Living donor liver transplant: A strategy to increase transplant access.

Living donor liver transplant (LDLT) developed as an innovative response to the scarcity of deceased donor grafts. Adult right lobe LDLT, pioneered in Hong Kong in 1996, was a seminal advancement in liver transplantation, introducing a viable alternative to the established deceased donor liver transplant (DDLT) paradigm. Adult LDLT (ALDLT) grew in the US to a peak of 9% of the total adult liver transplants but stalled following several highly publicized donor deaths (Figure 1). The Adult-to-Adult Living Donor Transplantation Cohort Study (A2ALL), a 14-year retrospective and prospective cohort of 1136 LDLT and 464 DDLT recipients and donors, was pivotal in demonstrating the safety and efficacy of LDLT for donors and recipients.1 One of the studies from the Adult-to-Adult Living Donor Transplantation Cohort Study cohort was the first to demonstrate a survival benefit when comparing patients who underwent LDLT against those who remained on the waitlist or received DDLT (adjust mortality HR 0.56; p < 0.001) largely secondary to lower MELD at transplant and shorter waiting time.2 The survival benefit associated with LDLT extends to MELD as low as 11, with a 34% decrease in mortality when compared with the waiting list.3 This contrasts with DDLT, where the risk of transplant outweighs the survival benefit of transplant until MELD is over 15.4FIGURE 1: Liver transplants by donor type from 1988 to 2021. Data obtained from the Organ Procurement Transplantation Network.WHAT ARE THE MANAGEMENT DIFFERENCES BETWEEN DECEASED DONOR AND LIVING DONOR LIVER TRANSPLANT? The main differences in the management of LDLT and DDLT are the pretransplant evaluation and surgical management. The pretransplant evaluation for LDLT is key to ensuring a successful transplant and takes on a heightened sense of gravity, given the potential risk to the donor. The Organ Procurement and Transplantation Network established requirements for LDLT donor evaluation, including the assessment of past medical and surgical history, biochemical testing and imaging (Table 1), evaluation by an independent donor advocate, informed consent, and an anatomical assessment of the vasculature and biliary tree.5 The overall acceptance rate of donors is 40%, with major donor-related reasons for denial being medical contraindications, psychosocial considerations, steatosis greater than 10%–15%, and anatomical contraindications.6 A thorough radiological assessment is required to ensure a graft-to-recipient weight ratio (GRWR) of ≥0.8, graft weight of 40% of the standard liver mass, donor remnant volume of >35%, and no vascular or biliary abnormalities. Adequate GRWR is a critical factor to avoid allograft dysfunction and must be considered in the context of graft quality, donor age, and MELD of the recipient.7 TABLE 1 - Donor evaluation testing. Biochemical testing Imaging and ancillary testing ABO CT angiography or MRI abdomen for assessment of steatosis and vasculature of the donor CBC Liver biopsya CMP Electrocardiogram PT/PTT Echocardiogram Viral labs (HBV, HCV, HIV, CMV, EBV, Rubeola) Chest x-ray RPR Cardiac stress testa Chronic liver disease workup (Ceruloplasmin, A1AT, autoimmune serologies) Heart catheterizationa Hypercoagulable panel Pulmonary function testa aOnly if clinically indicated.A1AT indicates alpha-1 antitrypsin; ABO, ABO blood group; CBC, complete blood count; CMP, comprehensive metabolic panel; CMV, cytomegalovirus; EBV, Epstein-Barr virus; PT, prothrombin time; PTT, partial thromboplastin time; RPR, rapid plasma regain. While the surgical management of DDLT is relatively standardized, right lobe LDLT is often technically challenging due to complicated biliary and hepatic vein reconstructions. Biliary reconstruction can be performed through hepaticojejunostomy or duct-to-duct anastomosis. The duct-to-duct anastomosis can be challenging in right lobe LDLT, as nearly 50% of right lobe grafts have multiple biliary orifices. Vascular considerations during LDLT are predicated on ensuring adequate inflow and outflow to avoid graft dysfunction. What are the challenges in the living donor living transplant? There are multiple challenges that have precluded the LDLT from becoming more widely adopted. Complications are inevitable in a surgery as complex as the LDLT. The potential for donor-related complications adds a heightened level of sensitivity to the process. Per a longitudinal observational cohort study of 740 hepatectomies from the Adult-to-Adult Living Donor Transplantation Cohort Study consortium, the rate of donor complications is 40% overall, with 1% causing residual disability, liver failure, or death.8 Eighty percent of the complications resolve within 3 months. Biliary complications range from 5%–40% across centers.9 As a result, centers performing high-volume LDLT require expert-advanced endoscopy and interventional radiology departments to address potential complications. Psychiatric complications are a less discussed issue but can occur in up to 14% of donors.1 In 2019, 5 out of the 43 US centers performing LDLT accounted for ~40% of the total volume, illustrating how centralized LDLT remains.10 Centers attempting to start a new LDLT program or increase LDLT volume can be hindered by a relative lack of surgical expertise, infrastructure, and intense scrutiny regarding outcomes. Proposed solutions to these issues include the proctoring of early cases by national experts, the institution of a dedicated multidisciplinary LDLT team, and the risk adjustment for initial cases in UNOS outcomes reporting.10 Lack of awareness among the medical and patient communities remains an obstacle that requires a concerted education effort at the public health and institutional level. Financial disincentives are another issue potentially limiting donors. In a survey of LDLT donors, 37% of donors incurred medical expenses not covered by insurance, and 44% of donors deemed these expenses as a significant financial burden.11 Innovations Innovations to expand the donor pool include ABO-incompatible transplantation, paired exchange, ‘high-risk donors’, and nondirected/altruistic donation. Currently, 10%–20% of LDLTs in Japan and South Korea are ABO-incompatible transplants performed with desensitization protocols with excellent outcomes.7 Liver paired exchange (LPE) refers to a ‘swap’ in which an incompatible donor-recipient pair is matched with another incompatible pair, with a result of 2 compatible pairs if the conditions align. LPE is an effective tool to circumvent issues with ABO incompatibility and donor-recipient size mismatch.12 Utilization of high-risk donors, BMI >30, elderly donors, and borderline GRWR have been expanding as programs have become more adept with LDLT. The nondirected donation, in which the transplantation takes place between a donor unknown to the recipient, tripled between 2010 and 2019 in a study analyzing the UNOS data.11 While the LDLT has traditionally been limited to low MELD recipients in the Western world, in a large single-center study including 1000 patients who underwent LDLT, there was no difference in one-year survival between a low MELD (<25) group versus high MELD (≥25) group.13 Surgical innovations such as laparoscopic donor hepatectomy and robotic donor hepatectomy are promising efforts to further mitigate donor risk. CONCLUSION MELD-based organ allocation is limited by a lack of available organs leading to high waitlist mortality. For LDLT to grow to a greater percentage of total transplants, buy-in at the public health and institutional level will need to take place. Living donor liver transplantation is positioned to be a major part of the solution to help create a more equitable future for liver transplantation (Figure 2).FIGURE 2: Factors required for increased LDLT adoption. Abbreviations: LDLT, living donor liver transplant; ABO-I, ABO-incompatible; ND-LLD, nondirected living liver donation.