EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Maple syrup urine disease is characterized by deficient metabolism of branched chain amino acids leading to neurological and developmental delays. Because livers with maple syrup urine disease are histologically normal except for a single enzyme deficiency, which is also present in other organs, liver transplant provides adequate enzymes for metabolism of branched chain amino acids, and the explanted liver can be used as a domino graft for another person needing a liver transplant. We report on the case of a rare individual who survived into adulthood with ante-natal diagnosis and strict dietary management. His recent clinical course was complicated by the development of diabetes mellitus leading to recurrent instances of diabetic ketoacidosis or maple syrup urine disease crisis necessitating liver transplant. Our technical modifications enabled a safe and quick domino hepatectomy by minimizing anesthesia time and the anhepatic phase and timely preparation of the domino graft for an uneventful implantation.

Key words : Branched chain amino acids, Domino liver transplant, Venous outflow reconstruction

Maple syrup urine disease (MSUD) is an autosomal recessive disease characterized by neurological and developmental delay, encephalopathy, feeding problems, accumulation of branched chain amino acids (BCAAs), and a maple syrup odor to the urine.¹ Liver transplant is a curative treatment for MSUD by providing up to 13% of deficient enzyme, which is sufficient for metabolic control. Most patients with MSUD receive a transplant in the first 2 decades.^2-4 The explant is often used for domino transplants, since, barring the deficient enzyme, the liver is otherwise normal in morphology, histology, and function and the recipient has sufficient enzyme activity from nonhepatic sources. Our patient is one of the uncommon survivors without transplant beyond the second decade. He was fortunately diagnosed at birth, and careful management of a protein-restricted diet allowed him to have a relatively normal life until the late third decade when MSUD was complicated by severe type 1 diabetes mellitus, which posed challenges with his carbohydrate-predominant diet. The dual disease occurrence has not been reported in any prior series. The complex dual dietary management for MSUD and diabetes mellitus resulted in repeated hospita-lizations for hypoglycemic episodes and MSUD crisis. This prompted the discussion for liver transplant. Because patients with MSUD in the United States are granted Model for End-Stage Disease (MELD) exception points that enable listing at score 40 if they are domino donors, we decided to perform a domino liver transplant.
Domino liver transplant has specific technical challenges related to recipient hepatectomy because the inflow and outflow need to be preserved until the time of explant as the explanted liver will be used as a domino graft. Safe application of clamps for explantation of native liver and implantation of the new liver is important. The domino graft often has a short suprahepatic cava stump or hepatic vein orifices (caval-sparing hepatectomy) that requires use of specific backtable reconstruction. After comple-ting an evaluation of the patient per protocol, we made a detailed perioperative plan with anesthe-siology, endocrinology, and intensive care providers. Detailed surgical planning for domino graft hepatectomy, implantation of the deceased donor graft in the MSUD recipient, bench preparation of the domino graft, and implantation were done before listing the patient and obtaining the exception points. Here, we have described our technique of using a deceased donor cava graft to enable safe domino hepatectomy and implantation of the domino graft.

Maple syrup urine disease recipient
The MSUD recipient (domino donor) was a 29-year-old male patient with MSUD and type 1 diabetes mellitus. His clinical course was significant for increasing frequency of visits to the emergency department because of metabolic crisis as a result of MSUD, diabetic ketoacidosis, or a combination. His dietary protocol was becoming challenging because of protein restrictions (<25 g/d) combined with low carbohydrate diet. After the patient received intense counseling and preoperative evaluation, he was approved for liver transplant. His perioperative planning involved preparation of a detailed protocol by a multidisciplinary group comprising transplant surgery, hepatology, anesthesiology, metabolic, and adult endocrinology teams. His case was successfully petitioned to the National Liver Review Board for MELD exception points, and he was listed at MELD 40.

Domino graft recipient
The recipient of the domino liver was a 72-year-old male patient with hepatitis C-related cirrhosis and hepatocellular carcinoma (HCC). His hepatitis C virus infection was diagnosed and treated in 2013 until sustained virologic response. He was first diagnosed with HCC in 2020. He had undergone multiple microwave ablations and transarterial chemoembolization for HCC, within Milan criteria, during the past 3 years. He was evaluated and listed for liver transplant. During wait for HCC MELD exception points, he was offered the option of receiving the domino liver graft. He consented to the procedure after multiple discussions with the transplant team.

