Living Donor Hepatectomy

The history of liver surgery stretches back to ancient times, when battle surgeons introduced debridement of damaged liver segments from open wounds. However, formal entry into the abdominal cavity to treat a liver tumor or to drain an abscess began with the advent of general anesthesia and antisepsis in the late 1800s.

With a better understanding of hepatic anatomy and the segmental structure of the liver, surgeons started performing partial liver resections. The first successful resection of a liver tumor was performed in 1887 in Germany by Langenbuch, the same surgeon who performed the first successful cholecystectomy 5 years earlier.

The lessons learned during World War II concerning liver trauma, blood supply to the liver, and bleeding control spurred the confidence of liver surgeons and marked the beginning of the modern era of liver operations. ^[1] Two landmarks of paramount importance have marked this period. The first was Cuinaud’s detailed description of the segmental anatomy of the liver based on blood supply (see image below). ^[2] The second, and probably brightest landmark of this period, was the first whole-liver transplantation by Thomas Starzl in 1963. ^[3]

As experience with liver resections increased dramatically while the supply of cadaveric liver grafts became increasingly inadequate to meet the needs for liver transplants, the concept of resecting a healthy person’s liver to use for support of another person’s life was raised.

The concept of living donor liver transplantation (LDLT) emerged originally for pediatric patients because of the high mortality rate among children awaiting a cadaveric graft ^[4] and the fact that a child needs only a small allograft, so an adult donor would not need to undergo major hepatectomy. ^[5]

Raia et al from Brazil described the first attempt of LDLT a child, in 1989. ^[6] Although the recipient did not survive, other centers followed, and the first successful pediatric LDLT, from a mother to her son, was performed by Strong in Australia that same year. ^[7]

In the United States, the first successful LDLT from a parent to a child was performed the same year at the University of Chicago. ^[8] Before this first procedure, the physicians involved published a manuscript describing the protocol for donor and recipient selection, risks and benefits, and the use of the donor advocacy panel. ^[9] A few years later, reports first showed that the introduction of LDLT dramatically decreased the mortality of children on the waiting list. ^[10]

With the success of the LDLT in the pediatric population, transplant centers started to embrace the idea of using LDLT in adult recipients. The first successful cases were reported in Japan, where cadaveric grafts are extremely scarce owing to cultural constrains to organ donation. ^[11]  Japanese transplant teams reported excellent results with the use of left- and right-lobe grafts. ^[12]

The initial results from the LDLT experience in the United States were not as encouraging, ^[13] so the first decade of adult-to-adult LDLT developed very slowly, with only 34 such procedures performed between 1991 and 1998. ^[8] Many of the failures resulted from the underappreciated importance of donor graft size to recipient size. In the pediatric population, this issue was absent, since the size of the recipient was always much smaller than that of the donor. In adult patients, the graft was often too small, the posttransplant function was poor, and, in some cases, there was primary nonfunction. ^{[14, 15]}

After surgeons realized this concept and avoided smaller grafts for larger recipients, the success of adult-to-adult LDLT increased, along with the number of such transplantations performed. Thus, from 1988-2021, 8370 LDLT were performed in the United States. ^[16] Enthusiasm for adult-to-adult LDLT in the United States peaked in 2000, with 49 centers performing this operation. However, the enthusiasm fell sharply after a donor death in 2001, which changed the climate for living donation. ^[17]  

The donor death resulted in numerous position papers, conferences, and review boards. ^[18] New York State created a review committee and document that mandated guidelines for transplant centers and physicians performing LDLT. ^{[19, 20]} Additionally, the National Institutes of Health (NIH) sponsored a multicenter prospective study of adult-to-adult LDLT, which includes 9 centers in the United States. The Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL) has published outcomes and suggestions concerning LDLT in adult patients, ^{[21, 22]}

From 2001-2006, the number of centers performing adult LDLT decreased, and the number of operations performed declined and then stabilized at around 250 cases per year, or 5% of the total number of liver transplantations in adults, approximately half of the peak in 2001. ^[19]  However, since 2015, these numbers have been steadily, increasing reaching a record 563 LDLT performed in 2021. ^[16]

To be considered eligible for LDLT, a patient should be able to fulfill the minimal listing criteria for deceased donor (DD) transplantation. All potential LDLT recipients must first be listed on the regular liver transplant waiting list with the United Network for Organ Sharing (UNOS). ^[23] Any contraindication for DD transplant applies to living donor recipients, which is why, in all centers, the evaluation of a potential donor does not start until the recipient is listed.

