSWERED QUESTIONS
RESULTS
SUMMARY
Orthotopic liver transplantation has now become the gold standard treatment for end-stage liver disease. However, the ongoing shortage of suitable livers, together with progressively longer waiting lists, prevents many patients from being transplanted; this has led to a significant waiting list mortality rate at most centers. Using livers from living donors is one way to increase the supply of liver grafts but carries with it the disadvantage of donor risk. Splitting the deceased donor liver to use for two recipients represents another method for expanding the donor pool. With split-liver transplantation (SLT), a whole liver from a deceased donor is divided into two functioning grafts, which can then be transplanted into two appropriate-sized recipients. The first SLT was performed by Pichlmayr et al in 1988.1 Subsequently several centers published their SLT series. The technical aspects of SLT are in many ways similar to the technical aspects of living donor transplants, and these two areas of liver transplantation have developed side by side in many centers, with one program complementing the other. More recently, living donor transplantation has become significantly more common than SLT, especially in areas of the world where deceased donor transplants are not common. The two techniques to expand the donor pool are not mutually exclusive and in fact are usually more successful in programs where both live donor and deceased donor SLT procedures are performed. Ultimately the ability to offer all options for transplant can only benefit the potential recipient and minimize waiting list mortality. The vast majority of SLT procedures performed to date have been for one adult and one pediatric recipient. 702
Ethics of Splitting Allocation Split Potential
Usually the liver is split into a smaller portion consisting of the left lateral segment (which can be transplanted into a pediatric recipient) and the remaining larger extended right lobe (which can be transplanted into a normal-sized adult recipient). The benefits for pediatric recipients have been tremendous, including an expansion of the donor pool and a significant decrease in waiting times and mortality rates.2,3 As experience with SLT in this setting has grown, the results have improved. Many single-center series now report equivalent outcomes with split and whole organ deceased donor transplants. Although splitting the liver for an adult and a pediatric recipient has had a significant impact on the expansion of the donor pool for pediatric recipients, it has had no impact on the donor pool for adult recipients, because ultimately this type of split generates only one graft for the adult recipient. Because the majority of individuals on a transplant list are adults, and the majority of waiting list deaths are in adult patients, SLT can have the maximal impact on waiting list mortality if the two grafts generated can be used for two adult recipients. To accomplish this, the liver is generally split into the anatomical right and left lobes, which are then transplanted into two adult-sized recipients. However, splitting the liver for two adult recipients is generally uncommon at this time. There are many reasons why SLT for two adult recipients has remained relatively uncommon. Ideal donors appropriate for splitting have become less common as an increasing number of deceased donors have risk factors that would make them unsuitable for splitting. Similarly, with current allocation rules, appropriate recipients may also be difficult to find because the potential recipients at the top of a waiting list
53 Split Liver Transplantation for Two Adult Recipients
may be too ill to tolerate a partial liver transplant. Other hurdles include the technical complexities and challenges associated with the procedure, the logistics involved with coordinating multiple teams, and the reported results to date. Nonetheless, SLT can play a role in the expansion of the donor pool for adult recipients. Key aspects in trying to optimize results include careful donor and recipient selection, meticulous surgical technique in both the donor and recipient operations, and appropriate methods of allocation to ensure the greatest chance of success. This chapter will cover these areas and present some of the published series with regard to patient outcomes.
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Cold ischemic time should be minimized as much as possible in all SLT recipients. This is a crucial aspect because cold ischemic time represents one of the few donor risk factors that can be affected by the transplant team. Ideally cold ischemic times should be less than 10 hours, and less than 8 hours if possible. This requires significant planning with multiple teams and operating rooms so that there can be some degree of overlap between the donor and recipient procedures and at least some degree of overlap between the two recipient procedures.
Recipient SELECTION CRITERIA Proper donor and recipient selection are crucial to ensuring a good outcome with any SLT. Donors generally have to be ideal; but equally important, suitable recipients that can tolerate partial grafts must be chosen. One obviously wants to prevent the situation in which one deceased donor liver that would have worked in one recipient is split and results in two grafts that do not work in two recipients.
Donor Donors should be medically ideal to minimize the risks of primary nonfunction, especially for recipients of the smaller left lobe graft. Young, hemodynamically stable donors with near-normal liver function test results, short intensive care unit stay (<5 days), and absent or fairly short arrest times should be selected; with such donors, primary nonfunction for the recipients should be uncommon. The upper donor age limit for splitting a liver is unclear, and the criteria likely need to be more stringent when performing a right lobe/left lobe split versus an extended right/left lateral lobe split. Generally donors much beyond an upper age limit of 45 years are likely not to be suitable for splitting. Liver function test results should be close to normal or at most less than three times the upper limit of normal. Donor size plays an important role in determining suitability for right lobe/left lobe splits because the size of the grafts generated in this situation are key predictors of successful outcome in the recipients. The size of the donor correlates to some extent with the size of the liver because we know that the liver constitutes roughly 2% of the total body weight. This obviously holds true only to a certain weight, and obese donors (body mass index > 30) should generally not be considered because of the risk for underlying fatty liver. An intraoperative biopsy can be useful to rule out any significant macrosteatosis, and greater than 10% fat would be a contraindication for splitting the liver. Male donors are generally likely to be more suitable for splitting because their livers tend to be bigger, but this cannot always be reliably predicted. Many donors have a computed tomography scan of the abdomen available (especially if the cause of death was trauma), and it is generally not difficult now to obtain at least crude measures of liver volumes from these scans before donation to help in making an appropriate selection decision.
When selecting appropriate recipients for SLT, important issues are graft size requirement, cause of liver failure, and severity of illness. Critically ill patients with severe portal hypertension and high Model for End-Stage Liver Disease (MELD) scores are generally not good candidates for partial grafts, especially from a deceased donor.4 Patients with tumors, metabolic diseases, or MELD scores below 30 may be appropriate candidates for these types of splits. Hepatitis C in the recipient does not represent a contraindication for a split graft.5 A graft weight–to–body weight ratio (GWBWR) of close to 0.8% should likely be the minimum when selecting appropriate recipients. Results with GWBWR ratios of less than 0.8% have been associated with inferior results, though not all series have supported this finding.6 It is also important to remember that this recommendation is based on data mostly from the living donor literature. A partial graft from a deceased donor likely has more injury than a partial graft from a living donor. Additional stresses on the deceased donor versus the living donor graft include the factors that led initially to the donor’s death, potential hemodynamic instability during the preprocurement management of the deceased donor, and the subsequent cold ischemic time after removal of the organ. Therefore extrapolating the 0.8% value may not be entirely appropriate for SLT from a deceased donor. Nonetheless, our practice has been to try to select recipients in whom we know the GWBWR will exceed 0.8%. This can sometimes be difficult because estimating the size of the partial graft ahead of time can be difficult. Again, there may be an abdominal computed tomography scan available on the donor for review before the procurement. This can be valuable in assessing the anatomy and the size of the two grafts ahead of the procurement. The final decision regarding which recipient is most appropriate can be made intraoperatively during the procurement surgery, once the donor liver has been carefully inspected and the size of the grafts estimated by a trained surgeon. Another important aspect of the recipient selection process is adequately informing the potential recipient of the splitting procedure and obtaining informed consent. With the current organ allocation system in the United States, the graft is initially assigned to a primary recipient. If the liver is to be split, the second recipient is chosen at the discretion of the center performing the split. This is advantageous for the second recipient, who then bypasses additional waiting time. For primary recipients,
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however, there is no significant advantage: we are in fact asking them to give a part of “their” new liver to someone else. If the primary recipient is to receive the left lobe (and is therefore likely of smaller size), the issue is not as difficult. A full-size liver graft from a large donor may be difficult to fit into this recipient. Performing the split may allow for a better size match in this situation. But if the primary recipient is to receive the right lobe, the issue is more difficult, because such recipients could easily accommodate the whole graft. In our experience there is usually no hesitation on the part of the recipients to participate in the split, and in some instances some recipients have commented that they tremendously appreciated the opportunity to help another individual by agreeing to the split. Nonetheless, with the present allocation rules, it is crucial to fully inform potential recipients about splitting and to obtain informed consent. This brings up an important question, which is if it is up to the primary recipient to decide if a split should be performed by virtue of their consent. Ideally the center and organ procurement organization should decide ahead of time if this is an appropriate organ for spitting, and the two partial grafts then should be allocated to the two most appropriate recipients near the top of the list, but not necessarily at the very top of the list. These points have been debated for years, and unfortunately there is no good consensus on this at present.