Pretransplant preparation
The planning for the MSUD recipient included management of sugar and protein intake immediately before going to operating room, while the patient was withholding food and fluids before transplant to avoid fluctuations in BCAA (isoleucine) levels. The vascular anatomy was studied in detail, and the proposed sites of transection of the domino graft hepatic artery and portal vein were decided. Because the graft for the domino MSUD patient was a whole liver from a deceased donor, a bicaval domino hepatectomy was planned to reduce the time needed for dissecting the liver from the inferior vena cava (IVC), to minimize risks of elevated BCAAs and neurological issues during anesthesia, and to preserve a dominant right inferior hepatic vein in the domino graft.

Operative technique
After induction of anesthesia and placement of lines, catheter, and connection to monitoring devices, the MSUD recipient underwent laparotomy with a Mercedes Benz incision. Both lobes of the liver were mobilized from the diaphragm by diving the coronary and triangular ligaments. Bilateral phrenic veins were divided, and phreno-caval tissue was mobilized to gain an extra 2 cm length of the IVC below the diaphragm for safe application of suprahepatic cava clamp (Figure 1A).
The cystic duct was divided, and hilar dissection was done to mobilize the common hepatic duct and hepatic artery. The recipient had a trifurcation pattern of right and left hepatic artery and gastroduodenal artery from the common hepatic artery (CHA); therefore, we mobilized and divided the gastroduo-denal artery to leave a 1-cm segment for the domino graft CHA for recipient implantation (Figure 1, B and C).
The infrahepatic cava was mobilized to enable clamp application at the level of the right suprarenal vein. The portal vein was cleared, and a site 2 cm cranial to the coronary vein was marked for transection. Simultaneously, the standard criteria heart beating deceased donor liver, with no replaced or accessory vessels, was prepared on the bench for bicaval liver implantation.
We proceeded with heparinization by using 5000 units of heparin, and the common bile duct was divided (Figure 1D). We next placed a bulldog clamp on the CHA proximal to the planned transection line and another clamp on the portal vein. An IVC clamp and a suprahepatic clamp were placed. We divided the artery and portal vein and then the infrahepatic cava and the suprahepatic cava, taking care to have adequate stumps for anastomosis for the new liver. The liver was quickly passed to the second bench and flushed with 1 liter of cold saline followed by 3 liters of University of Wisconsin solution.
The implantation of the first graft proceeded as a standard bicaval technique. For suprahepatic cava anastomosis, we used 3-0 Prolene and the eversion technique; for the infrahepatic cava, we used 4-0 Prolene and the eversion technique, avoiding any redundancy. Before completion of anastomosis of the anterior wall of the lower cava, we flushed out the preservative solution by perfusion of the graft portal vein with 1 liter of cold Ringer lactate. The portal vein anastomosis was completed with 6-0 Prolene. The liver was reperfused, and we quickly completed the arterial anastomosis using graft CHA to the reci-pient’s common hepatic artery by using 7-0 Prolene in a continuous manner. The bile duct anastomosis was subsequently completed. No significant reperfusion event occurred, and sugars could be maintained with use of basal insulin without ketosis.
After surgery, the patient was admitted to the intensive care unit. He was extubated on day 1 posttransplant. A low protein diet was started and was gradually advanced to full protein diet by day 4. Blood sugars were managed with insulin drip and converted to combination long and short acting insulin once full oral diet was resumed. Triple immunosuppression with steroid, tacrolimus, and mycophenolate was used with steroid tapered and stopped at 1 month.

Bench preparation of the domino graft
The domino graft was flushed with 3 liters of University of Wisconsin solution through the portal vein. We cleared the portal vein up to the bifurcation. The artery edge and the bile duct stump did not need freshening. The suprahepatic cava on the domino graft was flush with the level of the ostia of hepatic veins. We used a 3-cm segment of the deceased donor IVC as a cylindrical extension (Figure 2, A and B). We used 4 sutures in a quadrangular manner to avoid narro-wing of the hepatic vein orifices at the extension graft anastomosis. The lower end of the domino liver cava was closed with a 3-cm diameter circular patch from deceased donor iliac vein.