In the pediatric population, eligibility for LDLT comes with the listing of the patient for DD transplant. Because procurement surgery for a pediatric LDLT is associated with fewer complications than that for an adult recipient and outcomes in the pediatric population are generally better, ethical issues to determine the eligibility of the recipient are uncommon. ^[24]

However, in the adult population, such issues play an important role in determining eligibility for LDLT. ^[25] Because living donation involves a healthy individual placed at surgical risk for the benefit of a transplant recipient, the general concept is that LDLT should be performed in recipients who would not receive a DD transplant as soon as they need it, based on the severity of their illness. In other words, the shortage of DD organs is the paramount principle of living donation. However, for this to be ethically justified, the anticipated survival of the recipient should be sufficient to support such an act.

To justify the risk to the donor, the outcome after LDLT should at least equal the outcome after deceased donor liver transplantation (DDLT) and the ability to decrease death among potential recipients on the waiting list. LDLT graft survival  average 87% at 90 days and 81% at 1 year, and improve as the center volume increases. ^[26]

Just as important as posttransplant survival rate is the effect of LDLT on the risk of death among those on the waitlist. In a 2007 report, LDLT was associated with a lower mortality rate than the alternative of waiting for a DDLT, with an adjusted mortality hazard ratio of 0.56 for LDLT. ^[21]

Posttransplant outcomes depend partly on the severity of the recipient’s disease. With the implementation of the model for end-stage liver disease (MELD) system for allocation of liver allografts, the sickest patients are prioritized for transplantation (see the MELD Score calculator). ^[27] The postoperative mortality rate after liver transplantation is higher in patients with a high MELD score, regardless of whether DDLT or LDLT is performed, with higher mortality rates with the latter than the former. ^[28]

The explanation of the increased mortality rates following LDLT among sicker patients is that a partial graft is unable to meet the needs of a patient experiencing severe and prolonged illness. Therefore, many transplantation centers and the New York State of Health Department have recommended that LDLT should not be offered to patients with a MELD score above 25. ^[29]  With the application of that principle, the 1-year patient survival for LDLT has improved to 86%. ^{[30, 31]}

Ideal candidates for living donor liver transplantation

Two groups of recipients are considered ideal candidates for LDLT.

The first group includes patients with hepatocellular carcinoma confined to the liver and without liver decompensation. ^[32] These patients are not sick enough to be placed high on the list based on their MELD score, but their cancer may soon render them unsuitable for transplantation if they develop extrahepatic disease. Data from Japan demonstrate that LDLT for hepatocellular carcinoma yields results that are comparable to LDLT performed in patients without hepatocellular carcinoma. ^[33]

The second group includes patients whose MELD score does not reflect the severity of their illness. These are patients with complicated cholestatic liver disease, severe encephalopathy, ascites, or cachexia whose illness is much worse than suggested by their MELD score. They are very low on the priority list, and their likelihood of receiving a DDLT is very low, while their risk of death while on the waiting list is very high. ^[34]

The selection of the donor has ethical and medical considerations.

Ethical considerations center on the 3 healthcare ethics principles ^[35] :

• Autonomy,
• Beneficence/nonmaleficence
• Justice

Autonomy for the donor involves the respect for his or her right to act intentionally and without coercion. The donor has the right to choose what may be a high-risk donation, provided that consent is fully informed. The principle of informed consent goes beyond explanation of the surgical procedure. All the information about the risks and benefits of the living donation, as well as all national and center data, should be included in the consent discussion.

The principles of beneficence (doing good) and nonmaleficence (not inflicting harm) are, at times, in competition in the cases of living organ donations, since healthy individuals are undergoing a potentially harmful procedure to help someone else.

Justice weighs the fairness of treatments for individuals and the larger society. ^[8]

Donor advocacy panels are an integral part of all centers that perform LDLT. Their main task is to ensure that all the above principles are strongly present and are followed in the evaluation of every donor.

Medical considerations of the living donor are that (1) the donor must be in excellent health in order to be able to undergo the operation and the postoperative and recovery period with minimal physical and psychological distress and that (2) the liver of the donor is of such quality and size that it can be divided in a way that can support both the donor and recipient. These are two separate issues for which testing criteria often overlap but that are at times in conflict. In such cases, donor safety is the priority.

