Paired Exchange Living Donor Liver Transplantation: A Nine-year Experience From North India : Transplantation

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Original Clinical Science—Liver

Paired Exchange Living Donor Liver Transplantation: A Nine-year Experience From North India

Agrawal, Dhiraj MD, DM1; Saigal, Sanjiv MD, DM, MRCP, CCST1; Jadaun, Shekhar Singh MD, DM1; Singh, Shweta A. MD, DM1; Agrawal, Shaleen MS, MCh1; Gupta, Subhash MS, MCh1

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doi: 10.1097/TP.0000000000004210
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Abstract

INTRODUCTION

Several strategies have been proposed to facilitate living donor liver transplantation (LDLT) for patients with end-stage liver disease. There are several reasons for donor rejection, such as ABO blood group incompatibility (ABOi), inadequate graft-to-recipient weight ratio (GRWR), poor graft quality, difficult liver anatomy, and low remnant liver volume. The problem of low GRWR may be managed by graft inflow modulation or the use of dual-lobe LDLT in the recipient.1 Donor steatosis may be reduced by following a stringent weight loss regimen.2,3 With increasing experience, many centers, including ours, accept donors with anatomical variations.4-6 For ABOi family donors, the need for ABO-incompatible and liver paired exchange (LPE) donation has emerged. The degree of surgical difficulty in ABOi LDLT is not different from compatible transplants but may have inferior long-term patient survival, making LPE a better option.7-10

Although the basic framework for LPE was adopted from the kidney paired exchange program, LPE or swap LDLT is inherently distinct, more complex, and associated with more technical, logistical, and ethical challenges.11 Both recipient and donor surgeries are long-duration surgeries and must be flawless to ensure minimum morbidity and mortality. The living donor partial hepatectomy is associated with approximately 10 times greater mortality than living donor nephrectomy, and the morbidity ranges from 9% to 24%, depending on the type of hepatectomy performed.12,13

The logistics involved in a single-center simultaneous LPE are extensive with 4 simultaneous operations: 4 sets of teams of anesthetists, surgeons, nurses, and technicians. The blood bank must be equipped with requirements for major surges. For a single LDLT operation, it is estimated that >18 skilled team members may be needed, and in LPE, this number is doubled. Furthermore, any unanticipated difficulty due to operative anatomical variations may potentially impact both recipients’ outcomes. These constraints limit the LPE to a few high-volume centers.14-19

Furthermore, there are no models to suggest what would be better for a recipient, a low-GRWR-compatible graft versus good quality, and a high-GRWR-incompatible graft.

Favorable outcomes in LPE require balancing donor risks with excellent recipient survival outcomes with simultaneous operations to avoid the risk of revocation. There have been many publications on LPE, but none have compared the outcomes of the 2 swap pairs in one of the largest series to date.

MATERIALS AND METHODS

Paired Exchange LDLT Program for Adults at “Center for Liver and Biliary Sciences”

This prospective single-center observational study includes 34 consecutive liver-swap transplantations (all directed 2-way exchanges) out of totally 2340 adult LDLTs performed at our center from May 2012 to April 2021. LPE transplantations constituted approximately 1.45% (34 of 2340) of the total LDLT procedures performed at our center during the above-said period. The yearwise paired liver exchanges done are as follows: 2 of 266 (0.75%) in 2012, 0 of 282 (0%) in 2013, 2 of 308 (0.65%) in 2014, 0 of 287 (0%) in 2015, 2 of 259 (0.77%) in 2016, 4 of 205 (1.95%) in 2017, 8 of 222 (3.6%) in 2018, 6 of 227 (2.64%) in 2019, 4 of 171 (2.34%) in 2020, and 6 of 113 (5.3%) in 2021 (till April). All the patients included in the LPE donations were domiciled in India. Written informed consent was obtained from all participants before their inclusion in the study, which was approved by the institutional ethical review board.

Process of Selection of Pairs and Execution of LPE Donations

The goal of our LPE program was to increase LDLT for a subgroup of potentially healthy, willing, first-degree relatives who were not able to do directed liver donations due to ABO incompatibility and/or other factors. The LPE process mainly includes 3 components: registration, manual matching of pairs for equality and suitability, and counseling. We maintained a transplant waitlist registry of a group of incompatible pairs that could be matched when the other appropriate pair came forward. Each incompatible pair was encouraged to perform early registration so that they could arrange finances and prepare the documents required to obtain legal permission.