FIGURE 53-1 n Full right lobe/left lobe split with preservation of the middle hepatic vein with the left lobe graft and the cava with the right lobe graft. The common artery and portal vein are preserved with the left lobe graft, but the bile duct is preserved with the right lobe graft.
SURGICAL TECHNIQUE The SLT procedure can be divided into two parts: the donor operation and the recipient surgery (which in turn consists of the surgery for the right lobe and left lobe recipients). Both parts of the procedure are technically demanding, and the success of this procedure rests on performing a meticulous division of the donor liver and then subsequent implantation in the two recipients. When the liver is to be split for two adult recipients, it is usually transected in its midplane, generating two similarsized grafts—the larger anatomical right lobe and the smaller anatomical left lobe. The transection plane should stay to the right of the middle hepatic vein so that this structure is retained with the left lobe (Fig. 53-1). Segment IV makes up a crucial part of the left lobe, and hence the middle hepatic vein should be preserved with the left lobe to ensure no congestion. Loss of the middle hepatic vein may affect drainage of segments V and VIII in the right lobe graft. If significant draining vessels are identified, they can easily be reconstructed on the back table using vascular conduits from the deceased donor. Regarding the dissection in the hilum (Fig. 53-2), our preference has been to leave the full length of the hilar vascular structures intact with the left lobe. The rightsided hilar structures are usually larger than the left-sided structures. Therefore leaving the main vessels intact with the left lobe makes that transplant easier. The common bile duct is left maintained with the right lobe graft, however, so that there is a greater chance of having a single bile duct orifice to reconstruct on both the right and left lobe grafts. One crucial technical point for the recipient operation is ensuring adequate venous outflow of the
FIGURE 53-2 n Hilar dissection demonstrating takedown of the left hilar plate and encircling of the left hilar plate. The line of transection is marked (dashed black line). The common duct is maintained with the right lobe graft, but the main hepatic artery and portal vein are maintained with the left lobe graft.
grafts to prevent congestion. Preserving the cava with the right lobe graft helps to maximize outflow by preserving all inferior hepatic veins. This also allows for back-table reconstruction of any segment V and VIII veins draining from the right lobe to the middle hepatic vein.
Donor No standard operative technique yet exists for such splitting of livers; each center has developed its own technique, with subtle variations. The majority of these techniques involve dividing the liver in its midplane, thereby generating two grafts consisting of the anatomical right lobe (segments V, VI, VII, VIII) and the anatomical left lobe (segments I, II, III, IV). The middle hepatic vein and left hepatic vein are preserved with the left lobe graft, as are the main trunks of the hepatic arterial and portal venous systems. The donor operation begins with a careful examination of the liver to assess quality, size, and anatomy. An
53 Split Liver Transplantation for Two Adult Recipients
intraoperative cholangiogram is an easy test to obtain that can give useful information about the anatomy of the biliary tree. The right lobe is not mobilized, and all short hepatic veins draining the posterior aspect of the right lobe into the inferior vena cava (IVC) are thus preserved. The left lobe (including the caudate lobe) is completely mobilized away from the underlying IVC. The confluence of the left and middle hepatic veins is encircled with an umbilical tape. The plan is to preserve the IVC with the right lobe graft and the middle hepatic vein with the left lobe graft. By preserving the donor IVC with the right lobe, all short hepatic veins (small and large) draining the right lobe are kept intact. Also, major hepatic vein tributaries to the middle hepatic vein tributaries can be reconstructed on the back table in cold preservative solution. Doing so maximizes outflow from the right lobe, minimizes warm ischemic time, and simplifies implantation of the right lobe. The porta hepatis is then carefully examined to evaluate the hepatic arterial anatomy. Regarding the dissection in the porta, our preference has been to leave the full length of the main vascular structures intact with the left lobe (i.e., the common hepatic artery with the celiac trunk and the main portal vein, see Fig. 53-2). The right lobe then retains just the right-sided vascular structures: the right hepatic artery and the right portal vein. The right-sided hilar structures are usually larger than the left-sided vascular structures. Therefore leaving the main vessels intact with the left lobe makes that transplant easier. The inflow blood supply to the right lobe (arterial and portal) is isolated. The intraoperative cholangiogram can help guide the biliary dissection by giving valuable information regarding the biliary anatomy. Given the long extrahepatic course of the left hepatic duct, the common bile duct is maintained with the right lobe graft; the point of transection of the bile duct is at the junction of the left hepatic duct with the common hepatic duct so that there is a greater chance of having a single bile duct orifice to reconstruct on both the right and left lobe grafts. It is useful to divide the common bile duct just above the duodenum and pass a biliary probe through the cut end proximally to help decide on the exact site for transection of the biliary system between the two lobes. The final step is transection of the hepatic parenchyma itself. The transection plane should stay to the right of the middle hepatic vein, so that this vein is retained with the left lobe (Fig. 53-3). The transection can be performed in situ, using a device such as a Cavitron Ultrasonic Surgical Aspirator (CUSA), or ex situ after the liver is removed. Our preference is in situ splitting, which has several advantages over the ex situ technique. First, it decreases the total cold ischemic time. Performing the split on the back table could add up to 2 to 3 hours of cold ischemia. Also, there is likely some warming of the liver on the back table, even if the split is being performed in a cold ice bath of preservative solution. Even a warming of the liver by a few degrees may have a negative impact on the outcome. Performing the split in situ also has other advantages. Significantly less bleeding occurs when the organs are reperfused. The two liver grafts can be assessed in the donor immediately
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FIGURE 53-3 n The line of transection on the hepatic parenchyma is just to the right of the middle hepatic vein.
FIGURE 53-4 n The completed split in situ, which allows one to examine the two lobes to ensure that there are no areas of devascularization and also helps to minimize cold ischemia time.
after parenchymal transection and before vascular interruption, to ensure no significant ischemia at the borders of the cut edge of the liver (Fig. 53-4). Previous SLT series have shown superior results with in situ versus ex situ liver splits.7,8 For all these reasons we feel that the actual splitting of the donor liver should be performed in situ. Disadvantages of the in situ procedure include the time added to the procurement during the parenchymal transection and the potential for hemodynamic instability in the donor if there is any significant bleeding. This can affect not only the liver itself but also the other organs that are being removed during the procurement. Once the transection is complete, the liver and other abdominal organs are flushed with cold preservative solution as usual and the liver is removed. On the back table the previously isolated vasculature to the right lobe is divided to completely separate the two grafts. Any important hepatic venous tributaries from the right lobe draining into the middle hepatic vein (segment V or VIII) that had been divided during the parenchymal
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FIGURE 53-5 n The split is completed on the back table by final division of the vascular structures. Important middle hepatic vein tributaries of the right lobe can be reconstructed using conduit from the donor.
