Domino liver transplantation: Don't slip in the pool

We read with great interest the case series published by Ekong et al.[1] in which the authors describe their experience in using allografts from 10 patients with maple syrup urine disease (MSUD) during a 5year period ending in 2019. The article describes operative techniques as well as the expected metabolic and survival outcomes of the matched patients with MSUD and the recipients of their domino liver allografts. Domino liver transplantation (DOLT) was first described 25 years ago with the use of liver allografts from patients with familial amyloidotic polyneuropathy (FAP). [2] In the initial series of four patients, the authors described essentially identical technical maneuvers to afford protection to the recipients of both livers. No technical complications were experienced in the patients with FAP and few likely unrelated complications were seen in the recipients of the domino allografts. Since that time, numerous series have been reported with the use of liver allografts from patients with FAP with similar findings. MSUD is an autosomal recessive disease with mutations in one of the subunits of the branched chain ketoacid dehydrogenase complex (BCKDH). Infants are generally diagnosed as part of newborn screening, or with the onset of irritability in the first days of life. Left untreated, further elevations in circulating branched chain amino acids (BCAAs) can rapidly progress to cerebral edema and coma. Dietary restriction of the BCAAs valine, leucine, and isoleucine can halt disease progression but is difficult to maintain, and patients typically have chronic, although sometimes subtle, neurodevelopmental symptoms. As BCKDH activity is constitutively expressed throughout the body, the liver represents only 9%– 13% of the total body enzyme activity. [3– 5] Remarkably, the roughly 10% of normal BCKHD activity found in a transplanted allograft is phenotypically curative for patients with MSUD. [4] In addition, the use of BCKHDdeficient liver allografts from these patients does not alter BCAA metabolism in domino recipients. Thus, MSUD is an ideal disorder in which to consider domino liver transplantation, and large series have documented this since the first experience using a liver from a patient with MSUD as a domino in 2005. [5] The current work confirms many of the findings from articles published during the past decade,[6] but most important it includes data on four young children with MSUD whose explants were used as domino liver allografts by four other children awaiting liver transplantation. The importance of this cannot be underestimated at a time when young children awaiting liver transplantation have the highest risk of death before transplant in the United States, largely because of the overwhelming numerical bias against children on the waiting list. Although living donation and the use of standard technical variant allografts at largevolume centers has stabilized the waitlist mortality rate for children, it is still unacceptably high. Techniques allowing the safe use of even a meager number (18 potential livers over 5 years in this series) of pediatric liver explants as allografts become increasingly important with the relatively small number of additional allografts that would be needed to numerically reduce the mortality rates to zero. The benefit that these patients can offer to other patients waiting for liver transplantation is clear. The ethics surrounding domino donation have been explored in the past, and we would encourage a careful review of that discussion. [7] Although not addressed by Ekong et al.,[1] informed consent for domino donation should be explored after discussion with an independent living (domino) donor advocate at a time remote from the discussion of their candidacy for liver transplantation. A very clear discussion of the operative risks associated with domino donation needs to occur, with attention on the distinct risk associated with organ donation and how that influences the risk of transplantation. Indeed, the authors' description of a “modified” operative technique for patients being used as domino donors highlights the critical need for separate consent so the patient understands that an already technically challenging operation is being modified, not for their own benefit, but for the potential benefit of another unknown recipient. The stakes become even higher for children, who obviously cannot consent on their own. Although one could argue the physiologic impact and potential complications of bicaval versus piggyback reconstruction and circumferential dissection of the cava from the diaphragm, division of a small pediatric hepatic artery below the level of the Received: 5 August 2022 | Accepted: 5 August 2022