Equality and simultaneity are the 2 essential principles of our swap living donor program.14 The principle of equality was ensured by matching each donor-recipient pair for donor graft quality, graft size (estimated GRWR >0.8 or a minimum graft volume of 650 g),20,21 medical risk, graft anatomy, and the recipient’s model for the end-stage liver disease (MELD) score. For right lobe (RL) donation, the estimated remnant liver volume was needed to be <30% of total liver volume, and the degree of macrosteatosis should be <30%.22 Left lobe (LL) donation was considered if RL was not feasible. The processes for living donor workup and selection criteria have been described in detail elsewhere.20 The 2 pairs of LDLT operations were performed simultaneously on the same day in the same operating theater complex.

After the recipients and donors of an incompatible pair showed willingness for LPE, the medical suitability of each donor and recipient pair and the equity of the exchange were confirmed by a multidisciplinary forum comprising transplant hepatologists, transplant surgeons, social workers, and psychiatrists. Once 2-by-2 donor-recipient pairs were successfully matched, the transplant team informed the pairs and arranged a meeting wherein each recipient could meet their intended donor in the presence of the transplant team to discuss any anticipated issues. All participants who participated in the exchange program underwent a thorough psychosocial assessment to minimize the possibility of conflict. Donors have clarified that a poor outcome is possible in any LDLT, and in rare circumstances, their intended recipient can have a poor outcome. Through several in-depth counseling sessions, all 4 parties were independently and jointly informed about the suitability and structure of the exchange, the entire procedure, and the expected results. They were also provided with alternative options such as ABOi transplantation, deceased donor liver transplantation (DDLT), and associated risks and cost-effectiveness. Donors were allowed to opt out at any step during the process, and care was taken to avoid coercion. After the development of basic trust between all 4 participants, informed consent and a confidential agreement were signed. In India, there is a strict legal requirement for LDLT that the donor and recipient should be related to either blood or marriage. However, since LPE is an unrelated, directed donation, special approval was obtained from the ethical committee of the local authority.

The LDLT surgical procedures (donor hepatectomy and recipient total hepatectomy), posttransplant management, and postoperative follow-up were identical to those of any other typical adult LDLT.20,23-25 After registration, if the recipients did not undergo LDLT within 6 mo, they were given the option to either continue the LPE waitlist or go ahead with an alternative option such as ABOi LDLT or DDLT.

Statistical Analysis

All numerical data are presented as means with standard deviations or medians with ranges. Graft and patient survival rates were estimated using the Kaplan-Meier method. Recipients (R) and donors (D) of each swap pair were prospectively divided into R1/D1 and R2/D2 groups for comparative and survival analyses. The R1/D1 group had an earlier start and finish of surgery and vice versa. Statistical analysis was performed using the SPSS 14.0 for Windows program (SPSS, Chicago, IL).

RESULTS

ABO Matching Status of the Participants Involved in LPE Donations

The reason for joining the LPE program was ABO incompatibility among all recipients (n = 34). The recipients and donors had equal numbers of ABO blood group types A (n = 17) and B (n = 17), respectively. At the onset, the ABO blood group matching status in donors and recipients was A to B in 17 pairs (50%) and B to A in 17 pairs (50%). After 2-by-2 directed liver exchange donations, the ABO matching status changed from A to A (n = 17) and B to B (n = 17). This resulted in all ABO-compatible matches, as demonstrated in Figure 1. At the time of writing the article, the LPE registry had >4 ABOi pairs with A and B donors, and vice versa, waiting for LDLT.

F1
FIGURE 1.:
Concept of paired exchange LDLT/swap LDLT. LDLT, living donor liver transplantation.