Implantation of the domino graft
The recipient’s hepatectomy for the domino graft recipient proceeded uneventfully with careful sepa-ration of prior ablated liver lesions from omentum and diaphragm. We could safely mobilize the liver off the retrohepatic IVC for a caval-sparing explant. We completed the recipient’s hepatectomy, and the implantation was conducted in a piggyback manner. To provide a large outflow and safe stump for suturing of the extension graft, we clamped the supra- and infrahepatic cava and made a large common opening by joining the right and middle plus left hepatic vein orifices (Figure 2C). The enlarged common opening was anastomosed to the domino graft’s extended suprahepatic cava. Preservative solution from the graft was flushed by perfusion of cold lactated Ringer solution through the graft portal vein before completion of the anterior wall of the cava anastomosis. The portal vein anastomosis was completed, and liver reperfusion was uneventful, followed by arterial and bile duct anastomosis. The domino graft recipient had an uneventful recovery. His explant showed a 1.4-cm residual mixed HCC and intrahepatic cholangiocarcinoma with no lympho-vascular or perineural invasion.
The MSUD recipient (the domino donor) and the domino recipient were discharged on day 7 and day 8, respectively, after surgery. The MSUD recipient had no further episodes of ketoacidosis and had normal protein intake with acceptable isoleucine levels at sequential follow-up visits. He experienced an episode of biopsy-proven acute cellular rejection at 3 months, which was treated with steroids, without elevation of serum isoleucine. Both recipients are now 20 months from transplant.

Key technical steps
First, we lengthened the suprahepatic cava by phreno-caval separation and ligation of phrenic veins. Extension of graft was conducted on the suprahepatic cava of the domino graft. Patch closure of the domino graft infrahepatic cava was conducted.

Successful implementation of a domino liver transplant for MSUD and other metabolic disorders has been well-established and reported in the literature.^2-4 The first domino liver transplant was performed by Furtado and colleagues in livers from patients with familial amyloidotic polyneuropathy for patients with liver cancer.⁵ Domino liver transplant presents unique technical challenges, including recon-struction of venous outflow of the domino liver graft and avoidance of outflow issues for both recipients.⁶ Early literature has described the compli-cations associated with the short supra-hepatic cava in the domino graft, including IVC stricture, perioperative Budd-Chiari syndrome, and chylous pericardial tam-ponade due to IVC dissection in the pericardium.^6,7
Various modifications, such as cava-sparing domino hepatectomy and extension of hepatic veins with or without bypass, have been described.⁷ Use of veno-venous bypass has shown problems related to infection at canula insertion sites, lymphocele, thromboembolism, and neurological issues, such as neuropraxia and paresthesia.⁷
Cava-sparing hepatectomy and outflow recons-truction have higher risks of outflow obstruction.^7,8 Of note, the cava-sparing technique is required if the graft for the domino donor is a partial graft or a split graft without accompanying cava. Caval-sparing domino hepatectomy may be used, based on the surgeon’s preference, even if the domino donor receives a whole deceased donor graft, provided that operative time constraints for the retro-hepatic cava dissection are not of particular concern, such as for a domino donor with familial amyloidotic polyneuropathy.^7,8
For our MSUD recipient, our challenge was to minimize the operative time due to risk of MSUD crisis and glycemic control. Hence, hepatectomy with retro-hepatic cava was deliberately planned. The lengthening of the donor suprahepatic cava by ligating the phrenic veins provided an extra 2 cm of subphrenic cava for safe clamping and quick anastomosis. We decided against the use of the deceased donor’s iliac veins as a Y graft, as we surmised that this could have resulted in torsion or kinking and could be a potential site for outflow narrowing due to the different spatial orientation of the right hepatic vein and middle plus left vein orifices where they join the IVC. The lower cava stump of the domino graft was short and had a sizeable inferior vein of 12 mm in diameter less than 5 mm from the lower end. For preservation of this inferior vein, we placed a donor iliac venous circular patch of 3 cm diameter to close the lower end of cava instead of stapling or suture ligating the vein edges.
The use of a cylindrical extension graft on the suprahepatic cava avoided narrowing of the hepatic veins in the domino graft recipient and simplified the second transplant without having to use venous bridging patches between hepatic vein orifices or use of donor iliac vein Y grafts to the right and middle plus left vein openings. Use of donor Y graft is challenging because of the need for the precise measurement and adjustment based on not only the graft configuration but also the body habitus of the domino graft recipient.⁷ If duration of hepatectomy is a concern, even with a partial graft for the domino recipient, such as living donor graft or split graft, then removal of the domino graft with cava followed by reconstruction of the partial graft with a neo cava and a bicaval implantation can ensure a quick and safe hepatectomy and implantation.
The management of the lower end of the cava of the domino graft can be individualized by use of an extension graft for bi-cava anastomosis, ligation, or stapled closure. Another option, as in our case, is patch closure (for preserving inferior vein) for piggyback anastomosis.

We chose a standard bi-caval technique for domino liver hepatectomy to minimize anesthesia time and challenges associated with metabolic management and cerebral edema with anhepatic phase. Our tech-nique of phrenic vein ligation for caval lengthening and use of cava extension graft and patch closure enabled safe and quick domino graft hepatectomy and implantation of the domino liver.

Volume: 23 Issue: 11 November 2025

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