Simultaneous 3-way Paired Exchange Liver Transplantation Without Nondirected Donation: Novel Strategy to Expand the Donor Pool.

ABO incompatibility, donor liver steatosis, and low graft-to-recipient body weight ratio (GRWR) are the most common reasons for rejection of living liver donors. Apart from ABO-incompatible and dual-lobe living-donor liver transplantation (LDLT), the problems of blood group incompatibility and low GRWR can be overcome with paired exchange (PE)-LDLT. PE-LDLT between 2 recipient-donor pairs has been performed at many high-volume centers including ours (experience of 44 pairs to date) for over a decade,1,2 as a strategy to expand the donor pool, by exchanging livers from medically fit donors who are blood group incompatible or have a small-for-size graft for their own relatives. In India, the Human Organ Transplantation Act does not permit nondirected donation3 and allows PE-LDLT only between recipient–donor pairs who are spouses or first-degree relatives. We introduce a concept whereby 3 (or potentially more) such recipient–donor pairs can participate in a chain of transplants, with all the recipients benefitting by either receiving ABO-compatible grafts or adequate GRWR (Figure 1).FIGURE 1.: A, In this example, the paired exchange chain starts with pair 1, with recipient and donor of blood groups AB and B, respectively, where the estimated graft-to-recipient body weight ratio (GRWR) is low. It can involve 5 recipient–donor pairs (blue arrow option), or may stop at 3, and the fourth and fifth pairs can participate in a separate 2-way swap (green dashed arrow option). B, In this example, the paired exchange chain starts with pair 1, with recipient and donor of blood groups B and O, respectively, where the estimated GRWR is low. It can involve 5 recipient-donor pairs (blue arrow option), or may stop at 3, and the fourth and fifth pairs can participate in a separate 2-way swap (green dashed arrow option).We recently performed India’s first 3-way PE-LDLT without a nondirected donor, wherein 2 recipient–donor pairs participated to overcome ABO incompatibility, while in the third pair (recipient AB/donor O blood groups), the estimated GRWR with the right lobe was too low (0.57%) but was adequate for another recipient who sought a blood group–matched donor. Table 1 illustrates how the 3-way PE benefitted all the recipients in the present report. TABLE 1. - How 3-way paired exchange benefitted all the recipients Recipient (R)/blood group R-age, years R-weight, kg Donor (D)/blood group D-age, years D-height, cm D-weight, kg Donor BMI Donor LAI: (liver-spleen attenuation in HU) Donor steatosis TLV, cc RL (excluding MHV), g Left lobe (including MHV), g RL-GRWR% Remnant% R1/AB 51 98 D3/A 31 156 70 28.8 +13 (65–52) Nil 1494 914 580 0.93 38.82 R2/O 58 55 D1/O 49 157 79 32.0 +6 (59–53) Nil 1019 564 455 1.02 44.65 R3/B 31 69 D2/B 29 180 59 18.2 +13 (66–53) Nil 1024 651 373 1.18 36.43 R1/D1 (recipient 1/donor 1) were husband and wife, R2/D2 (recipient 2/donor 2) were mother and son, and R3/D3 (recipient 3/donor 3) were husband and wife.BMI, body mass index; GRWR, graft-to-recipient body weight ratio; LAI, liver attenuation index; MHV, middle hepatic vein; RL, right lobe; TLV, total liver volume. R1/D1 (recipient 1/donor 1) were husband and wife, R2/D2 (recipient 2/donor 2) were mother and son, and R3/D3 (recipient 3/donor 3) were husband and wife. Table 2 shows the recipient and donor pretransplant status and posttransplant outcome parameters. TABLE 2. - Recipient and donor pretransplant status and posttransplant outcome parameters Recipient/donor pair characteristics Recipient 1/AB blood group Donor 3/A Recipient 2/O Donor 1/O Recipient 3/B Donor 2/B Age 51 31 58 49 31 29 BMI 29 28.8 20.37 32 20.57 18.2 Etiology of liver disease NAFLD with HBcAb positive – NAFLD – CRYPTOGENIC – CTP score/MELD score 10/22 – 8/17 – 9/12 – Comorbidity DM, HT Nil DM Nil None Nil KPS 70–80 100 80 