Living Donor Profiles

The 17 pairs of LPE donations included 34 directed living donors with a median age of 38.5 y (19–51 y), of which 27 were females. All donors were first-degree relatives of the recipients and included 18 spouses, 11 children, and 5 siblings. The baseline characteristics of donors are presented in Table 1. The median hospital stay after donor hepatectomy surgery was 9 d (range, 7–20 d). One donor (pair set 3/D2) had large droplet macrovesicular steatosis of 25%–30% at the initial liver biopsy. With diet and exercise for 3 mo, he showed rapid reversal of liver steatosis and successfully underwent LPE donation. One of the donors had total core hepatitis B (HBcAg) positivity, and the recipient received lamivudine for the same postoperatively, although he had high anti-HBsAg antibody titers. Two donors (pair set 9/D2 and 14/D2) had a short-duration bile leak, which did not require any intervention. The HIDA scan performed on postoperative day (POD) 7 was normal, and both donors were discharged on POD 9. One donor (pair set 5/D1) developed postdonor hepatectomy liver dysfunction with a peak bilirubin of 7.3 mg/dL on POD 9. The patient was discharged on POD 20 with a total bilirubin 2.2 mg/dL and international standardized ratio 1.1. The remaining donors have had an uneventful course to date. Thus, donor morbidity was 8.8% (n = 3), and donor survival was 100%.

TABLE 1. - Characteristics of donors involved in liver paired exchange donations (n = 34)
Donor parameters (median) Results, N (%/range)
Liver paired exchange donations 34
Reason for LPE donations ABO incompatibility (34 [100%])
Blood group A/B 17/17
Female sex/age (y) 27 (79%)/38.5 (19–51)
BMI (kg/m2) 24.61 (18.3–34.6)
LAI 9.8 (−4 to 25)
MR fat fraction (%) 3 (1–14.5)
Right lobe volume without MHV (g) 775 (561–1015)
Left lobe volume with MHV (g) 461 (309–880)
FLR (%) 38 (31–46)
Liver graft used for donation
MRL a 32 (94%)
LL graft 1 (3%)
ERL 1 (3%)
Portal vein anatomy
Type 1 33 (97%)
Type III 1 (3%)
Biliary anatomy (on MRCP) b
Type 1 21 (62%)
Type II 1 (3%)
Type IIIa 7 (21%)
Type IIIb 3 (9%)
Type VI (2 right-sided ducts) 2 (6%)
Hospital stay s/p donor hepatectomy (d) 9 (7–20)
Donor morbidity/mortality 3 (8.8%)/0
aModified right lobe graft—MHV venous tributaries from the right anterior sector are preserved and are reconstructed on the back table with interposition vascular grafts26.
bBiliary classification was performed as described by Huang et al27 and Choi et al.28
BMI, body mass index; ERL, extended right lobe; LAI, liver attenuation index; LL, left lateral; LPE, liver paired exchange; MHV, middle hepatic vein; MR, magnetic resonance; MRCP, magnetic resonance cholangiopancreatography; MRL, modified right lobe; s/p, status post.

Recipient Profiles

All recipients underwent LDLT simultaneously. The detailed profile of the recipients (n = 34; median age, 45.5 y [11–59 y]; 31 men) is shown in Table 2. Of 34 swap liver recipients, 33 were adults and 1 was an 11-y-old boy with progressive familial intrahepatic cholestasis. Three patients (9%) had hepatocellular carcinoma (HCC) based on the University of California, San Francisco (UCSF), criteria. Two patients with acute cellular rejection responded to IV pulse steroid therapy. Posttransplant explants (pair set 3/R1) showed noncaeseating epithelioid granulomas and peritoneal tuberculosis. Rifabutin-based antituberculous therapy was initiated after the normalization of liver function tests. Five patients required reexploration.

