Domino Liver Transplantation Research Articles

P.348: Split left and right liver transplantation plus domino liver transplantation: one donor liver and three recipients at the same time, a complex but feasible allocation scheme to alleviate donor liver shortage.

P.348: Split left and right liver transplantation plus domino liver transplantation: one donor liver and three recipients at the same time, a complex but feasible allocation scheme to alleviate donor liver shortage.

364.13: Life-saving liver transplant procedure for pediatric and adult patients: Domino liver transplantation.

364.13: Life-saving liver transplant procedure for pediatric and adult patients: Domino liver transplantation.

Highly sensitized patients listed for heart after liver transplantation with or without domino

For patients with end stage heart disease and borderline hemodynamics, high HLA allosensitization presents a barrier for heart transplantation in a timely manner. Conventional desensitization protocols are inadequate in this context due to time constraints and for the most highly reactive immunologically. We previously reported performing heart after liver transplant with domino liver transplant (HALT-D) on a single patient without liver disease. We describe this patient's course to date as well as four subsequent patients listed for this novel therapy. This experience demonstrates that the liver effectively confers immunoprotection to the heart for patients with high-titer, preformed antibodies. This strategy may provide some measure of equity for demographic groups previously disadvantaged for heart transplantation due to allosensitization.

Perioperative management in pediatric domino liver transplantation for metabolic disorders: A narrative review.

Domino liver transplantation and domino-auxiliary partial orthotopic liver transplantation are emerging techniques that can expand the liver donor pool and provide hope for children with liver disease. The innovative technique of domino liver transplantation has emerged as a pioneering strategy, capitalizing on structurally preserved livers from donors exhibiting single enzymatic defects within a morphologically normal context, effectively broadening the donor pool. Concurrently, the increasingly prevalent domino-auxiliary partial orthotopic liver transplantation method assumes a critical role in bolstering available donor resources. These advanced transplantation methods present a unique opportunity for pediatric patients who, despite having structurally and functionally intact livers and lacking early signs of portal hypertension or extrahepatic involvement, do not attain priority on conventional transplant lists. Utilizing optimal clinical conditions enhances posttransplant outcomes, benefiting patients who would otherwise endure extended waiting periods for traditional transplantation. The perioperative management of children undergoing these procedures is complex and requires careful consideration of some factors, including clinical and metabolic conditions of the specific metabolic disorder, and the need for tailored perioperative management planning. Furthermore, the prudent consideration of de novo disease development in the recipient assumes paramount significance when selecting suitable donors for domino liver transplantation, as it profoundly influences prognosis, mortality, and morbidity. This narrative review of domino liver transplantation will discuss the pathophysiology, clinical evaluation, perioperative management, and prognostic expectations, focusing on perioperative anesthetic considerations for children undergoing domino liver transplantation.

Safety, Tolerability, and Outcomes of Tafamidis for the Treatment of Acquired Amyloid Neuropathy in Domino Liver Transplant Recipients.

Acquired amyloid neuropathy is an iatrogenic disease that appears years after a domino liver transplant. The objectives of our study are to analyze the efficacy and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. This post-authorization, prospective, longitudinal study included seven domino liver transplant recipients with acquired amyloid neuropathy who received treatment with tafamidis for 18months. The primary endpoints were the response rate, defined as those patients with an increase of<2 points on the Neurological Impairment Score (NIS) from baseline, and the change in the NIS score from baseline. Secondary endpoints included the Quantitative Sensory Test, 10-m walk test, quality of life (Norfolk), and disability (Rasch-built Overall Disability Scale). As safety parameters, the evidence of graft rejection, changes in immunosuppressive trough levels and changes in antiviral and allogeneic cellular immunity before and 12months after tafamidis treatment were also assessed. Six patients (85.7%) had responded at 18-months. Compared to baseline, we observed non-statistically significant improvement in mean NIS score at 6months (- 2.54 points, CI - 5.92 to 0.84), 12months (- 3.25 points; CI - 6.63 to 0.13), and 18months (- 2.35 points; CI - 5.74 to 1.02). Changes in the Quantitative Sensory Test, 10-m walk tests and the quality of life and disability questionnaires were not statistically significant. The use of tafamidis did not induce relevant side effects or drug interactions. Also, no acute rejections events nor changes in functional adaptive immunity were observed. Our study supports the safety and tolerability of tafamidis for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. Tafamidis shows promise as a useful treatment in the clinical management of these patients. Future randomized placebo-controlled clinical trials with longer follow-up durations are needed.

