ABO (blood group) incompatibility, donor liver steatosis (fatty liver) and low graft-to-recipient body weight ratio (GRWR) - inadequate volume of partial liver graft from living donor - are the most common reasons for living donors getting rejected for living donor liver transplantation (LDLT). Apart from ABO-incompatible liver transplants, and dual lobe LDLT - wherein partial livers are taken from two donors and transplanted in the recipient - the problems of blood group incompatibility and low GRWR can be overcome with paired exchange LDLT (PE-LDLT).

In 2009, the Medanta Liver Transplant Team introduced the concept of living donor organ swap (or paired exchange) between two recipient-donor pairs. Such exchanges help save lives of recipients whose relatives, despite being medically fit, are unable to donate due to blood group and/or liver size incompatibility.

In India, the Human Organ Transplantation Act does not permit non-directed donation, and allows PE-LDLT only between recipient-donor pairs who are spouses or first-degree relatives. After performing 46 such two-way swaps (92 transplants) over 13 years, the Medanta Liver Transplant Team successfully performed the country’s first three-way liver transplant swap without a non-directed donor recently. Three patients suffering from terminal liver disease received life-saving liver transplants simultaneously. Two 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.

Concept

As shown in the figures below, a three-way, or longer, PE chain can be initiated in LDLT by a recipient-donor pair wherein the recipient’s blood group is AB or the donor’s is O (or both), the estimated GRWR is too low, but adequate for another recipient who seeks a blood-group matched donor.

While longer than three- or four-way chains are logical when Good Samaritan donors initiate it and one of the recipients does not have a live donor, they are often not needed in PE-LDLT. In this case, all recipients contributed a donor to the exchange, and no non-directed donor was involved.

All recipients underwent pre-transplant evaluation, including assessment of severity of liver disease, and detailed systemic, psychiatric, and dietetic assessment. All donors also underwent detailed liver assessment with triphasic contrast enhanced CT scan. Prior to transplant, all LDLTs in India require an Ethics Committee (Authorization Committee) clearance, which was duly obtained for this triple swap as well.

Post-transplant, recipients were managed on triple immunosuppression with tacrolimus, mycophenolate and steroids, and were administered prophylactic antibiotics for five days and fluconazole for 14 days.

Issue 59February 2023

All LDLTs were elective, modified right lobe transplants in stable recipients, and donors were all younger than 50 years with no significant hepatic steatosis, and adequate future liver remnant (FLR). Two of the recipients and all three donors recovered uneventfully. The third recipient suffered a post-transplant hemorrhagic stroke that led to prolonged ICU and hospital stay, but is now functionally independent with normal liver graft function.

A simultaneous three-way PE-LDLT poses significant ethical, logistical and technical challenges. The ethical challenge is to ensure fairness in donor safety and recipient outcome for all the participating recipient-donor pairs. As regards logistics and technical expertise, at Medanta - Gurugram, we have a liver operating room (OR) complex comprising of six ORs, a team of 19 liver transplant surgeons (nine surgical consultants and 10 fellows), enough trained anesthesiologists and ICU facilities

to simultaneously manage three LDLTs peri-operatively. Having previously performed three LDLTs on the same day a few times, we felt we were adequately equipped, and hence proceeded with it.

In future, simultaneous inter-center PE-LDLTs between experienced, large-volume centers within the same city could be envisaged, using mutually acceptable management protocols. Towards this, the regulatory procedure for these LDLTs needs to be defined.

Dr. Arvinder Singh Soin

Liver Transplant

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