HA HA CBD
A
PV
Roux limb
B
PV
FIGURE 53-6 n The right lobe (A) and left lobe (B) can then be implanted in the respective recipients. The left lobe is done in a piggyback fashion. The right lobe can be either caval replacement (as shown) or piggyback. CBD, Common bile duct; HA, hepatic artery; PV, portal vein.
transection can now be reconstructed. This can be done by using vascular conduit from the deceased donor and anastomosing the cut surface veins to the preserved donor IVC using vascular conduit (such as iliac vein) from the deceased donor (Fig. 53-5). The preceding description is our preferred technique, but several variations have been described. Two important ones include the cava splitting method and the middle hepatic vein splitting technique. In the cava splitting method the left lobe is not mobilized from the IVC. Rather the cava is split down the middle on the back table, thus preserving a portion of it as a patch with both the right and left lobes.9 This technique has the advantage of preserving all of the outflow of the left lobe, including the short hepatic veins. The middle hepatic vein splitting technique involves ex situ transection of the hepatic parenchyma with division of the middle hepatic vein longitudinally along its length. This can then be reconstructed in both the right and left lobe grafts using a vein patch, hence preserving the middle
hepatic vein with both lobes and maximizing outflow for both grafts.10
Recipient (Figure 53-6) Right Lobe Graft The deceased donor SLT right lobe graft is implanted in a manner similar to that used for a right lobe living donor graft. The diseased liver in the recipient is removed, and the IVC can be either preserved or removed. If the IVC has been preserved with the right lobe graft, either a caval replacement, piggyback, or side-to-side cavaplasty technique can be used for outflow reconstruction. Ensuring adequate outflow of the right graft is crucial. The donor right portal vein is then sewn to the recipient right or common portal vein (depending on which is the better size match). The donor right hepatic artery is sewn to the recipient right hepatic artery. Biliary reconstruction is then
53 Split Liver Transplantation for Two Adult Recipients
performed either with a duct-to-duct technique or with a Roux-en-Y hepaticojejunostomy. Left Lobe Graft The left lobe is implanted in a standard piggyback fashion with preservation of the recipient’s IVC. The donor hepatic veins can be anastomosed to the recipient’s left and middle hepatic vein confluence with good size match. The remainder of the vascular connections are done in a standard fashion.
RESULTS The initial series of adult/pediatric SLT until the mid1990s demonstrated poor recipient and graft survival of 50%.11,12 However, by the mid-1990s reports from the European Split Liver Registry showed 6-month patient and graft survival similar to whole-liver transplant.13 Single-center North American series, as well as analyses of registry data, similarly demonstrated improving outcomes with SLT for adult/pediatric recipients. Data on outcomes for SLT for two adults is significantly less robust, with mostly small single-center series or case reports in the literature, highlighting the infrequency of these procedures. No registry reports for SLT for two adult recipients have been reported. The American Society of Transplant Surgeons (ASTS) survey performed between April 2000 and May 2001 elicited a response from 83 of 89 surgical teams identified from the annual report of the Scientific Registry of Transplant Recipients as having performed at least one SLT procedure during the previous year. Thirty-six of the responding teams reported data on 207 left lateral segment, 152 right trisegment, and only 15 left lobe, and 13 right lobe grafts.14 Therefore left and right lobe graft data from the ASTS survey do not permit meaningful analysis. Nonetheless, the reported overall incidence of left lobe complications was 26% versus 22% for right lobe grafts, with the majority used for urgent recipients. Biliary complications were most frequent, with vascular complications reported in 4% of left lobe versus 9% of right lobe grafts. Primary nonfunction and graft failure were 7% and 9% for left lobe versus 9% and 14% for right lobe grafts, respectively. Recipient death was observed in 7% of left versus 8% of right lobe grafts. Single-center reports from Europe, North America, and Asia, even though each is relatively small in size, have provided more meaningful data on outcomes after these procedures. Azoulay et al15 reported their outcomes of transplantation with right and left split-liver grafts and also compared with those of whole-liver transplants. For whole-liver, right and left split-liver grafts, respectively, patient survival rates were 88%, 74%, and 88% at 1 year and 85%, 74%, and 64% at 2 years. Graft survival rates were 88%, 74%, and 75% at 1 year and 85%, 74%, and 43% at 2 years. Patient survival was adversely affected by graft steatosis and recipient’s inpatient status before transplantation. Graft survival was adversely affected by steatosis and a GWBWR of less than 1%. Primary nonfunction occurred in three left split-liver grafts. The rates of arterial (6%) and biliary (22%) complications were
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similar to published data from conventional transplantation for an adult and a child. SLT for two adults increased the number of recipients compared with whole-liver transplantation and was logistically possible in 16 of the 104 (15%) optimal cadaver donors. Humar et al16 reported their experience of in situ splitting of livers from six cadaver donors and transplanted into 12 adult recipients at the University of Minnesota. The patient and graft survival were 80% each, and arterial and biliary complications occurred in 16% and 25% of recipients, respectively. Analysis of the split-liver transplantation data suggested a time-dependent learning curve, which was applicable to surgical splitting technique, implantation, and recipient selection. Not all single-center reports have been positive, with some reporting a high incidence of complications and graft loss. One center in Italy recently reported on 16 adult patients who underwent SLT using 9 full right lobe grafts (segments V to VIII) and 7 full left lobe grafts (segments I to IV).17 The splitting procedure was always carried out in situ with a fully perfused liver. Postoperative complications were recorded in 8 (50%) patients: 5 right lobe recipients and 3 left lobe recipients. No one was retransplanted. After a median follow-up of 55.82 months (range, 0.4 to 91.2), 5 (31%) patients died, and the 1-, 3-, and 5-year overall survival rate for patients and grafts was 69%, leading the authors to question whether SLT for two adult recipients should even be performed. However, other single-center reports from the same area have had more positive results. Cescon et al18 reported on 22 adult patients receiving SLT and demonstrated good results. Overall patient and graft survival were 90% and 86%. Patient survival was 84% in recipients of right grafts and 100% in recipients of left grafts. Graft survival was 84% and 89%, respectively.
COMPLICATIONS Complications after SLT are generally similar to those that may occur after any type of transplant, though the overall incidence of certain types of complications may differ. In addition, there are some conditions unique to partial lobe transplants and generally not seen with whole-liver transplants that can contribute to complications. An example of this is the cut surface of the liver present on both the left and right lobe grafts, which may be an additional source of complications such as bleeding or bile leak. Overall, given the technically demanding nature of the procedure and the partial nature of the graft, surgical complications tend to be more common after SLT compared to whole-liver transplants, though published reports suggest it is similar to the reported incidence of complications after live donor transplants.
Vascular Complications The incidence of vascular complications after whole-liver transplantation is 5% to 10% and is likely to be at least twice that in SLT recipients. Thrombosis is the most common early event; stenosis, dissection, and pseudoaneurysm formation are less common. Any of the vascular
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anastomoses (hepatic artery, portal vein, and hepatic vein) may be involved, but the hepatic artery is most common. Hepatic artery thrombosis has a reported incidence of 5% to 10%, higher than reported in whole-liver transplantation, likely because of the smaller caliber of vessels and the sometimes complex arterial reconstruction required. Thrombosis of the portal vein is less frequent (compared with the hepatic artery) but again is likely more common than in whole-organ recipients. Complications of the hepatic veins (such as thrombosis and stenosis) are uncommon but again have a higher incidence in the partial grafts. The risk for problems may be higher in recipients of the left lobe graft because the segment may be quite mobile, and if it is not properly aligned, it may twist on the anastomosis, obstructing flow. Presentation is usually with massive ascites and graft dysfunction. Ultrasound Doppler examination will usually demonstrate this, as well as the other early vascular problems, and some form of routine monitoring is warranted to aid in early diagnosis.