Technical Challenges in Simultaneous Living Donor Liver Transplantation and Domino Orthotopic Liver Transplantation

Liver transplantation is the ideal treatment of choice for Familial amyloid polyneuropathy (FAP). It is known that during transplantation surgery, this explant liver which will be removed from amyloid patient can be used as a domino graft for another suitable recipient. Even after successful results of domino liver transplantation in deceased donation setting this procedure is always seen with a fear of putting both the recipients at risk due to technical challenge. With living donor as the liver donor for the amyloid patient, the challenges faced are even higher. Only few centres have done similar surgeries and there are no standard guidelines for the same. The anatomical prerequisites, technique, and indications of domino orthotopic liver transplant (D-OLT) in live donation settling are still evolving. We here report a case of live donor liver transplant from a 38 year old with a Right lobe graft for a 40 year old with FAP along with D-OLT for a 52 year old with HBV related decompensated chronic liver disease with HCC. We have described the technical challenges and learnings in our first case which is one of few cases done in the Indian Subcontinent.

Clinical outcomes after transplantation of domino grafts or standard deceased donor livers: a systematic review and meta-analysis.

Domino liver transplantation (DLT) utilizes otherwise discarded livers as donor grafts for another recipients. It is unclear whether DLT has less favorable outcomes compared to deceased donor liver transplantation (DDLT). We aimed to assess the outcomes of DLT compared to DDLT. MEDLINE, Embase, and Web of Science database were searched to identify studies comparing outcomes after DLT with DDLT. Data were pooled using random-effects modeling, evaluating odds ratios (OR) or mean difference (MD) for outcomes including waiting list time, severe hemorrhage, intensive care unit (ICU), length hospital stay (LOS), rejection, renal, vascular, and biliary events, and recipient survival at 1, 3, 5, and 10years. Five studies were identified including 945 patients (DLT=409, DDLT=536). The DLT recipients were older compared to the DDLT group (P=0.04), and both cohorts were comparable regarding lab MELD, hepatocellular carcinoma, and waitlist time. There were no differences in vascular (OR: 1.60, P=0.39), renal (OR: 0.62, P=0.24), biliary (OR: 1.51, P=0.21), severe hemorrhage (OR: 1.09, P=0.86), rejection (OR: 0.78, P=0.51), ICU stay (MD: 0.50, P=0.21), or LOS (MD: 1.68, P=0.46) between DLT and DDLT. DLT and DDLT were associated with comparable 1-year (78.9% vs 80.4%; OR: 1.03, P=0.89), 3-year (56.2% vs 54.1%; OR: 1.35, P=0.07), and 10-year survival (6.5% vs 8.5%; OR: 0.8, P=0.67) rates. DLT was associated with higher 5-year survival (41.6% vs 36.4%; OR: 1.70; P=0.003) compared to DDLT, which was not confirmed at sensitivity analysis. This meta-analysis of the best available evidence (Level 2a) demonstrated that DLT and DDLT have comparable outcomes. As indications for liver transplantation expand, future high-quality research is encouraged to increase the DLT numbers in clinical practice, serving the growing waiting list candidates, with the caveat of uncertain de novo disease transmission risks.

Domino liver transplantation for maple syrup urine disease in children: A single-center case series.