TABLE 2. - Characteristics of recipients involved in paired exchange LDLT (n = 34)
Parameters (median/range) Results, N (%)
Age (y) 45.5 (11–59)
Standard MELD score 21 (10–36)
CTP score 10 (5–14)
Male sex/age (y) 31 (91%)/45.5 (11–59)
BMI (kg/m2) 24.75 (12.9–38.1)
Primary diagnosis in recipients N/%
Alcoholic liver cirrhosis 17 (50%)
Cryptogenic liver cirrhosis 6 (17.65)
HCV-associated liver cirrhosis 5 (14.7%)
Hepatitis B virus–associated liver cirrhosis 2 (5.9%)
NASH-related cirrhosis 1 (2.9%)
PFIC 1 (2.9%)
AIH-related cirrhosis 1 (2.9%)
Combined HCV-associated and alcoholic liver disease 1 (2.9%)
Hepatocellular carcinoma 3 (9%)
Graft weight (g) 746 (400–984)
GRWR 1.04 (0.63–2.2)
Warm ischemia time (min) 34.5 (12–54)
Cold ischemia time (min) 98.5 (51–321)
Posttransplant ICU stay (d) 13 (5–42)
Posttransplant hospital stays (d) 20.5 (5–65)
Posttransplant complications
Intra-abdominal bleeding 1 (5.9%)
Bile leak 2 (5.9%)
Acute rejection 2 (5.9%)
Hepatic artery thrombosis 1 (2.9%)
Hepatic vein thrombosis 3 (8.8%)
Sepsis 7 (14.7%)
Delayed graft uptake 1 (2.9%)
Acute kidney injury 10 (29.4%)
Gastrointestinal bleed 1 (2.9%)
Pleural effusion 1 (2.9%)
Wrist drop 1 (2.9%)
Ventricular tachycardia 1 (2.9%)
Heparin induced thrombocytopenia 1 (2.9%)
Tacrolimus-related neurotoxicity 3 (8.8%)
MMF-induced diarrhea 3 (8.8%)
MMF-induced leucopenia 2 (5.9%)
Reexploration 5 (14.7%)
Early mortality (within 1 mo) 4 (11.8%)
1-y survival 29 (85.3%)
Median follow-up in mo (IQR) 27 (8–43)
Overall survival 29 (85.3%)
AIH, autoimmune hepatitis; BMI, body mass index; CTP, Child Turcott Pugh; GRWR, graft-to-recipient weight ratio; HCV, hepatitis C virus; ICU, intensive care unit; IQR, interquartile range; LDLT, living donor liver transplantation; MELD, model for end-stage liver disease; MMF, mycofenolate mofetil; NASH, nonalcoholic steato hepatitis; PFIC, progressive familial intrahepatic cholestasis.

Five patients (14.7%) succumbed in postoperative period. A pair of 3/R2 patients with hepatitis C-related cirrhosis developed hepatic artery thrombosis with bile leak and intra-abdominal sepsis. She underwent exploratory laparotomy on POD 20 with hepatic arterial balloon dilatation and primary thrombolysis with hepatic artery stenting. The patient died after a prolonged hospital stay of 42 d. Both the recipients (R1 and R2) of pair set 5 and the R2 recipient of pair set 7 died of intra-abdominal sepsis and multiorgan failure on POD 6, POD 8, and POD 3, respectively. A pair of 16/R2 patients had pretransplant Yerdel’s II portal vein thrombosis for which eversion thrombectomy was performed. The patient developed intra-abdominal bleeding with compartment syndrome, which required exploratory laparotomy. The patient succumbed to multiorgan failure on POD 3. The 30-d and 1-y survivals were 88.2% (n = 30) and 85.3% (n = 29), respectively. The overall recipient survival was 85.3% (n = 29) over a median follow-up period of 27 mo (1–108 mo).

The comparative survival analyses between the R1 and R2 groups are shown in Table 3. The baseline clinical and perioperative parameters, postoperative complications, median intensive care unit (ICU)/hospital stay, and early death were statistically comparable (P > 0.1) between the R1 and R2 groups. Posttransplant survival is shown with a Kaplan-Meier curve in Figure 2.