Biliary Complications Complications of the biliary system continue to be the most common type of surgical complication after SLT. The incidence is 20% to 40% with an associated mortality of less than 5%. Biliary complications manifest as either a leak or an obstruction. Timing often determines type and clinical outcome of the complication. Bile leaks tend to occur early postoperatively and often require surgical repair, whereas obstruction usually occurs later and can often be managed with radiological or endoscopic techniques. Most bile leaks occur within the first 30 days after transplantation and can be from the anastomotic site or the cut surface of the liver. The area around the anastomosis has the most tenuous blood supply: both the donor common bile duct (CBD) and the recipient portion of the CBD are supplied by end arteries. Excessive dissection or cauterization around the donor or recipient CBD can further disrupt the blood supply, leading to ischemic complications. Another important cause of biliary tract complications is hepatic artery thrombosis: the donor CBD receives its blood supply from the hepatic artery. With any biliary tract complication the hepatic artery should be carefully assessed to document patency. Other causes of leaks include poorly placed sutures, excessive number of sutures, and tension on the anastomosis. With partial transplants the cut surface of the liver represents an important site for a bile leak. Careful parenchymal transection can help to lower the incidence. The in situ technique of liver transection can also help to minimize the risk for cut surface bile leaks. Biliary obstruction is usually secondary to stricture and occurs later in the postoperative period. It is most common at the anastomotic site and is likely related to local ischemia. Nonanastomotic strictures usually have a worse prognosis; they are associated with hepatic artery thrombosis or prolonged cold ischemic times. The treatment is usually not operative, but rather by percutaneous or endoscopic interventions. If these initial options fail, surgical revision is required.
Small-for-Size Syndrome Small-for-size syndrome (SFSS) has emerged as an interesting and significant problem that is fairly unique to partial liver transplants. SFSS and injury related to the use of small-for-size grafts were reported initially by Emond et al.19 Although there is no uniform consensus on the definition of SFSS, the diagnosis is generally based on persistent hyperbilirubinemia and massive ascites during the posttransplant subacute phase without evidence of any other cause. The incidence is reportedly close to 10%, though the exact incidence is unknown because the definition of this condition is not agreed upon. Multiple risk factors have been identified, including the size of the graft, the type of graft, the degree of portal hypertension, and the spleen size. Of these, the degree of portal hypertension and portal perfusion is likely most important. The pathophysiological characteristics of the condition are believed to be related to damage to hepatocytes and vasculature secondary to portal shear stress. Portal hyperperfusion leads to poor hepatic arterial inflow because of the arterial buffer response, which ultimately leads to hepatic necrosis and poor hepatic regeneration.20 In the absence of any intervention, SFSS is associated with a significant mortality early after transplant, with many of the patients succumbing to complications associated with poor graft function, such as infections and multiorgan failure. With increased understanding of the concept of small for size, strategies to prevent SFSS and strategies to rescue small-for-size grafts are being developed (Table 53-1).
UNANSWERED QUESTIONS Ethics of Splitting Surgical complications are more common in SLT (versus whole graft) recipients, related to the cut surface of TABLE 53-1 M echanisms and Possible Methods of Avoiding or Treating Small-for-Size Syndrome Mechanism of Small for Size Prevention strategies
Suboptimal graft quality Insufficient graft volume Impaired venous outflow
Treatment strategies
Increased portal flow or pressure
Strategies Younger donor, nonfatty liver, decreased ischemia time Adequate graft volume (GWBWR ideally should be ≥0.8%) Wide venous anastomosis, reconstruction of segmental drainage Portosystemic shunt, splenectomy, splenic artery ligation, medical therapies (e.g., octreotide)
GWBWR, Graft weight–to–body weight ratio.
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the liver, smaller vessels for anastomosis, and more complicated biliary reconstruction. Therefore one important aspect of the recipient selection process is adequately informing the potential recipient of the splitting procedure and obtaining informed consent. Who makes the decision of whether a liver should be split at the present time? The question of how much role the recipient plays in the decision to split the liver is unclear.
Allocation How best to allocate a liver for splitting is completely undecided at the present time and varies from country to country and from region to region. Should the liver from an ideal donor be preferentially allocated for a split procedure, and if so, how does this affect the sickest patients at the top of a waiting list who may be too sick for a partial liver transplant? Not all centers may have the technical expertise or personnel to perform splits—should ideal livers be preferentially allocated to centers that have such expertise and personnel available?
Split Potential More data are needed to better define donor and recipient selection criteria, which are crucial to success. It is difficult to estimate how much impact adult SLT will have on the donor pool. About 25% of all deceased donors in the United States are between 15 and 35 years of age. If even half of these livers could be used for splits, the number of liver transplants could potentially increase by 10%, or by close to 500. With better preservation techniques, more livers may be amenable to splitting. In the near future this technique will likely become part of every major liver transplant center's repertoire in order to provide the maximum advantage for their candidates on the waiting list.
SUMMARY Given proper donor and recipient selection, SLT can be successfully applied for two adult recipients. Donors should be “ideal,” (i.e., young, large, and hemodynamically stable with normal liver function test results). Careful evaluation of the donor hepatic artery and biliary anatomy intraoperatively is essential to helping decide if the split is technically possible. The split itself may be performed ex situ or in situ, but the latter method helps to minimize graft ischemia. Recipients should not be critically ill; careful attention should be paid to the size, especially for left lobe graft recipients. Further experience will help to better define the limits of this procedure and improve results. At present this represents a technique that can help to expand the donor pool in a limited number of circumstances, but there is a potential for growth.
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Pearls and Pitfalls • Paramount to the success of split-liver transplantation is proper donor and recipient selection. • Split procedures can be performed in situ or ex situ; the in situ technique reduces cold ischemia, enhances identification of biliary and vascular structures, and reduces hemorrhage upon graft reperfusion. • Cold ischemia time can have a significant impact on the outcomes, and every effort should be made to minimize cold ischemia time, especially in the left lobe graft recipient. • The right lobe of the split usually has more outflow issues, whereas the left lobe has more size issues. • Meticulous attention to technical detail is crucial for ensuring successful outcomes in this technically challenging procedure.
REFERENCES 1. Pichlmayr R, Ringe B, Gubernatis G, et al. Transplantation of a donor liver to 2 recipients (splitting transplantation)–a new method in the further development of segmental liver transplantation. Langenbecks Arch Chir. 1988;373:127-130. 2. Busuttil RW, Goss JA. Split liver transplantation. Ann Surg. 1999;229:313-321. 3. Goss JA, Yersiz H, Shackleton CR, et al. In situ splitting of the cadaveric liver for transplantation. Transplantation. 1997;64: 871-877. 4. Lee KW, Cameron AM, Maley WR, et al. Factors affecting graft survival after adult/child split-liver transplantation: analysis of the UNOS/OPTN data base. Am J Transplant. 2008;8:1186-1196. 5. Humar A, Horn K, Kalis A, et al. Living donor and split-liver transplants in Hepatitis C recipients: does liver regeneration increase the risk for recurrence? Am J Transplant. 2005 Feb;5(2):399-405. 6. Hill MJ, Hughes M, Jie T, et al. Graft Weight/Recipient weight ratio- how well does it predict outcome after partial liver transplant? Liver Transpl. 2009;15(9):1056. 7. Goss JA, Yersiz H, Shackleton CR, et al. In situ splitting of the cadaveric liver for transplantation. Transplantation. 1997;64: 871-877. 8. 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. 9. Gundlach M, Broering D, Topp S, et al. Split-cava technique: liver splitting for two adult recipients. Liver Transpl. 2000 Nov;6(6): 703-706. 10. 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 Mar;11(3):350-352. 11. 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 Jul;212(1):14-22. 12. 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. 13. de Ville de Goyet J. Split liver transplantation in Europe–1988 to 1993. Transplantation. 1995;59:1371-1376. 14. Renz JF, Emond JC, Yersiz H, et al. Split-liver transplantation in the United States: outcomes of a national survey. Ann Surg. 2004; 239:172-181. 15. 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.