Domino liver transplant (DLT) represents another type of liver donor to expand the donor pool. Recent reports of successful DLT in children with maple syrup urine disease (MSUD) show promising long-term outcomes. It was a retrospective study. All children with MSUD were paired with either recipients with end-stage liver disease (ESLD) or non-MSUD metabolic disease. Each pair underwent simultaneous liver transplant (LT), where the MSUD recipient received the graft from a living-related donor and the liver explanted from the MSUD donor was transplanted to the respective paired domino recipient. We report our experience regarding the techniques and outcomes of DLT at our center. Eleven children with MSUD and 12 respective DLT recipients were enrolled, one of which was domino split-liver transplantation. DLT recipients included seven ESLD, two propionic acidemia (PA), one glycogen storage disease(GSD) type-1, one GSD type-3, and one Citrullinemia. Post-LT ICU and hospital stays were comparable (p > .05). Patient and graft survival was 100% and 66.6% in the MSUD group and DLT recipients at a mean follow-up of 13.5 and 15 months. There was no death in the MSUD group as compared to four in the DLT group. The amino acid levels rapidly normalized after the LT in the children with MSUD and they tolerated the normal unrestricted diet. No vascular, biliary, or graft-related complications were seen in the post-transplant period. No occurrence of MSUD was noted in DLT recipients. DLTs have excellent post-surgical outcomes. DLT should be strongly considered and adopted by transplant programs worldwide to circumvent organ shortage.

Domino Liver Transplantation for Unresectable Colon Cancer Liver Metastasis From a Donor With Heterozygous Familial Hyperlipidemia: A Case Report

Liver transplantation (LT) is a potential curative treatment for unresectable colorectal cancer liver metastasis (CRLM). Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels. Liver transplantation is offered for selected cases, and an explanted liver can be used as a domino graft. We report the first report of domino LT for unresectable CRLM using a liver from a patient with heterozygous FH. The domino donor was a 30-year-old female with a history of heterozygous FH. She had failed medical therapies for FH, including plasmapheresis; therefore, she underwent living donor LT as a treatment for FH. The explanted liver was transplanted to the domino recipient. She has been doing well with normal LDL-C levels. The domino recipient was a 44-year-old female with a history of stage 4 sigmoid cancer with liver metastases, for which she underwent laparoscopic sigmoid colectomy and right hepatectomy. She developed unresectable lesions in the remnant left lobe, which were controlled well with chemotherapy; therefore, she underwent domino LT. She is doing well without recurrence at the 31-month follow-up. Domino LT from a donor with heterozygous FH is feasible for strictly selected patients with unresectable CRLM.

Living Donor-Initiated Domino Split-Liver Transplantation in Pediatric Setup: A Case Report With Literature Review

In patients undergoing liver transplantation for metabolic diseases, removing the patient's liver for transplantation to another recipient is called "domino liver transplantation." The extracted liver can be divided and transplanted into 2 recipients, which is called domino split-liver transplantation in the literature. However, in our study, the domino liver was obtained from a pediatric patient. A patient with maple syrup urine disease (MSUD) underwent a living donor liver transplant, and the explanted liver was divided in situ into right and left lobes and transplanted to 2 separate patients. Demographic data, surgical techniques, postoperative period, and patient follow-ups were evaluated. The father's left lobe liver graft was transplanted into a 12-year-old boy with MSUD. The removed liver was divided in situ into right and left lobes. The left lobe was transplanted to a 14-year-old male patient, whereas the right lobe was transplanted to a 67-year-old male patient. The donor and the first recipient were discharged on postoperative days 5 and 22. The second pediatric patient who underwent domino split-left lobe transplantation was discharged on postoperative day 23. The adult patient who underwent domino split-right lobe transplantation died on postoperative day 12 owing to massive esophageal variceal bleeding. Patients who underwent liver transplantation due to MSUD are among the best donor choices for domino liver transplantation. If the extracted liver has a sufficient volume and anatomic features for a split, it can be used in "selected cases."