100 90 100 Graft WIT/CIT, min 17/80 – 17/86 – 33/120 – Actual GRWR 0.85 – 1.13 – 0.87 – Acute cellular rejection Nil – Nil – Nil – Vascular complications Nil Nil Nil Nil Nil Nil Biliary complications Nil Nil Nil Nil Nil Nil Other complications Intracerebral hemorrhage, managed conservatively Nil Right pleural effusion with underlying consolidation, percutaneous drainage Nil Intra-abdominal collection, percutaneous drainage Nil Length of stay, days 32 5 13 6 11 5 Status at 50 d Discharged, well Well Discharged, well Well Discharged, well Well BMI, body mass index; CIT, cold ischemia time; CTP, Child Turcotte Pugh; DM, diabetes mellitus; GRWR, graft to recipient body weight ratio; HBcAb, hepatitis B core antibody; HT, hypertension; KPS, Karnofsky Performance Status; MELD, Model for End-Stage Liver Disease; NAFLD, nonalcoholic fatty liver disease; WIT, warm ischemia time. A thorough systemic, biochemical, imaging, and psychiatric pretransplant recipient and donor evaluation was performed for all the 3 pairs. As required for all LDLTs in India, an Ethics Committee (Authorization Committee) clearance was duly obtained. All LDLTs were elective, modified right lobe transplants in stable recipients, and donors were all <50 y with no significant hepatic steatosis, and adequate future liver remnant. Two of the recipients and all 3 donors recovered uneventfully. The third recipient suffered a posttransplant hemorrhagic stroke that led to prolonged intensive care unit and hospital stay but is now functionally independent at home with normal liver graft function. A simultaneous 3-way PE-LDLT poses significant ethical, logistic, and technical challenges. The ethical challenge is to ensure fairness in donor safety and recipient outcome for all the participating recipient–donor pairs.4 With regard to logistics and technical expertise, we have a liver operating room complex comprising 6 operating rooms, a team of 19 liver transplant surgeons (9 surgical consultants and 10 fellows), enough trained anesthesiologists, and intensive care unit facilities to simultaneously manage 3 LDLTs perioperatively. Having previously performed 3 LDLTs on the same day a few times, we felt we were adequately equipped and hence proceeded with it. Although all PE-LDLT recipients benefit from the exchange, we try to match the recipients for expected outcomes, such as excluding emergency transplants especially for acute liver failure where outcomes in recipients may not be comparable to elective LDLTs in stable recipients, and families may not have an adequate cooling-off period to understand the implications of their decision. We match potential PE recipient–donor pairs from a database of ABO mismatched pairs, and those with AB recipients or O group donors where the estimated GRWR is <0.7% for sick recipients. In the future, simultaneous intercenter PE-LDLT between experienced, large-volume centers within the same city could be envisaged, using mutually acceptable management protocols. Furthermore, the regulatory procedure for these LDLTs also needs to be defined. Although theoretically possible, nonsimultaneous PE-LDLT may pose potential problems. In 3-way or rare 4-way exchanges done over 2 successive days, the recipient(s) scheduled for the second day may develop infection or acute decompensation necessitating postponement or even make them potentially untransplantable. This would create a disconcerting situation where the donor of such a recipient would have already donated on the first day without realizing any benefit for their own recipient. On the contrary, recipient transplanted on day 1 may not fare well or even die, after which their donor may be reluctant to proceed for donation the following day to complete the exchange. As a proof of concept of a novel strategy to expand the donor pool, we thus report India’s first simultaneous 3-way PE-LDLT without nondirected donation, with good recipient and donor outcomes.