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1.
J Hepatol ; 78(5): 1007-1016, 2023 05.
Article in English | MEDLINE | ID: mdl-36740047

ABSTRACT

BACKGROUND & AIMS: Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially enable the assessment of livers before use. METHODS: Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, the UK, and the US. Initial type-III DCD liver offers were correlated with accepted, recovered and implanted livers. RESULTS: A total number of 34,269 DCD livers were offered, resulting in 9,780 liver transplants (28.5%). The discard rates were highest in the UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g. between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, we observed large differences in the use of various machine perfusion techniques, as well as in graft and donor risk factors. For example, the median donor age and functional donor warm ischemia time were highest in Italy, e.g. >40 min, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in 5-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS: Overall, DCD liver discard rates across the eight countries were high, although this primarily reflects the situation in the Netherlands, the UK and the US. Countries where in situ and ex situ machine perfusion strategies were used routinely had better DCD utilization rates without compromised outcomes. IMPACT AND IMPLICATIONS: A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5% but varies significantly between 18.9% and 74.2%. For example, the median DCD-III liver utilization in five countries, e.g. Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, 1- and 5-year graft survival rates remain fairly similar among all participating countries. A highly varying experience with modern machine perfusion technology was observed. In situ and ex situ liver perfusion concepts, and application of assessment tools for type-III DCD livers before transplantation, may be a key explanation for the observed differences in DCD-III utilization.


Subject(s)
Cardiovascular System , Liver Transplantation , Tissue and Organ Procurement , Humans , Liver , Tissue Donors , Liver Transplantation/methods , Graft Survival , Organ Preservation/methods , Perfusion/methods
2.
Pediatr Nephrol ; 38(8): 2887-2896, 2023 08.
Article in English | MEDLINE | ID: mdl-36840752

ABSTRACT

BACKGROUND: As modern medicine is advancing, younger, small, and more complex children are becoming multi-organ transplant candidates. This brings up new challenges in all aspects of their care. METHODS: We describe the first report of a small child receiving a simultaneous liver and kidney transplant and abdominal rectus sheath fascia transplant on the background of Williams syndrome and methylmalonic acidaemia. At the time of transplantation, the child was 3 years old, weighed 14.0 kg, had chronic kidney disease stage V, and had not yet started any other form of kidney replacement therapy. RESULTS: There were many anaesthetic, medical, metabolic, and surgical challenges to consider in this case. A long general anaesthetic time increased the risk of cardiac complications and metabolic decompensation. Additionally, the small size of the patient and the organ size mis-match meant that primary abdominal closure was not possible. The patient's recovery was further complicated by sepsis, transient CNI toxicity, and de novo DSAs. CONCLUSIONS: Through a multidisciplinary approach between 9 specialties in 4 hospitals across England and Wales, and detailed pre-operative planning, a good outcome was achieved for this child. An hour by hour management protocol was drafted to facilitate transplant and included five domains: 1. management at the time of organ offer; 2. before the admission; 3. at admission and before theatre time; 4. intra-operative management; and 5. post-operative management in the first 24 h. Importantly, gaining a clear and in depth understanding of the metabolic state of the patient pre- and peri-operatively was crucial in avoiding metabolic decompensation. Furthermore, an abdominal rectus sheath fascia transplant was required to achieve abdominal closure, which to our knowledge, had never been done before for this indication. Using our experience of this complex case, as well as our experience in transplanting other children with MMA, and through a literature review, we propose a new perioperative management pathway for this complex cohort of transplant recipients.


Subject(s)
Amino Acid Metabolism, Inborn Errors , Kidney Failure, Chronic , Kidney Transplantation , Liver Transplantation , Child , Humans , Child, Preschool , Liver Transplantation/adverse effects , Liver Transplantation/methods , Amino Acid Metabolism, Inborn Errors/complications , Kidney Failure, Chronic/complications , Liver , Kidney Transplantation/adverse effects , Kidney Transplantation/methods
4.
HPB (Oxford) ; 24(5): 596-605, 2022 05.
Article in English | MEDLINE | ID: mdl-34702624

ABSTRACT

BACKGROUND: The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score as a prognostic index for recurrence has been reported previously and has not been validated outside the USA. Our study has validated the score in a single center UK cohort of patients being transplanted for HCC. METHODS: LT for HCC between 2008 and 2018 at our center were analyzed. Recurrence-free survival (RFS) was compared by the RETREAT score and validated using Net Reclassification Improvement (NRI) by comparing it to Milan criteria. RESULTS: 346 adult HCC patients were transplanted of whom 313 were included. 28 (8.9%) had a recurrence. Summation of largest diameter and total number of viable tumors (HR = 1.19, p < 0.001), micro-/macro-vascular invasion (HR = 3.74, p = 0.002) and AFP>20 ng/ml (HR = 3.03, p = 0.005) were associated with recurrence on multivariate analysis. RFS decreased with increasing RETREAT score (log-rank p = 0.016). RETREAT performed better than Milan with significant NRI at 1- and 2-years post-transplant (0.43 (p = 0.004) and 0.38 (p = 0.03) respectively). CONCLUSION: LT outcomes using the revised UK criteria are equivalent to Milan criteria. Further, RETREAT score was validated as a prognostic index for the first time in a UK cohort and may assist risk stratification, selection for adjuvant therapies and guide surveillance.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Adult , Humans , Liver Transplantation/adverse effects , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies , Risk Factors , United Kingdom , alpha-Fetoproteins
5.
J Clin Med ; 10(21)2021 Oct 26.
Article in English | MEDLINE | ID: mdl-34768489