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16. Humar A, Ramcharan T, Sielaff TD, et al. Split liver transplantation for two adult recipients: an initial experience. Am J Transplant. 2001;1:366-372. 17. Alessandro G, Andrea L, Matteo D, et al. Should we still offer split-level transplantation for two adult recipients? A retrospective study of our experience. Liver Transpl. 2008;14:999-1006. 18. Cescon M, Grazi GL, Ravaioli M, et al. Conventional split liver transplantation for two adult recipients: a recent experience in a single European center. Transplantation. 2009;88:1117.
19. Goldstein MJ, Salame E, Kapur S, et al. Analysis of failure in living donor liver transplantation: differential outcomes in children and adults. World J Surg. 2003;27(3):356-364. 20. Demetris AJ, Kelly DM, Eghtesad B, et al. Pathophysiologic observations and histopathologic recognition of the portal hyperperfusion or small-for-size syndrome. Am J Surg Pathol. 2006;30:986-993.
Split Liver Transplantation for Two Adult Recipients Mark L. Sturdevant • Abhinav Humar
CHAPTER OUTLINE SELECTION CRITERIA
COMPLICATIONS
Donor Recipient
Vascular Complications Biliary Complications Small-for-Size Syndrome
SURGICAL TECHNIQUE Donor Recipient Right Lobe Graft Left Lobe Graft
UNANSWERED QUESTIONS
RESULTS
SUMMARY
Orthotopic liver transplantation has now become the gold standard treatment for end-stage liver disease. However, the ongoing shortage of suitable livers, together with progressively longer waiting lists, prevents many patients from being transplanted; this has led to a significant waiting list mortality rate at most centers. Using livers from living donors is one way to increase the supply of liver grafts but carries with it the disadvantage of donor risk. Splitting the deceased donor liver to use for two recipients represents another method for expanding the donor pool. With split-liver transplantation (SLT), a whole liver from a deceased donor is divided into two functioning grafts, which can then be transplanted into two appropriate-sized recipients. The first SLT was performed by Pichlmayr et al in 1988.1 Subsequently several centers published their SLT series. The technical aspects of SLT are in many ways similar to the technical aspects of living donor transplants, and these two areas of liver transplantation have developed side by side in many centers, with one program complementing the other. More recently, living donor transplantation has become significantly more common than SLT, especially in areas of the world where deceased donor transplants are not common. The two techniques to expand the donor pool are not mutually exclusive and in fact are usually more successful in programs where both live donor and deceased donor SLT procedures are performed. Ultimately the ability to offer all options for transplant can only benefit the potential recipient and minimize waiting list mortality. The vast majority of SLT procedures performed to date have been for one adult and one pediatric recipient. 702
Ethics of Splitting Allocation Split Potential
Usually the liver is split into a smaller portion consisting of the left lateral segment (which can be transplanted into a pediatric recipient) and the remaining larger extended right lobe (which can be transplanted into a normal-sized adult recipient). The benefits for pediatric recipients have been tremendous, including an expansion of the donor pool and a significant decrease in waiting times and mortality rates.2,3 As experience with SLT in this setting has grown, the results have improved. Many single-center series now report equivalent outcomes with split and whole organ deceased donor transplants. Although splitting the liver for an adult and a pediatric recipient has had a significant impact on the expansion of the donor pool for pediatric recipients, it has had no impact on the donor pool for adult recipients, because ultimately this type of split generates only one graft for the adult recipient. Because the majority of individuals on a transplant list are adults, and the majority of waiting list deaths are in adult patients, SLT can have the maximal impact on waiting list mortality if the two grafts generated can be used for two adult recipients. To accomplish this, the liver is generally split into the anatomical right and left lobes, which are then transplanted into two adult-sized recipients. However, splitting the liver for two adult recipients is generally uncommon at this time. There are many reasons why SLT for two adult recipients has remained relatively uncommon. Ideal donors appropriate for splitting have become less common as an increasing number of deceased donors have risk factors that would make them unsuitable for splitting. Similarly, with current allocation rules, appropriate recipients may also be difficult to find because the potential recipients at the top of a waiting list
53 Split Liver Transplantation for Two Adult Recipients
may be too ill to tolerate a partial liver transplant. Other hurdles include the technical complexities and challenges associated with the procedure, the logistics involved with coordinating multiple teams, and the reported results to date. Nonetheless, SLT can play a role in the expansion of the donor pool for adult recipients. Key aspects in trying to optimize results include careful donor and recipient selection, meticulous surgical technique in both the donor and recipient operations, and appropriate methods of allocation to ensure the greatest chance of success. This chapter will cover these areas and present some of the published series with regard to patient outcomes.
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Cold ischemic time should be minimized as much as possible in all SLT recipients. This is a crucial aspect because cold ischemic time represents one of the few donor risk factors that can be affected by the transplant team. Ideally cold ischemic times should be less than 10 hours, and less than 8 hours if possible. This requires significant planning with multiple teams and operating rooms so that there can be some degree of overlap between the donor and recipient procedures and at least some degree of overlap between the two recipient procedures.
Recipient SELECTION CRITERIA Proper donor and recipient selection are crucial to ensuring a good outcome with any SLT. Donors generally have to be ideal; but equally important, suitable recipients that can tolerate partial grafts must be chosen. One obviously wants to prevent the situation in which one deceased donor liver that would have worked in one recipient is split and results in two grafts that do not work in two recipients.
Donor Donors should be medically ideal to minimize the risks of primary nonfunction, especially for recipients of the smaller left lobe graft. Young, hemodynamically stable donors with near-normal liver function test results, short intensive care unit stay (<5 days), and absent or fairly short arrest times should be selected; with such donors, primary nonfunction for the recipients should be uncommon. The upper donor age limit for splitting a liver is unclear, and the criteria likely need to be more stringent when performing a right lobe/left lobe split versus an extended right/left lateral lobe split. Generally donors much beyond an upper age limit of 45 years are likely not to be suitable for splitting. Liver function test results should be close to normal or at most less than three times the upper limit of normal. Donor size plays an important role in determining suitability for right lobe/left lobe splits because the size of the grafts generated in this situation are key predictors of successful outcome in the recipients. The size of the donor correlates to some extent with the size of the liver because we know that the liver constitutes roughly 2% of the total body weight. This obviously holds true only to a certain weight, and obese donors (body mass index > 30) should generally not be considered because of the risk for underlying fatty liver. An intraoperative biopsy can be useful to rule out any significant macrosteatosis, and greater than 10% fat would be a contraindication for splitting the liver. Male donors are generally likely to be more suitable for splitting because their livers tend to be bigger, but this cannot always be reliably predicted. Many donors have a computed tomography scan of the abdomen available (especially if the cause of death was trauma), and it is generally not difficult now to obtain at least crude measures of liver volumes from these scans before donation to help in making an appropriate selection decision.