TABLE 3. - Recipient characteristics and comparative data between R1 and R2 groups of paired exchange LDLT (n = 34)
Parameters (median/range) Total R (n = 34) R1 (n = 17) R2 (n = 17) P
Age (y) 45.5 (11–59) 44.0 (±10.1) 47.0 (±5.3) 0.296
Standard MELD score 21 (10–36) 21.8 (±11.1) 19.4 (±6.3) 0.445
CTP score 10 (5–14) 9.5 (±2.3) 10.3 (±2.1) 0.294
Graft weight (g) 746 (400–984) 711 (±141.2) 796 (±119.8) 0.067
GRWR 1.04 (0.63–2.2) 1.01 (±0.34) 1.18 (±0.26) 0.136
Warm ischemia time (min) 34.5 (12–54) 32.7 (±7.8) 36.1 (±7.1) 0.257
Cold ischemia time (min) 98.5 (51–321) 109.7 (±61.2) 112.6 (±40.9) 0.870
ICU stay (d) 13 (5–42) 12.4 (±4.6) 14.4 (±10.5) 0.654
Hospital stays (d) 20.5 (5–65) 16.7 (±4.6) 21.6 (±4.7) 0.197
Complications, n (%)
Bleeding 1 0 1 (5.9%) 1.00
Bile leak 2 0 2 (11.8%) 0.485
Acute rejection 2 1 (5.9%) 1 (5.9%) 1.00
Hepatic artery thrombosis 1 0 1(5.9%) 1.00
Hepatic vein thrombosis 3 2 (11.8%) 1(5.9%) 0.542
Sepsis 7 2 (11.8%) 5 (29.4%) 0.398
Early mortality (within 1 mo) 4 1 (5.8%) 3(17.6%) 0.601
1-y survival 29 16 (100%) 13 (92.8%) 0.335
Median follow-up in mo (IQR) 27 (8–43) 27 (8–39) 27 (8–43) 1.00
CTP, Child Turcott Pugh; GRWR, graft-to-recipient weight ratio; ICU, intensive care unit; IQR, interquartile range; LDLT, living donor liver transplantation; MELD, model for end-stage liver disease; R, recipient.

F2
FIGURE 2.:
Kaplan-Meier curve demonstrating the posttransplant survival in the R (n = 34), R1 (n = 17), and R2 (n = 17) group. R, recipient.

DISCUSSION

With the strict legal requirement for donors and recipients to be related to either blood or marriage, unless blood group barriers are overcome, the number of LDLTs will not increase. Early experience from South Korea has shown that paired exchange LDLT is a fair and legal method to increase the donor pool without compromising recipient outcomes.14,15 Center for Liver and Biliary Sciences is a large-volume center with significant LDLT experience that adopted an ABO-incompatible and swaped LDLT program early in 2012. As our program matured, the number of ABO-incompatible and paired donor exchange LDLTs rapidly increased.

ABOi LDLT requires a period of preparation that is usually 2 wk and is more expensive, and the long-term survival may be affected by the development of diffuse intrahepatic biliary strictures.7,29-31 Hence, paired donor exchange LDLT may be preferable over ABOi LDLT; however, LPE is not possible when the donor has blood group O or the recipient has blood group AB, as in both situations, paired exchange is not mutually beneficial. Donors with the A2 subtype of blood group A are unique in that they have diminished expression of A antigen, and the intended liver recipient is considered to require minimal pretransplant immunomodulation. Hence, theoretically, like type O blood group donors, type A2 donors can lead to ABO-compatible liver transplants with minimal immune rejection. Such A2 to B donation is well recognized in kidney transplantation but is rare in LDLT.32 Although in our series, all patients underwent LPE for ABO incompatibility, paired exchange can be performed for a variety of other indications, such as low GRWR, small remnant liver, and anatomical variations. Hwang et al14 and Jung et al15 reported that only 4 out of 26 LPE cases over a 9-y period (2182 LDLTs) were performed for nonblood group indications.

ABO-incompatible donor-recipient pairs are encouraged to visit our center regularly, and as this is a common problem, not surprisingly, they are often able to meet another ABOi pair at the center. Furthermore, our coordinators have the telephone numbers of recipients looking for paired exchanges, and they facilitate such pairs to speak to each other on the phone. Once they show willingness to participate in the paired exchange program, their papers are submitted to the government-appointed authorization committee for clearance. Theoretically, in LPE donations, there is a potential for emotional disconnect, as opposed to ABO-incompatible LDLT. Interestingly, in our series of 34 transplants, the donor felt that they had donated to their own recipient, and on follow-up, all 4 participants seemed to have developed great emotional bonding.

At our center, >75% of donors are first-degree relatives as “nonnear relatives” find very difficult to get governmental clearance. LPE is a transplantation between unrelated people and is, therefore, liable for exploitation. However, The Transplant Act has built in safety features as it allows only “first degree relatives” to be considered for paired exchange and also bars the organ exchanges between Indian and foreigners.