Ocular findings in patients with acquired ATTRv amyloidosis following domino liver transplantation.

To investigate the presence of amyloidosis-related ocular findings in patients who received domino liver transplantation from ATTRv amyloidosis donors. We reviewed the ocular findings in patients who had previously undergone domino liver transplantation and received ophthalmologic examinations between January 2009 and March 2023. The presence of amyloidosis-related ocular findings was retrospectively assessed by two ophthalmologists. During the study period, a total of 7 patients with 14 eyes were examined. All patients were considered as acquired ATTRv amyloidosis. The mean age at the final visit was 64.6±8.4 years (52-75 years), and the mean time since domino liver transplantation was 167.6±76.2 months (69-257 months). The two evaluators' assessments for amyloidosis-related ocular findings were completely identical. No amyloid fibril deposition was observed in the pupil, lens, or vitreous. Five patients (10 eyes) had a Schirmer test result of 5mm or less than 5 mm, and four patients with a total of 8 eyes underwent fluorescein angiography and indocyanine green angiography, and no evidence of retinal amyloid angiopathy was found on fluorescein angiography. However, three patients with 6 eyes showed choroidal amyloid angiopathy on indocyanine green angiography. While cases of choroidal amyloid angiopathy were observed, serious amyloidosis-related ocular complications such as vitreous opacity or secondary glaucoma did not occur even in the long term after domino liver transplantation.

Domino liver transplantation for adult recipients in the United States: A survival analysis

Background: Domino liver transplantation (DLT) represents a unique way to increase the availability of donor organs with explanted livers most commonly from patients with metabolic disorders.

Treatment of acquired transthyretin amyloidosis in domino liver transplantation.

Domino liver transplantation (DLT) has been commonly used during the last two decades to partly meet the high need for liver transplants. However, the recipients of grafts from patients with noncirrhotic inherited metabolic disorders may ultimately develop metabolic syndrome, and management is usually intricate, being complicated by the underlying initial disorder, other comorbidities, and post-transplantation conditions. We report here the management and the outcome in a patient with acquired transthyretin amyloidosis after DLT and significant comorbidities. Final treatment with a transthyretin gene silencing agent, patisiran, was well tolerated and resulted in remission of the aggravating neurological deficits in a follow-up period of 2 years. The case presented here supports the concept that patisiran can target the hepatocytes producing the mutated transthyretin in acquired transthyretin amyloidosis, as efficiently as in hereditary transthyretin amyloidosis (hATTR), and can be used to treat patients with transthyretin amyloidosis after DLT.

Domino liver transplantation: Expanding the liver donor pool to the pediatric recipient.

Domino liver transplantation: Expanding the liver donor pool to the pediatric recipient.

Domino liver transplants: where do we stand after a quarter-century? A US national analysis.

Domino liver transplantation (DLT) utilizes a phenotypically normal explant from select recipients as a donor graft in another patient. The procedure is not widely employed and remains restricted to a small number of centers. The purpose of this study was to assess the national profile of DLT in the United States (US) and evaluate current survival outcomes. The United Network for Organ Sharing (UNOS) database was queried for all liver transplants (LT) between 1996 and 2020. Outcomes of interest were long-term graft and patient survival. Of 181,976 LTs performed nationally during the study period, 185 (0.1%) were DLTs. Amyloidosis and maple syrup urine disease (MSUD) accounted for 83% of dominoed allografts. Out of 210 explants with amyloidosis, 103 (49%) were dominoed into secondary recipients. Only 50 (22%) of all MSUD explants (n=227) were dominoed. Graft survival was 79%, 73% and 53% at 3-, 5- and 10-years, respectively, for DLT recipients. Overall patient survival was 83%, 76% and 57% at 3-, 5- and 10-years. Despite excellent long-term survival outcomes, DLT allografts comprise a very small percentage of the liver donor pool. A large proportion of potential DLTs may be unconscionably excluded despite shortages in deceased donor organs.