When selecting appropriate recipients for SLT, important issues are graft size requirement, cause of liver failure, and severity of illness. Critically ill patients with severe portal hypertension and high Model for End-Stage Liver Disease (MELD) scores are generally not good candidates for partial grafts, especially from a deceased donor.4 Patients with tumors, metabolic diseases, or MELD scores below 30 may be appropriate candidates for these types of splits. Hepatitis C in the recipient does not represent a contraindication for a split graft.5 A graft weight–to–body weight ratio (GWBWR) of close to 0.8% should likely be the minimum when selecting appropriate recipients. Results with GWBWR ratios of less than 0.8% have been associated with inferior results, though not all series have supported this finding.6 It is also important to remember that this recommendation is based on data mostly from the living donor literature. A partial graft from a deceased donor likely has more injury than a partial graft from a living donor. Additional stresses on the deceased donor versus the living donor graft include the factors that led initially to the donor’s death, potential hemodynamic instability during the preprocurement management of the deceased donor, and the subsequent cold ischemic time after removal of the organ. Therefore extrapolating the 0.8% value may not be entirely appropriate for SLT from a deceased donor. Nonetheless, our practice has been to try to select recipients in whom we know the GWBWR will exceed 0.8%. This can sometimes be difficult because estimating the size of the partial graft ahead of time can be difficult. Again, there may be an abdominal computed tomography scan available on the donor for review before the procurement. This can be valuable in assessing the anatomy and the size of the two grafts ahead of the procurement. The final decision regarding which recipient is most appropriate can be made intraoperatively during the procurement surgery, once the donor liver has been carefully inspected and the size of the grafts estimated by a trained surgeon. Another important aspect of the recipient selection process is adequately informing the potential recipient of the splitting procedure and obtaining informed consent. With the current organ allocation system in the United States, the graft is initially assigned to a primary recipient. If the liver is to be split, the second recipient is chosen at the discretion of the center performing the split. This is advantageous for the second recipient, who then bypasses additional waiting time. For primary recipients,
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however, there is no significant advantage: we are in fact asking them to give a part of “their” new liver to someone else. If the primary recipient is to receive the left lobe (and is therefore likely of smaller size), the issue is not as difficult. A full-size liver graft from a large donor may be difficult to fit into this recipient. Performing the split may allow for a better size match in this situation. But if the primary recipient is to receive the right lobe, the issue is more difficult, because such recipients could easily accommodate the whole graft. In our experience there is usually no hesitation on the part of the recipients to participate in the split, and in some instances some recipients have commented that they tremendously appreciated the opportunity to help another individual by agreeing to the split. Nonetheless, with the present allocation rules, it is crucial to fully inform potential recipients about splitting and to obtain informed consent. This brings up an important question, which is if it is up to the primary recipient to decide if a split should be performed by virtue of their consent. Ideally the center and organ procurement organization should decide ahead of time if this is an appropriate organ for spitting, and the two partial grafts then should be allocated to the two most appropriate recipients near the top of the list, but not necessarily at the very top of the list. These points have been debated for years, and unfortunately there is no good consensus on this at present.
FIGURE 53-1 n Full right lobe/left lobe split with preservation of the middle hepatic vein with the left lobe graft and the cava with the right lobe graft. The common artery and portal vein are preserved with the left lobe graft, but the bile duct is preserved with the right lobe graft.
SURGICAL TECHNIQUE The SLT procedure can be divided into two parts: the donor operation and the recipient surgery (which in turn consists of the surgery for the right lobe and left lobe recipients). Both parts of the procedure are technically demanding, and the success of this procedure rests on performing a meticulous division of the donor liver and then subsequent implantation in the two recipients. When the liver is to be split for two adult recipients, it is usually transected in its midplane, generating two similarsized grafts—the larger anatomical right lobe and the smaller anatomical left lobe. The transection plane should stay to the right of the middle hepatic vein so that this structure is retained with the left lobe (Fig. 53-1). Segment IV makes up a crucial part of the left lobe, and hence the middle hepatic vein should be preserved with the left lobe to ensure no congestion. Loss of the middle hepatic vein may affect drainage of segments V and VIII in the right lobe graft. If significant draining vessels are identified, they can easily be reconstructed on the back table using vascular conduits from the deceased donor. Regarding the dissection in the hilum (Fig. 53-2), our preference has been to leave the full length of the hilar vascular structures intact with the left lobe. The rightsided hilar structures are usually larger than the left-sided structures. Therefore leaving the main vessels intact with the left lobe makes that transplant easier. The common bile duct is left maintained with the right lobe graft, however, so that there is a greater chance of having a single bile duct orifice to reconstruct on both the right and left lobe grafts. One crucial technical point for the recipient operation is ensuring adequate venous outflow of the
FIGURE 53-2 n Hilar dissection demonstrating takedown of the left hilar plate and encircling of the left hilar plate. The line of transection is marked (dashed black line). The common duct is maintained with the right lobe graft, but the main hepatic artery and portal vein are maintained with the left lobe graft.
grafts to prevent congestion. Preserving the cava with the right lobe graft helps to maximize outflow by preserving all inferior hepatic veins. This also allows for back-table reconstruction of any segment V and VIII veins draining from the right lobe to the middle hepatic vein.
Donor No standard operative technique yet exists for such splitting of livers; each center has developed its own technique, with subtle variations. The majority of these techniques involve dividing the liver in its midplane, thereby generating two grafts consisting of the anatomical right lobe (segments V, VI, VII, VIII) and the anatomical left lobe (segments I, II, III, IV). The middle hepatic vein and left hepatic vein are preserved with the left lobe graft, as are the main trunks of the hepatic arterial and portal venous systems. The donor operation begins with a careful examination of the liver to assess quality, size, and anatomy. An
53 Split Liver Transplantation for Two Adult Recipients
intraoperative cholangiogram is an easy test to obtain that can give useful information about the anatomy of the biliary tree. The right lobe is not mobilized, and all short hepatic veins draining the posterior aspect of the right lobe into the inferior vena cava (IVC) are thus preserved. The left lobe (including the caudate lobe) is completely mobilized away from the underlying IVC. The confluence of the left and middle hepatic veins is encircled with an umbilical tape. The plan is to preserve the IVC with the right lobe graft and the middle hepatic vein with the left lobe graft. By preserving the donor IVC with the right lobe, all short hepatic veins (small and large) draining the right lobe are kept intact. Also, major hepatic vein tributaries to the middle hepatic vein tributaries can be reconstructed on the back table in cold preservative solution. Doing so maximizes outflow from the right lobe, minimizes warm ischemic time, and simplifies implantation of the right lobe. The porta hepatis is then carefully examined to evaluate the hepatic arterial anatomy. Regarding the dissection in the porta, our preference has been to leave the full length of the main vascular structures intact with the left lobe (i.e., the common hepatic artery with the celiac trunk and the main portal vein, see Fig. 53-2). The right lobe then retains just the right-sided vascular structures: the right hepatic artery and the right portal vein. The right-sided hilar structures are usually larger than the left-sided vascular structures. Therefore leaving the main vessels intact with the left lobe makes that transplant easier. The inflow blood supply to the right lobe (arterial and portal) is isolated. The intraoperative cholangiogram can help guide the biliary dissection by giving valuable information regarding the biliary anatomy. Given the long extrahepatic course of the left hepatic duct, the common bile duct is maintained with the right lobe graft; the point of transection of the bile duct is at the junction of the left hepatic duct with the common hepatic duct so that there is a greater chance of having a single bile duct orifice to reconstruct on both the right and left lobe grafts. It is useful to divide the common bile duct just above the duodenum and pass a biliary probe through the cut end proximally to help decide on the exact site for transection of the biliary system between the two lobes. The final step is transection of the hepatic parenchyma itself. The transection plane should stay to the right of the middle hepatic vein, so that this vein is retained with the left lobe (Fig. 53-3). The transection can be performed in situ, using a device such as a Cavitron Ultrasonic Surgical Aspirator (CUSA), or ex situ after the liver is removed. Our preference is in situ splitting, which has several advantages over the ex situ technique. First, it decreases the total cold ischemic time. Performing the split on the back table could add up to 2 to 3 hours of cold ischemia. Also, there is likely some warming of the liver on the back table, even if the split is being performed in a cold ice bath of preservative solution. Even a warming of the liver by a few degrees may have a negative impact on the outcome. Performing the split in situ also has other advantages. Significantly less bleeding occurs when the organs are reperfused. The two liver grafts can be assessed in the donor immediately
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FIGURE 53-3 n The line of transection on the hepatic parenchyma is just to the right of the middle hepatic vein.