The logistical challenge with a simultaneous single-center–directed LPE donation is that all 4 operations must be conducted on the same day. Therefore, the transplant team should consist of 4 senior surgeons, anesthetists, OT technicians, and nurses. As most centers do not have such large teams, senior surgeons will often have to rotate from one operating room to another to ensure the smooth conduct of all 4 operations. Once the 2 transplantation surgeries were started simultaneously, their progress was independent. In simultaneous LPE, it is possible that one of the recipients may receive less attention in the operating room; hence, this study was conducted to determine whether the outcome was different in the 2 pairs. As shown through the R1/R2 comparison, the outcome of LPE recipients was not influenced by the logistics and technical challenges encountered in simultaneously performing 2 LDLT operations. In our study, the CIT was 109.7 versus 112.6 min, and the warm ischemic times were 32.7 versus 36.1 min, suggesting that neither of the pair had an inferior operation. The operative durations for both surgeries were comparable, although the start and finish times for recipient surgeries were different. A recent case report of the first sequential LPE from the United States, where LPE was initiated by a nondirected donor and was performed over the course of 2 consecutive days and relied on the use and compliance of a bridge donor.19 Some transplant centers in the West have reported sequential paired kidney exchanges.33 We cannot perform LPE sequentially or one after another on the same day, as each LDLT operation takes over 16 h. Doing so on different days can be a solution, but our hospital will not allow this to happen due to a possible risk of revocation. Our society is not mature enough for this to take place, as donation is completely voluntary and the donor can withdraw consent at the last minute with no legal recourse. In fact, the transplant team is responsible for maintaining the interests of both pairs. It is possible that, in the future, transplant centers in India will act in tandem, and we will be able to operate pairs at 2 different centers. However, under the existing hospital-based government-appointed authorization committee, this may not be feasible unless a central clearing agency is set up.

In LPE, there is not only the stress of multiple simultaneous operations but also the need to provide excellent outcomes, as even with 1 posttransplant death, the team has to deal with 4 families, which can sometimes be quite stressful. We deal with this by counseling on multiple occasions and stressing to the families that 1-y survival is 85% at our center, and in difficult situations, patient keenness and risk understanding must be there. In one instance, the recipient had pretransplant dilated cardiomyopathy with global LV hypokinesia and low ejection fraction of 35% (pair set 17/R2). In the Transplant Board meeting, there was a suggestion that the patient should not undergo transplantation. However, as the donor characteristics were excellent and the patient had been looked after successfully by us on multiple occasions, the patient was very keen to go ahead with the transplant. Fortunately, the recipient recovered after a prolonged hospital stay.

The indications for liver transplantation in paired exchange should follow accepted guidelines and should be similar to the acceptable practice in DDLT. For example, transplants are often considered for HCC outside the Milan/UCSF criteria in LDLT; however, this would not be suitable in paired exchange LDLT to provide similar outcomes in both pairs. Three recipients (9%) in our study had HCC; however, all were within UCSF criteria, and none of them had recurrence to date. Our recipients had advanced liver disease (median MELD score, 21 [10–36]) with sufficient reserve to wait for 1–2 mo for an opposing pair to become available. In recent publications, patients with ACLF grade 3 have had >85% 1-y survival. Frailty and malnourishment have been thought to be adverse prognostic factors.34 With this background, it is often not possible to scientifically reject high-risk candidates.

For exchange LDLT, the principle of equality requires that neither recipient be disadvantaged. The outcome of the recipient is also affected by donor characteristics such as graft size, graft quality, and biliary anatomy. Donor selection was strictly based on our current protocol and was only approved if it matched the potential recipient without considering the benefit of the other recipient. Donors with an estimated GRWR >0.8 (median GRWR was 1.04 [0.63–2.2]) were preferred, and when it was lower, a minimum graft volume of 650 g was essential, as has been shown in our previous study by Agarwal et al.21 It was not surprising that in our study, although 3 patients had GRWR <0.8, none of these recipients developed small for size syndrome as their graft volume exceeded 650 g.