In brief, most potential donors are excluded based on initial studies to rule out underlying conditions that represent increased surgical risk, such as hypertension; diabetes; and hepatic, cardiac, renal, and pulmonary problems. In addition, donors who are younger than 18 years or older than 55 years, as well as pregnant women, are excluded. ^[36] Chronic infections, especially hepatitis and HIV, are traditionally exclusion criteria in most centers. Hypercoagulable states are relative contraindications depending on the severity of the disorder, given the risk of increased donor mortality due to embolic episodes and increased recipient mortality due to portal vein thrombosis. ^[37]

The potential donor liver is evaluated thoroughly with laboratory and radiology tests. Liver function test results should be perfect in order to proceed to the radiologic evaluation of the liver. High-resolution CT scanning with angiography and cholangiography or MRI are the most common modalities used in most centers. ^[38] The examination of liver quality is very important. Relevant steatosis must be excluded, as it lowers the functional liver mass. Any other parenchymal abnormalities (eg, iron deposits, tumors) should also be ruled out.

Liver volumetry is paramount. Modern CT (eg, MeVis Liver Analyzer and LiverView) and MRI software produce virtual 3-dimensional liver models that enable volume measurements (total liver and graft volumes) and permit virtual hepatectomy as part of presurgical planning. Accurate size matching of the donor and recipient is essential to ensure that functional hepatic mass is available both to sustain metabolic demands and to permit volume regeneration. Inadequate liver volume in the donor will lead to liver failure; inadequate liver volume in the recipient will lead to small-for-size syndrome (SFSS) and primary nonfunction. ^[39] The critical threshold of the remnant liver volume in most centers is 35%, although many centers use 40%; the lowest limit has reported to be 27%. ^[40]

SFSS in adult-to-adult LDLT remains the greatest limiting factor for the expansion of segmental liver transplantation. SFSS develops in the first 1-2 weeks after transplantation and is characterized by prolonged cholestasis with elevated serum bilirubin levels, coagulopathy, elevated liver enzyme levels, ascites, and, in severe cases, gastrointestinal bleeding and primary nonfunction with encephalopathy, acidosis, renal failure, and shock. ^{[41, 42]}

Portal hyperperfusion, venous pathology, and the arterial buffer response are considered the main contributors to the clinical and histological manifestations of the syndrome. ^[43] Data have suggested that the exposure of a small graft to persisting hyperdynamic circulation and high portal blood inflow results in sinusoidal congestion and hemorrhage, inducing impairment of liver regeneration and hepatic dysfunction. ^{[44, 42]}  

Furthermore, the high portal blood inflow causes a compensatory decrease in arterial blood flow. This phenomenon, known as the buffering response, results from a reciprocal compensatory regulation between portal vein and hepatic artery inflow and might contribute to worsening of the graft injury. ^[45]

Earlier data suggested that a graft-to-recipient weight ratio (GRWR) of less than 0.8% or a graft liver volume of less than 30% of standard estimated volume is a risk factor for the development of SFSS. Most centers do not accept grafts smaller than that, especially when the recipient has portal hypertension. ^[46]

Finally, a comprehensive vascular and biliary roadmap facilitates detailed surgical planning and reduces postoperative complications in both donor and recipient. ^[47] All the potential anatomical variations should be clearly demonstrated and identified, as this will provide the surgeon with the ability to plan the surgical technique and to identify grafts that would be inappropriate because of anatomical variations.

Contraindications to LDLT in the donor include the following:

• Age younger than 18 years or older than 55 years
• Any type of liver disease
• Anatomical contraindications such as insufficient liver volume or vascular and/or biliary variations that preclude a safe liver resection
• Obesity with body mass index (BMI) greater than 35 kg/m ²
• Any type of severe comorbidities such as coronary artery disease, cerebrovascular disease, severe uncontrolled diabetes, or hypertension
• Psychosocial problems that may compromise an uneventful recovery and restoration of physical and social function

Contraindications to LDLT in the recipient include the following:

• All contraindications for liver transplantation (eg, active infection, active extrahepatic malignancy)
• Severely decompensated liver failure (MELD score >25 in most cases is a contraindication to LDLT)
• Cholangiocarcinoma
• Previous graft failure due to recurrent hepatitis C
• Acute alcoholic hepatitis
• Need for combined liver-kidney transplantation

Early postoperative complications may include the following:

• Liver failure
• Vascular problems (eg, portal vein thrombosis) ^[48]
• Intra-abdominal bleeding
• Bile leak
• Wound infection/dehiscence
• Pulmonary complications (pneumonia, embolus)
• Pain
• Other (eg, phlebitis, brachial plexus injury)

Late postoperative complications may include the following:

• Chronic pain
• Psychological impact of poor recipient outcome
• Late bile duct strictures
• Other (eg, adhesions and associated intestinal obstruction)