FIGURE 53-4 n The completed split in situ, which allows one to examine the two lobes to ensure that there are no areas of devascularization and also helps to minimize cold ischemia time.
after parenchymal transection and before vascular interruption, to ensure no significant ischemia at the borders of the cut edge of the liver (Fig. 53-4). Previous SLT series have shown superior results with in situ versus ex situ liver splits.7,8 For all these reasons we feel that the actual splitting of the donor liver should be performed in situ. Disadvantages of the in situ procedure include the time added to the procurement during the parenchymal transection and the potential for hemodynamic instability in the donor if there is any significant bleeding. This can affect not only the liver itself but also the other organs that are being removed during the procurement. Once the transection is complete, the liver and other abdominal organs are flushed with cold preservative solution as usual and the liver is removed. On the back table the previously isolated vasculature to the right lobe is divided to completely separate the two grafts. Any important hepatic venous tributaries from the right lobe draining into the middle hepatic vein (segment V or VIII) that had been divided during the parenchymal
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FIGURE 53-5 n The split is completed on the back table by final division of the vascular structures. Important middle hepatic vein tributaries of the right lobe can be reconstructed using conduit from the donor.
HA HA CBD
A
PV
Roux limb
B
PV
FIGURE 53-6 n The right lobe (A) and left lobe (B) can then be implanted in the respective recipients. The left lobe is done in a piggyback fashion. The right lobe can be either caval replacement (as shown) or piggyback. CBD, Common bile duct; HA, hepatic artery; PV, portal vein.
transection can now be reconstructed. This can be done by using vascular conduit from the deceased donor and anastomosing the cut surface veins to the preserved donor IVC using vascular conduit (such as iliac vein) from the deceased donor (Fig. 53-5). The preceding description is our preferred technique, but several variations have been described. Two important ones include the cava splitting method and the middle hepatic vein splitting technique. In the cava splitting method the left lobe is not mobilized from the IVC. Rather the cava is split down the middle on the back table, thus preserving a portion of it as a patch with both the right and left lobes.9 This technique has the advantage of preserving all of the outflow of the left lobe, including the short hepatic veins. The middle hepatic vein splitting technique involves ex situ transection of the hepatic parenchyma with division of the middle hepatic vein longitudinally along its length. This can then be reconstructed in both the right and left lobe grafts using a vein patch, hence preserving the middle
hepatic vein with both lobes and maximizing outflow for both grafts.10
Recipient (Figure 53-6) Right Lobe Graft The deceased donor SLT right lobe graft is implanted in a manner similar to that used for a right lobe living donor graft. The diseased liver in the recipient is removed, and the IVC can be either preserved or removed. If the IVC has been preserved with the right lobe graft, either a caval replacement, piggyback, or side-to-side cavaplasty technique can be used for outflow reconstruction. Ensuring adequate outflow of the right graft is crucial. The donor right portal vein is then sewn to the recipient right or common portal vein (depending on which is the better size match). The donor right hepatic artery is sewn to the recipient right hepatic artery. Biliary reconstruction is then
53 Split Liver Transplantation for Two Adult Recipients
performed either with a duct-to-duct technique or with a Roux-en-Y hepaticojejunostomy. Left Lobe Graft The left lobe is implanted in a standard piggyback fashion with preservation of the recipient’s IVC. The donor hepatic veins can be anastomosed to the recipient’s left and middle hepatic vein confluence with good size match. The remainder of the vascular connections are done in a standard fashion.
RESULTS The initial series of adult/pediatric SLT until the mid1990s demonstrated poor recipient and graft survival of 50%.11,12 However, by the mid-1990s reports from the European Split Liver Registry showed 6-month patient and graft survival similar to whole-liver transplant.13 Single-center North American series, as well as analyses of registry data, similarly demonstrated improving outcomes with SLT for adult/pediatric recipients. Data on outcomes for SLT for two adults is significantly less robust, with mostly small single-center series or case reports in the literature, highlighting the infrequency of these procedures. No registry reports for SLT for two adult recipients have been reported. The American Society of Transplant Surgeons (ASTS) survey performed between April 2000 and May 2001 elicited a response from 83 of 89 surgical teams identified from the annual report of the Scientific Registry of Transplant Recipients as having performed at least one SLT procedure during the previous year. Thirty-six of the responding teams reported data on 207 left lateral segment, 152 right trisegment, and only 15 left lobe, and 13 right lobe grafts.14 Therefore left and right lobe graft data from the ASTS survey do not permit meaningful analysis. Nonetheless, the reported overall incidence of left lobe complications was 26% versus 22% for right lobe grafts, with the majority used for urgent recipients. Biliary complications were most frequent, with vascular complications reported in 4% of left lobe versus 9% of right lobe grafts. Primary nonfunction and graft failure were 7% and 9% for left lobe versus 9% and 14% for right lobe grafts, respectively. Recipient death was observed in 7% of left versus 8% of right lobe grafts. Single-center reports from Europe, North America, and Asia, even though each is relatively small in size, have provided more meaningful data on outcomes after these procedures. Azoulay et al15 reported their outcomes of transplantation with right and left split-liver grafts and also compared with those of whole-liver transplants. For whole-liver, right and left split-liver grafts, respectively, patient survival rates were 88%, 74%, and 88% at 1 year and 85%, 74%, and 64% at 2 years. Graft survival rates were 88%, 74%, and 75% at 1 year and 85%, 74%, and 43% at 2 years. Patient survival was adversely affected by graft steatosis and recipient’s inpatient status before transplantation. Graft survival was adversely affected by steatosis and a GWBWR of less than 1%. Primary nonfunction occurred in three left split-liver grafts. The rates of arterial (6%) and biliary (22%) complications were
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similar to published data from conventional transplantation for an adult and a child. SLT for two adults increased the number of recipients compared with whole-liver transplantation and was logistically possible in 16 of the 104 (15%) optimal cadaver donors. Humar et al16 reported their experience of in situ splitting of livers from six cadaver donors and transplanted into 12 adult recipients at the University of Minnesota. The patient and graft survival were 80% each, and arterial and biliary complications occurred in 16% and 25% of recipients, respectively. Analysis of the split-liver transplantation data suggested a time-dependent learning curve, which was applicable to surgical splitting technique, implantation, and recipient selection. Not all single-center reports have been positive, with some reporting a high incidence of complications and graft loss. One center in Italy recently reported on 16 adult patients who underwent SLT using 9 full right lobe grafts (segments V to VIII) and 7 full left lobe grafts (segments I to IV).17 The splitting procedure was always carried out in situ with a fully perfused liver. Postoperative complications were recorded in 8 (50%) patients: 5 right lobe recipients and 3 left lobe recipients. No one was retransplanted. After a median follow-up of 55.82 months (range, 0.4 to 91.2), 5 (31%) patients died, and the 1-, 3-, and 5-year overall survival rate for patients and grafts was 69%, leading the authors to question whether SLT for two adult recipients should even be performed. However, other single-center reports from the same area have had more positive results. Cescon et al18 reported on 22 adult patients receiving SLT and demonstrated good results. Overall patient and graft survival were 90% and 86%. Patient survival was 84% in recipients of right grafts and 100% in recipients of left grafts. Graft survival was 84% and 89%, respectively.