Another ethical consideration in paired exchange is that both donor operations should be of similar magnitude and do not pose a higher risk to one of the donors. A deficiency in liver transplantation practice is that no accurate model exists to predict donor outcomes after transplantation. The donor risk index has been used to predict outcomes but has limited applicability.35 Although, in the past, LL donations have been thought to have lower risk compared with RL donations,20 recent publications as well as our experience suggest that the risks are comparable.36

As a result, the mother underwent RL donor hepatectomy in exchange for a left lateral segment graft from a 19-y-old donor for her 12-y-old child. In this altruistic case, both organ donation surgeries involved unequal donor risk but were equally lifesaving. These 2 Samaritan donor operations were not bound by the need for comparability in donor risks.

In our study, the majority of donors were women, majority of recipients were men, and alcoholic liver disease was the most common indication for LPE (50% [n = 17]). A surprising finding in our center was that spouses of those suffering from alcoholic liver disease still came forward for donation without any coercion, even when the risk of recidivism was overstressed. Overall, donor morbidity was 8.8% (n = 3), and all had Dindo-Clavien grade 1 complications that resolved completely. Five out of 34 recipients died, and the 1-y recipient survival was 85.3%. In only 1 case, death could be attributed to surgery per se, as the recipient bled massively after portal vein thrombectomy.

We report one of the largest series to date of 34 swap LDLTs with a 27-mo patient and graft survival rate of 85% from India. Our keys to success were creating a platform for registration for paired exchange transplants, increasing the awareness of all transplant professionals, active counseling programs, and developing a large inhouse transplant team. As shown in this report, a simultaneous, single-center, 2-way directed paired liver exchange donation is completely feasible at centers with significant LDLT experience.

Although challenging, this is an exciting new access to donor organs for patients in need and can facilitate a greater number of LDLTs.