Prognostic Factors Evaluation for Liver Transplant Mismatching: A New Way of Selecting and Allocating Organs

Liver transplant (LT) is the standard therapy for end-stage liver disease. Advances in surgical techniques and immunosuppression protocols improved the results of LT by increasing long-term survival. Nevertheless, an adequate match between the donor and recipient is paramount for avoiding futile liver transplants. We aimed to identify the prognostic factors in donor-recipient LT matching. Retrospective analysis of adult LT was conducted from January 2006 to December 2018, which included the following transplant modalities: deceased donor LT (DDLT), living donor LT (LDLT), combined liver-kidney transplant (CLKT), and domino LT (DLT). Among 1101 patients who underwent LT, 958 patients underwent DDLT, 92 patients underwent LDLT, 45 patients underwent CLKT, and 6 patients underwent DLT. The overall survival (OS) in 1, 5, and 10 years were 89%, 83%, and 82%, respectively. For DDLT, OS in 1, 5, and 10 years were 91%, 84%, and 82%, respectively. For LDLT, OS in 1, 5, and 10 years were 89%, 72%, and 69%, respectively. For CKLT, OS in 1, 5, and 10 years were 90%, 71%, and 71%, respectively. None of the DLT patients died. For DDLT, the factors that affected OS were the presence of fulminant liver failure (odds ratio [OR], 2.23; 95% CI, 1.18-4.18; P=.001), hemodialysis before LT (OR, 2.12; 95% CI, 1.27-3.5; P=.004), retransplant (OR, 4.74; 95% CI, 2.75-8.17; P=.000), and recipient age >60 years (OR, 1.86; 95% CI, 1.27-2.73; P=.001). For hospitalization before LT (due to an acute-on-chronic liver failure), the OR was 2.10 (95% CI, 1.29-3.42; P=.003). Donor intensive care unit time >7 days (OR, 1.46; 95% CI, 1.04-2.06; P=.02) was also associated with overall mortality. We identified prognostic factors in donor-recipient LT matching. Furthermore, we demonstrated that an adequate organ allocation with donor-recipient selection might increase graft survival and reduce waiting list mortality.

Treatment With Diflunisal in Domino Liver Transplant Recipients With Acquired Amyloid Neuropathy.

Objectives: To analyze the efficacy and tolerability of diflunisal for the treatment of acquired amyloid neuropathy in domino liver transplant recipients. Methods: We performed a retrospective longitudinal study of prospectively collected data for all domino liver transplant recipients with acquired amyloid neuropathy who received diflunisal at our hospital. Neurological deterioration was defined as an score increase of ≥2 points from baseline on the Neurological Impairment Scale/Neurological Impairment Scale-Lower Limbs. Results: Twelve patients who had received compassionate use treatment with diflunisal were identified, of whom seven had follow-up data for ≥12 months. Five patients (71.4%) presented with neurological deterioration on the Neurological Impairment Scale after 12 months (p = 0.0382). The main adverse effects were cardiovascular and renal, leading to diflunisal being stopped in five patients and the dose being reduced in two patients. Conclusion: Our study suggests that most domino liver transplant recipients with acquired amyloid neuropathy will develop neurological deterioration by 12 months of treatment with diflunisal. This therapy was also associated with a high incidence of adverse effects and low treatment retention. The low efficacy and low tolerability of diflunisal treatment encourage the search for new therapeutic options.

Surgical Outcomes of Domino Liver Transplantation Using Grafts From Living Donors With Familial Amyloid Polyneuropathy.

