Split Liver Transplantation 

The need for liver transplants currently far eclipses the supply of available donor organs. According to 2005 statistics from the United Network for Organ Sharing (UNOS), the waiting list for a liver transplant now exceeds 17,000 patients.^[1] Despite considerable efforts to increase the supply of available deceased donor organs, the number of deceased donor liver transplants has been fairly constant at 5000 livers per year. As a result, many patients continue to die while awaiting a life-saving transplant.

The shortage of available organs was previously most acute for pediatric patients. Because of the small number of pediatric donors, the mortality rate among patients on the wait list was commonly high when only whole-organ transplantation was performed.^[2] In 1984, the introduction of reduced-liver transplant in which a portion of the adult liver was given to infants and children dramatically reduced this mortality rate. Over the past 20 years, the risk of death among patients on the pediatric weight list has substantially declined because of the ability to use these reduced-size grafts and because of the subsequent introduction of live-donor transplantation.

As most commonly performed, split-liver transplantation (SLT) involves the division of donor liver from a deceased adult between a pediatric recipient and an adult recipient to maximize the benefit of each available donor organ.

For excellent patient education resources, visit eMedicine's Liver, Gallbladder, and Pancreas Center and Hepatitis Center. Also, see eMedicine's patient education articles, Cirrhosis and Liver Transplant.

Given the high wait-list mortality rate among pediatric patients with end-stage liver disease and our improved understanding of segmental liver anatomy, various techniques were developed to provide reduced-size allografts with complete arterial, portal, biliary, and venous drainage. Although split-liver transplantation was initially used for the pediatric population receiving deceased-donor grafts, the lessons learned from split-liver transplantation have been successfully applied to live-donor liver transplantation to benefit pediatric and adult recipients.^[3]

In 1984, Bismuth and Houssin reported successful transplantation of a reduced-size liver in which only a portion of the donor organ was used and the remaining liver discarded.^[4] In reduced-size liver transplantation, the liver allograft can be tailored to the recipient's size by using various functional lobes or segments. The graft most commonly used in pediatric patients includes the left lateral segments (segments 2 and 3) and the left lobe (segments 2-4). The right lobe (segments 4-8) is rarely used in pediatric patients because it does not offer notable size advantages over whole livers. Although this technique was successful in increasing the number of pediatric transplants, it did not increase the total number of organs available for transplantation.

In 1990, Strong et al reported the first successful living-related liver transplantation for pediatric recipients utilizing the left lateral segment from a mother to her son.^[5] Broelsch and colleagues (1991) subsequently reported outcomes in 20 children receiving left lateral segments from adult living donors. Patient survival was 85%.^[6]

Since these initial experiences, live-donor transplantation has been expanded to adult recipients and is currently the subject of a large multicenter trial by the National Institutes of Health (NIH), ie, the Adult To Adult Living Donor Liver Donor Liver Transplantation Cohort Study (A2ALL). Advantages of living-donor liver transplantation include the selection of an ideal donor, the ability to schedule the case electively, the maximal time to prepare the recipient, and the relatively short cold ischemia time. Although living-donor transplantation increases the number of livers available for pediatric and adult recipients, donor safety remains a major concern. Several donor deaths were highly publicized. Although the exact risks remain uncertain, serious donor morbidity and mortality are possible. Ethical issues, such as those regarding donor coercion and informed consent, raise concerns about application of this technique in both urgent and elective settings.

Split-liver transplantation takes advantage of the knowledge gained in reduced-liver transplantation to increase the organ supply by using the right lobe or trisegmental graft that remains after the left lateral segment or left lobe is removed for a pediatric recipient. In 1998, Pichlmayr et al described the technical approach to split-liver transplantation, including preservation of arterial, biliary, venous drainage for both grafts.^[7] Broelsch reported the first large series in 1990,^[8] although the results were initially poor, hampering widespread acceptance of this technique.^{[9, 10, 2]} Early series had higher-than-expected rates of primary nonfunction and biliary complications that substantially reduced recipient survival. Ethical questions were also raised about the potential of disadvantaging adult recipients to provide grafts for pediatric patients.