REFERENCES

1. Chen Z, Yan L, Li B, et al. Prevent small-for-size syndrome using dual grafts in living donor liver transplantation. J Surg Res. 2009;155:261–267.
2. Choudhary NS, Saraf N, Saigal S, et al. Rapid reversal of liver steatosis with life style modification in highly motivated liver donors. J Clin Exp Hepatol. 2015;5:123–126.
3. Trakroo S, Bhardwaj N, Garg R, et al. Weight loss interventions in living donor liver transplantation as a tool in expanding the donor pool: a systematic review and meta-analysis. World J Gastroenterol. 2021;27:3682–3692.
4. Watson CJ, Harper SJ. Anatomical variation and its management in transplantation. Am J Transplant. 2015;15:1459–1471.
5. Kasahara M, Egawa H, Takada Y, et al. Biliary reconstruction in right lobe living-donor liver transplantation: comparison of different techniques in 321 recipients. Ann Surg. 2006;243:559–566.
6. Yaprak O, Dayangac M, Akyildiz M, et al. Biliary complications after right lobe living donor liver transplantation: a single-centre experience. HPB (Oxford). 2012;14:49–53.
7. Egawa H, Teramukai S, Haga H, et al. Present status of ABO-incompatible living donor liver transplantation in Japan. Hepatology. 2008;47:143–152.
8. Matsuno N, Nakamura Y, Mejit A, et al. Long-term follow-up ABO-incompatible adult living donor liver transplantation in cirrhotic patients. Clin Transplant. 2007;21:638–642.
9. Toso C, Al-Qahtani M, Alsaif FA, et al. ABO-incompatible liver transplantation for critically ill adult patients. Transpl Int. 2007;20:675–681.
10. Usui M, Isaji S, Mizuno S, et al. Experiences and problems pre-operative anti-CD20 monoclonal antibody infusion therapy with splenectomy and plasma exchange for ABO-incompatible living-donor liver transplantation. Clin Transplant. 2007;21:24–31.
11. Mishra A, Lo A, Lee GS, et al. Liver paired exchange: can the liver emulate the kidney? Liver Transpl. 2018;24:677–686.
12. Lo CM. Complications and long-term outcome of living liver donors: a survey of 1,508 cases in five Asian centers. Transplantation. 2003;75:S12–S15.
13. Ghobrial RM, Freise CE, Trotter JF, et al.; A2ALL Study Group. Donor morbidity after living donation for liver transplantation. Gastroenterology. 2008;135:468–476.
14. Hwang S, Lee SG, Moon DB, et al. Exchange living donor liver transplantation to overcome ABO incompatibility in adult patients. Liver Transpl. 2010;16:482–490.
15. 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.
16. Chan SC, Lo CM, Yong BH, et al. Paired donor interchange to avoid ABO-incompatible living donor liver transplantation. Liver Transpl. 2010;16:478–481.
17. Chan C, Chok KSH, Sharr WW, et al. Samaritan donor interchange in living donor liver transplantation. Hepatobiliary Pancreat Dis Int. 2014;13:105–109.
18. Patel MS, Mohamed Z, Ghanekar A, et al. Living donor liver paired exchange: a North American first. Am J Transplant. 2021;21:400–404.
19. 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.
20. Hwang S, Lee SG, Lee YJ, et al. Lessons learned from 1,000 living donor liver transplantations in a single center: how to make living donations safe. Liver Transpl. 2006;12:920–927.
21. Agarwal S, Selvakumar N, Gupta S, et al. Minimum absolute graft weight of 650 g predicts a good outcome in living donor liver transplant despite a graft recipient body weight ratio of less than 0.8. Clin Transplant. 2019;33:e13705
22. Fan ST, Lo CM, Liu CL, et al. Determinants of hospital mortality of adult recipients of right lobe live donor liver transplantation. Ann Surg. 2003;238:864–870.
23. Hwang S, Lee SG, Ha TY, et al. Simplified standardized technique for living donor liver transplantation using left liver graft plus caudate lobe. Liver Transpl. 2004;10:1398–1405.
24. Lee S, Park K, Hwang S, et al. Anterior segment congestion of a right liver lobe graft in living-donor liver transplantation and strategy to prevent congestion. J Hepatobiliary Pancreat Surg. 2003;10:16–25.
25. Lee SG, Park KM, Hwang S, et al. Adult-to-adult living donor liver transplantation at the Asan Medical Center, Korea. Asian J Surg. 2002;25:277–284.
26. Lee SG. (2019) Modified right-lobe graft. Oniscu GC, Forsythe JLR, Pomfret EA, eds. In: Transplantation Surgery. Springer Surgery Atlas Series. Springer. Available at https://doi.org/10.1007/978-3-540-73796-4_12.
    27. Huang TL, Cheng YF, Chen CL, et al. Variants of the bile ducts: clinical application in the potential donor of living-related hepatic transplantation. Transplant Proc. 1996;28:1669–1670.
    28. Choi JW, Kim TK, Kim KW, et al. Anatomic variation in intrahepatic bile ducts: an analysis of intraoperative cholangiograms in 300 consecutive donors for living donor liver transplantation. Korean J Radiol. 2003;4:85–90.
    29. Egawa H, Tanabe K, Fukushima N, et al. Current status of organ transplantation in Japan. Am J Transplant. 2012;12:523–530.
    30. Wu J, Ye S, Xu X, et al. Recipient outcomes after ABO-incompatible liver transplantation: a systematic review and meta-analysis. PLoS One. 2011;6:e16521.
    31. Gi-Won Song, Sung-Gyu Lee, Nayoung Kim, et al. Biliary stricture is the only concern in ABO-incompatible adult living donor liver transplantation in the rituximab era. J Hepatol. 2014;61:575–82.
    32. Puri Y, Rammohan A, Sachan D, et al. ABO-incompatible living donor liver transplant from a blood type A2 donor to a type B recipient: a note of caution. Exp Clin Transplant. 2022;20:100–103.
    33. Yu YD, Hwang R, Halazun KJ, et al. Whose liver is it anyway? Two centers participating in one living donor transplantation. Liver Transpl. 2019;25:1710–1713.
    34. Sundaram V, Jalan R, Wong RJ, et al. Factors associated with survival of patients with severe acute-on-chronic liver failure before and after liver transplantation. Gastroenterology. 2019;156:1381–1391.e3
    35. Feng S, Goodrich NP, Bragg-Gresham JL, et al. Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant. 2006;6:783–790.
    36. She WH, Chok KSH, Fung JYY, et al. Outcomes of right-lobe and left-lobe living-donor liver transplantations using small-for-size grafts. World J Gastroenterol. 2017; 23: 4270–4277.

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