Domino liver transplantation (DLT) using grafts from donors with familial amyloid polyneuropathy is an acceptable procedure for expanding the donor pool. The vascular and biliary reconstructions in living donor DLT (LDDLT) are technically demanding, and data on the short-term and long-term surgical outcomes of domino donors and recipients in LDDLT are limited. In this study, we identified 25 domino recipients from our liver transplantation program (1999-2018), analyzed the vascular and biliary reconstructions performed, and evaluated the surgical outcomes, including graft survival. Piggyback technique was adopted in all 25 domino donors. The only surgical complication in domino donors was hepatic vein (HV) stenosis with an incidence rate of 4%. In 22 domino recipients, right HV and middle/left HV were reconstructed separately. A total of 10 recipients had 2 arteries anastomosed, and 18 underwent duct-to-duct biliary anastomosis. HV stenosis and biliary stricture had incidence rates of 8% and 24%, respectively, in the recipients, but none of them developed hepatic artery thrombosis. The 1-year and 5-year graft survival rates were 100% each in the domino donors, and 84.0% and 67.3% in the domino recipients, respectively. In conclusion, LDDLT has acceptable outcomes without increasing the operative risk in donors despite the demanding surgical technique involved.

Domino Liver Transplants: after a Quarter of a Century are We Still Wasting Too Many Usable Grafts?

Introduction: Domino liver transplantation (DLT) has emerged as a rational approach to help organ shortage concerns. but remains restricted to a small number of centers. The purpose of this study was to assess the national profile of DLT in the United States and evaluate current donor and recipient outcomes. Methods: National data from 1987 - 2020 was extracted from the United Network for Organ Sharing (UNOS) database. Analyses included all pediatric and adult donors and recipients of DLT during this study period. Results: A total of 181,976 liver transplants were performed in the US between 1987 and 2020 of which 185 were DLTs (0.1%) performed in 42 centers. The median (IQR) donor and recipient wait-times for transplantation were 180 (85 –413) and 213 (81 –525) days, respectively. Since 1996, amyloidosis accounted for 210 of all LTs and 103 (49%) of DLTs. Of the 227 patients receiving LT for maple syrup urine disease (MSUD), 50 (22%) were used for DLT. Thirty-two patients with homozygous familial hypercholesterolemia received a standard LT and 4 (14%) were DLT allografts. Recipient DLT graft survival was 91%, 79% and 73% at 1-, 3- and 5-years with an overall survival of 93%, 83% and 76%. Conclusion: Accounting for only 0.1% of all liver transplants to date, DLT has yet to be fully embraced by US programs. A small proportion of explants with amyloidosis and MSUD may be wrongly discarded. Despite this caveat, domino recipients showed excellent survival outcomes postoperatively that appear comparable to standard liver transplantation approaches.

Outcomes of Pediatric Liver Transplantation in Japan: A Report from the Registry of the Japanese Liver Transplantation Society.

The Japanese Liver Transplantation Society (JLTS), a cooperative research consortium, was established in 1980 to characterize and follow trends in patient characteristics and graft survival among all liver transplant patients in Japan. This study analyzed factors that may affect the current outcomes of pediatric patients who undergo liver transplantation (LT) by evaluating one of the largest pediatric LT cohorts in the world. Between November 1989 and December 2018, 3347 pediatric patients underwent LT in Japan. The survival outcomes of each donor and recipient variant were evaluated. The procedures performed during the study period included living donor LT (LDLT; n = 3271), deceased donor LT (DDLT; n = 69), and domino LT (n = 7). There were 1510 male (45.1%) and 1837 female (54.9%) recipients with a median age of 1.7 y (range: 9 d to 17.9 y). The graft survival rates at 1, 10, 20, and 30 y were 88.9%, 82.2%, 77.1%, and 75.4%, respectively. Donor age, donor BMI, blood type incompatibility, recipient age, etiology of liver disease, transplant type, center experience, and transplant era were found to be significant predictors of overall graft survival. LDLT is a major treatment modality for the end-stage liver disease in children; DDLT and domino LT were applied as alternative treatments for LDLT in patients with specific pediatric liver diseases that are considered to have a poor prognosis following LDLT. Satisfactory long-term pediatric patient survival outcomes were achieved in the JLTS series, and we should continue to promote the deceased donor organ transplantation program in Japan.