In the past 10 years, refinements in surgical techniques and improved organ preservation have improved patient survival rates. Particularly in the case of right trisegment–left lateral segment splits, adult recipients can expect results that approach those of patients who receive transplants from standard deceased donors.^{[11, 12, 13, 14, 15, 16]} The success of split-liver transplantation in children has led some authors to argue that live-donor transplantation is no longer necessary in the pediatric population.^[17] Overall, the transplantation community has endorsed the expanded use of split-liver transplantation as a technique to increase the organ supply and to reduce wait-list mortality rates.^[18]

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

For pediatric patients, biliary atresia remains the most common indication for liver transplantation, followed by fulminant hepatic failure, metabolic diseases, and various other causes, including cholestatic diseases and malignancy (hepatoblastoma). Given the preponderance of childhood transplantation for biliary atresia, a considerable number of children undergoing transplantation are younger than 2 years and, therefore, excellent candidates for a left lateral segment graft from a split liver. Older children require larger grafts, including left-lobe grafts, which have increased rates of graft loss and complications, although the increase may reflect differences in recipients' characteristics and their underlying illnesses.^[19]

The etiologies of liver disease in adult recipients of split-liver transplantations do not notably differ from those receiving whole-organ grafts. Initial concerns regarding the potential for increased recurrence of hepatitis C in regenerating allografts have not been validated in the literature.^[20] Split-liver transplantation has now been applied in all patient groups, including status 1 patients and patients requiring retransplantation.^[16]

Frequency

In the young pediatric population, split-liver transplantation or reduced-liver transplantation has become an increasingly frequent procedure. In a recent review of 755 patients undergoing transplantation for biliary atresia, only 44% received whole-organ grafts. Deceased-donor variants (reduced or split) represented 31% of grafts, whereas live donors provided the remaining 24%.^[21]

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

Split-liver transplantation (SLT) has traditionally been restricted to ideal deceased donors. Although the exact definition of ideal donors remains controversial, the following characteristics are used to exclude donors from consideration according to the Organ Procurement and Transplantation Pediatric Subcommittee:

• Age younger than 10 years or older than 40 years
• History of cancer or insulin-dependent diabetes mellitus
• Infection with HIV, hepatitis B virus, or hepatitis C virus
• Use of both dopamine and dobutamine
• Serum bilirubin value of more than 3 mg/dL
• Serum alanine aminotransferase (ALT) or serum aspartate aminotransferase (AST) level greater than 150 U/L
• Cardiac arrest after neurologic event leading to brain death
• Serum sodium level of more than 170 mEq/L

In a 2000 study from the University of California at Los Angeles (UCLA) in 110 patients, the length of donor hospital stay, the donor's sodium level, and prolonged warm ischemia were donor- and procedure-dependent risk factors for poor outcome after split-liver transplantation.^[22] In addition, a suitable pediatric recipient must be available for the left lateral segment or left lobe.

The goal of split-liver transplantation (SLT) is to produce 2 grafts with preserved vascular supply (ie, portal vein, hepatic artery), venous drainage, and bile duct. Anatomic variations (replaced arteries, biliary anomalies) are not considered to be a contraindication to liver splitting as long as both right- and left-sided allografts have a complete set of vessels and biliary drainage. In most cases, the vena cava and the common bile duct are maintained with the right-sided allograft, and the left hepatic vein and left bile duct are divided for the left allograft.

For left-lobe grafts, the middle and left hepatic veins are preserved. In these cases, the surgeon transplanting the right-lobe graft should recognize and either preserve or reconstruct the large veins in segment 5, which frequently drain in the middle hepatic vein. The main portal vein and the main arterial supply can be maintained with either side depending on the anatomy and who was designated the primary recipient of the allograft.

Hemodynamically instability of the donor is a contraindicated for split-liver transplantation (SLT). Donors staying in the hospital for longer than 5 days and those with liver function results exceeding 3 times the mean should not be considered for splitting. Anatomically aberrant hepatic arterial anatomy is not a contraindication to splitting as long as the arterial supply to each of the segmental grafts is not compromised.