Living donor liver transplantation (LDLT) has emerged as a strategy to address the organ shortage, but it can be difficult to find suitable living liver donors (LLDs). The most common reasons why LDLT may not be appropriate are: there is ABO incompatibility between the donor and the recipient‚ implanted liver graft size is too small for the recipient‚ and the potential remnant liver volume is too small for the donor.
Kidney paired exchange (KPE), in which 2 pairs of donors and recipients are matched to allow crossed donation from one pair to the other, was historically established to circumvent ABO/HLA-incompatibility preventing a donor-recipient pair from being transplanted.1 The success of KPE has prompted the consideration of liver paired exchange (LPE). Although the idea seems promising, the actual matching success rate of the initial liver donor exchange program was very low (<1%).2 LPE is inherently more complex and associated with more technical, logistical, and ethical challenges than KPE.3 It has not been easy for both recipient families to agree on the acceptability of the prospective donor’s many variables: age‚ graft size‚ body mass index‚ hepatic steatosis‚ the extent of liver resection‚ and future remnant liver volume. After paired transplantation, depending on the recipient’s complications, it is common to compare recipient outcomes and lay blame on the donor selection. LPE experiences from Asia, like many of the global KPE programs, have performed both pairs of transplants on a single day because of the risk of a donor withdrawing consent. However, in more recent case reports published from the United States, LDLTs in a pair set were performed on consecutive days.4,5 LPE has not expanded at a pace similar to KPE, perhaps because of the lower number of LDLTs performed globally and because donor hepatectomy is inherently more complex and has greater morbidity and mortality compared with donor nephrectomy. Additionally cross-center exchanges are logistically more difficult and have different surgical techniques that make it more difficult to achieve the principle of equity of transplant outcomes.
In this issue of Transplantation, Agrawal et al6 report their experience with an LPE program in India. Two to eight LPEs were performed most years from 2012 to 2021 (with the exception of 2013 and 2015). In total, 34 LPE transplants from 17 pairs of a total of 2340 LDLTs were transplanted, representing 1.45% of transplants during this period. They were divided into R1/D1 and R2/D2 groups and compared. In many centers, it is difficult to use 4 operating rooms simultaneously for 1 LPE, but, in this high-volume center, 2 donor hepatectomies and 2 recipient surgeries were performed at the same time.
There was no living liver donor mortality after donor hepatectomies, but there were 3 serious adverse events (8.8%). Two LLDs exhibited bile leakage, and 1 donor experienced significant posthepatectomy liver dysfunction with an increase in total bilirubin up to 7.3 mg/dL. Five recipients (14.7%) died after LDLT because of sepsis or massive bleeding from surgical complications. The final 30-d and 1-y actual survival rates were 88.2% (n = 30) and 85.3% (n = 29), respectively.
In the past, adult ABO-incompatible (ABOi) LDLTs have been associated with poor graft survival and low patient survival because of hyperacute rejection and a high risk of vascular biliary complications. Various desensitization strategies have been developed to overcome the barrier of ABO incompatibility. Recent noticeable improvements in clinical outcomes after ABOi LDLTs have caused the LPE program to be less attractive than before, resulting in a decreased volume of procedures.2 ABOi LDLTs for adult patients in poor general condition (acute liver failure‚ acute-on-chronic liver failure status‚ or high MELD score), however, have disadvantages compared with ABO-compatible LDLTs because desensitization using rituximab and total plasma exchange are associated with prolonged pretransplant periods during which there is a high risk of sepsis from infection.
Although all LPEs were performed because of ABO incompatibility in this study, a slight expansion of LLDs was observed, increasing annual LDLTs from 0% to 5.3%. Only 52 paired LLDs (0.4%) of 12 371 LLDs from 2002 to 2018 were performed in Korea.7 Desensitization with rituximab and total plasma exchange was used in Korea‚ and‚ reassuringly, there was no difference in bile duct complications, infection, graft failure, patient survival, or hepatocellular carcinoma recurrence after ABOi LDLT compared with ABO-compatible LDLT.8,9 ABOi LDLTs enable LLD pool expansion, increasing LDLT cases in our center by 20%–30% annually (Figure 1). Agrawal et al6 noted that LPE was performed based predominantly on the donor’s anatomical factors, such as the size of partial liver graft (ie, graft-to-recipient weight ratio and percent of future remnant liver volume)‚ and anatomical variations‚ such as arterial, portal, and biliary variants. Although donations were limited by small remnant liver volume in this study, 32 LLDs underwent right hepatectomy‚ and 1 donor underwent extended right hepatectomy. LLDs with future small remnant liver volume should not, in our view, donate unless right posterior liver grafts or left lobe grafts are used. Anatomical difficulties in a specific living liver donor cannot be solved by changing the recipient. However, many anatomical variants in the hepatic artery, portal vein, or bile duct in LLDs are no longer contraindication of living liver donation since these can be overcome using current surgical techniques.
There are advantages to LPE when compared to desensitization‚ such as less intensive immunosuppression requirements‚ better graft outcomes‚ lower infection risk‚ cost savings‚ and the ability to benefit multiple recipients. The registration of more potential pairs increases the number of successful matches, as does the involvement of donors and even compatible pairs.
There are conceptually different incompatibilities and challenges between ABOi LDLTs and LPE LDLTs‚ with successful LPE LDLT requiring the ability to meet a unique set of logistical and ethical challenges. The potential number of LLDs and recipient pairs that may be suitable for LPEs on a global scale is unclear and unexplored at this point in development of the strategies. It is important that the use of both LPE LDLT and ABOi LDLT programs are considered synergistically to increase access to willing LLD.
1. Jackson KR, Segev DL. Rethinking incompatibility in kidney transplantation. Am J Transplant. 2022;22:1031–1036.
2. Jung DH, Hwang S, Ahn CS, et al. Section 16. Update on experience in paired-exchange donors in living donor liver transplantation for adult patients at ASAN Medical Center. Transplantation. 2014;97 (Suppl 8):S66–S69.
3. Mishra A, Lo A, Lee GS, et al. Liver paired exchange: can the liver emulate the kidney? Liver Transpl. 2018;24:677–686.
4. Braun HJ, Torres AM, Louie F, et al. Expanding living donor liver transplantation: report of first US living donor liver transplant chain. Am J Transplant. 2021;21:1633–1636.
5. Patel MS, Mohamed Z, Ghanekar A, et al. Living donor liver paired exchange: a North American first. Am J Transplant. 2021;21:400–404.
6. Agrawal D, Saigal S, Jadaun SS, et al. Paired exchange living donor liver transplantation: a nine-year experience from North India. Transplantation
7. Choi JY, Kim JH, Kim JM, et al. Outcomes of living liver donors are worse than those of matched healthy controls. J Hepatol. 2022;76:628–638.
8. Kim JM, Kwon CHD, Joh JW, et al. ABO-incompatible living donor liver transplantation with rituximab and total plasma exchange does not increase hepatocellular carcinoma recurrence. Transplantation. 2018;102:1695–1701.
9. Kim JM, Kwon CH, Joh JW, et al. Case-matched comparison of ABO-incompatible and ABO-compatible living donor liver transplantation. Br J Surg. 2016;103:276–283.