COMPLICATIONS Complications after SLT are generally similar to those that may occur after any type of transplant, though the overall incidence of certain types of complications may differ. In addition, there are some conditions unique to partial lobe transplants and generally not seen with whole-liver transplants that can contribute to complications. An example of this is the cut surface of the liver present on both the left and right lobe grafts, which may be an additional source of complications such as bleeding or bile leak. Overall, given the technically demanding nature of the procedure and the partial nature of the graft, surgical complications tend to be more common after SLT compared to whole-liver transplants, though published reports suggest it is similar to the reported incidence of complications after live donor transplants.
Vascular Complications The incidence of vascular complications after whole-liver transplantation is 5% to 10% and is likely to be at least twice that in SLT recipients. Thrombosis is the most common early event; stenosis, dissection, and pseudoaneurysm formation are less common. Any of the vascular
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anastomoses (hepatic artery, portal vein, and hepatic vein) may be involved, but the hepatic artery is most common. Hepatic artery thrombosis has a reported incidence of 5% to 10%, higher than reported in whole-liver transplantation, likely because of the smaller caliber of vessels and the sometimes complex arterial reconstruction required. Thrombosis of the portal vein is less frequent (compared with the hepatic artery) but again is likely more common than in whole-organ recipients. Complications of the hepatic veins (such as thrombosis and stenosis) are uncommon but again have a higher incidence in the partial grafts. The risk for problems may be higher in recipients of the left lobe graft because the segment may be quite mobile, and if it is not properly aligned, it may twist on the anastomosis, obstructing flow. Presentation is usually with massive ascites and graft dysfunction. Ultrasound Doppler examination will usually demonstrate this, as well as the other early vascular problems, and some form of routine monitoring is warranted to aid in early diagnosis.
Biliary Complications Complications of the biliary system continue to be the most common type of surgical complication after SLT. The incidence is 20% to 40% with an associated mortality of less than 5%. Biliary complications manifest as either a leak or an obstruction. Timing often determines type and clinical outcome of the complication. Bile leaks tend to occur early postoperatively and often require surgical repair, whereas obstruction usually occurs later and can often be managed with radiological or endoscopic techniques. Most bile leaks occur within the first 30 days after transplantation and can be from the anastomotic site or the cut surface of the liver. The area around the anastomosis has the most tenuous blood supply: both the donor common bile duct (CBD) and the recipient portion of the CBD are supplied by end arteries. Excessive dissection or cauterization around the donor or recipient CBD can further disrupt the blood supply, leading to ischemic complications. Another important cause of biliary tract complications is hepatic artery thrombosis: the donor CBD receives its blood supply from the hepatic artery. With any biliary tract complication the hepatic artery should be carefully assessed to document patency. Other causes of leaks include poorly placed sutures, excessive number of sutures, and tension on the anastomosis. With partial transplants the cut surface of the liver represents an important site for a bile leak. Careful parenchymal transection can help to lower the incidence. The in situ technique of liver transection can also help to minimize the risk for cut surface bile leaks. Biliary obstruction is usually secondary to stricture and occurs later in the postoperative period. It is most common at the anastomotic site and is likely related to local ischemia. Nonanastomotic strictures usually have a worse prognosis; they are associated with hepatic artery thrombosis or prolonged cold ischemic times. The treatment is usually not operative, but rather by percutaneous or endoscopic interventions. If these initial options fail, surgical revision is required.
Small-for-Size Syndrome Small-for-size syndrome (SFSS) has emerged as an interesting and significant problem that is fairly unique to partial liver transplants. SFSS and injury related to the use of small-for-size grafts were reported initially by Emond et al.19 Although there is no uniform consensus on the definition of SFSS, the diagnosis is generally based on persistent hyperbilirubinemia and massive ascites during the posttransplant subacute phase without evidence of any other cause. The incidence is reportedly close to 10%, though the exact incidence is unknown because the definition of this condition is not agreed upon. Multiple risk factors have been identified, including the size of the graft, the type of graft, the degree of portal hypertension, and the spleen size. Of these, the degree of portal hypertension and portal perfusion is likely most important. The pathophysiological characteristics of the condition are believed to be related to damage to hepatocytes and vasculature secondary to portal shear stress. Portal hyperperfusion leads to poor hepatic arterial inflow because of the arterial buffer response, which ultimately leads to hepatic necrosis and poor hepatic regeneration.20 In the absence of any intervention, SFSS is associated with a significant mortality early after transplant, with many of the patients succumbing to complications associated with poor graft function, such as infections and multiorgan failure. With increased understanding of the concept of small for size, strategies to prevent SFSS and strategies to rescue small-for-size grafts are being developed (Table 53-1).
UNANSWERED QUESTIONS Ethics of Splitting Surgical complications are more common in SLT (versus whole graft) recipients, related to the cut surface of TABLE 53-1 M echanisms and Possible Methods of Avoiding or Treating Small-for-Size Syndrome Mechanism of Small for Size Prevention strategies
Suboptimal graft quality Insufficient graft volume Impaired venous outflow
Treatment strategies
Increased portal flow or pressure
Strategies Younger donor, nonfatty liver, decreased ischemia time Adequate graft volume (GWBWR ideally should be ≥0.8%) Wide venous anastomosis, reconstruction of segmental drainage Portosystemic shunt, splenectomy, splenic artery ligation, medical therapies (e.g., octreotide)
GWBWR, Graft weight–to–body weight ratio.
53 Split Liver Transplantation for Two Adult Recipients
the liver, smaller vessels for anastomosis, and more complicated biliary reconstruction. Therefore one important aspect of the recipient selection process is adequately informing the potential recipient of the splitting procedure and obtaining informed consent. Who makes the decision of whether a liver should be split at the present time? The question of how much role the recipient plays in the decision to split the liver is unclear.
Allocation How best to allocate a liver for splitting is completely undecided at the present time and varies from country to country and from region to region. Should the liver from an ideal donor be preferentially allocated for a split procedure, and if so, how does this affect the sickest patients at the top of a waiting list who may be too sick for a partial liver transplant? Not all centers may have the technical expertise or personnel to perform splits—should ideal livers be preferentially allocated to centers that have such expertise and personnel available?
Split Potential More data are needed to better define donor and recipient selection criteria, which are crucial to success. It is difficult to estimate how much impact adult SLT will have on the donor pool. About 25% of all deceased donors in the United States are between 15 and 35 years of age. If even half of these livers could be used for splits, the number of liver transplants could potentially increase by 10%, or by close to 500. With better preservation techniques, more livers may be amenable to splitting. In the near future this technique will likely become part of every major liver transplant center's repertoire in order to provide the maximum advantage for their candidates on the waiting list.
SUMMARY Given proper donor and recipient selection, SLT can be successfully applied for two adult recipients. Donors should be “ideal,” (i.e., young, large, and hemodynamically stable with normal liver function test results). Careful evaluation of the donor hepatic artery and biliary anatomy intraoperatively is essential to helping decide if the split is technically possible. The split itself may be performed ex situ or in situ, but the latter method helps to minimize graft ischemia. Recipients should not be critically ill; careful attention should be paid to the size, especially for left lobe graft recipients. Further experience will help to better define the limits of this procedure and improve results. At present this represents a technique that can help to expand the donor pool in a limited number of circumstances, but there is a potential for growth.
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Pearls and Pitfalls • Paramount to the success of split-liver transplantation is proper donor and recipient selection. • Split procedures can be performed in situ or ex situ; the in situ technique reduces cold ischemia, enhances identification of biliary and vascular structures, and reduces hemorrhage upon graft reperfusion. • Cold ischemia time can have a significant impact on the outcomes, and every effort should be made to minimize cold ischemia time, especially in the left lobe graft recipient. • The right lobe of the split usually has more outflow issues, whereas the left lobe has more size issues. • Meticulous attention to technical detail is crucial for ensuring successful outcomes in this technically challenging procedure.
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PART VI Split and Living Donor Transplantation
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