ABSTRACT

BACKGROUND: Biliary atresia (BA) is the most common indicator for liver transplant (LT) in children, however, approximately 22% will reach adulthood with their native liver, and of these, half will require transplantation later in life. The aim of this study was to analyse the surgical challenges and outcomes of patients with BA undergoing LT in adulthood. METHODS: Patients with BA requiring LT at the age of 16 or older in our unit between 1989 and 2020 were included. Pretransplant, perioperative variables and outcomes were analysed. Pretransplant imaging was reviewed to assess liver appearance, spontaneous visceral portosystemic shunting (SPSS), splenomegaly, splenic artery (SA) size, and aneurysms. RESULTS: Thirty-four patients who underwent LT for BA fulfilled the inclusion criteria, at a median age of 24 years. The main indicators for LT were synthetic failure and recurrent cholangitis. In total, 57.6% had significant enlargement of the SA, 21% had multiple SA aneurysm, and SPSS was present in 72.7% of the patients. Graft and patient survival at 1, 5, and 10 years was 97.1%, 91.2%, 91.2% and 100%, 94%, 94%, respectively Conclusions: Good outcomes after LT for BA in young patients can be achieved with careful donor selection and surgery to minimise the risk of complications. Identification of anatomical variants and shunting are helpful in guiding attitude at the time of transplant.

6.
Transplantation ; 105(6): 1156-1164, 2021 06 01.
Article in English | MEDLINE | ID: mdl-34048418

ABSTRACT

Donation after circulatory death (DCD) grafts are commonly used in liver transplantation. Attributable to the additional ischemic event during the donor warm ischemia time (DWIT), DCD grafts carry an increased risk for severe ischemia/reperfusion injury and postoperative complications, such as ischemic cholangiopathy. The actual ischemia during DWIT depends on the course of vital parameters after withdrawal of life support and varies widely between donors. The ischemic period (functional DWIT) starts when either Spo2 or blood pressure drop below a certain point and lasts until the start of cold perfusion during organ retrieval. Over the years, multiple definitions and thresholds of functional DWIT duration have been used. The International Liver Transplantation Society organized a Consensus Conference on DCD, Liver Preservation, and Machine Perfusion on January 31, 2020 in Venice, Italy. The aim of this conference was to reach consensus about various aspects of DCD liver transplantation in context of currently available evidence. Here we present the recommendations with regards to the definitions used for DWIT and functional DWIT, the importance of vital parameters after withdrawal of life support, and acceptable thresholds of duration of functional DWIT to proceed with liver transplantation.


Subject(s)
Hepatectomy , Liver Transplantation , Organ Preservation/instrumentation , Perfusion/instrumentation , Tissue Donors , Tissue and Organ Harvesting , Warm Ischemia/instrumentation , Hepatectomy/adverse effects , Humans , Liver Transplantation/adverse effects , Organ Preservation/adverse effects , Perfusion/adverse effects , Time Factors , Tissue Survival , Tissue and Organ Harvesting/adverse effects , Warm Ischemia/adverse effects
7.
N Engl J Med ; 384(15): 1391-1401, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33626248

ABSTRACT

BACKGROUND: Transplantation of livers obtained from donors after circulatory death is associated with an increased risk of nonanastomotic biliary strictures. Hypothermic oxygenated machine perfusion of livers may reduce the incidence of biliary complications, but data from prospective, controlled studies are limited. METHODS: In this multicenter, controlled trial, we randomly assigned patients who were undergoing transplantation of a liver obtained from a donor after circulatory death to receive that liver either after hypothermic oxygenated machine perfusion (machine-perfusion group) or after conventional static cold storage alone (control group). The primary end point was the incidence of nonanastomotic biliary strictures within 6 months after transplantation. Secondary end points included other graft-related and general complications. RESULTS: A total of 160 patients were enrolled, of whom 78 received a machine-perfused liver and 78 received a liver after static cold storage only (4 patients did not receive a liver in this trial). Nonanastomotic biliary strictures occurred in 6% of the patients in the machine-perfusion group and in 18% of those in the control group (risk ratio, 0.36; 95% confidence interval [CI], 0.14 to 0.94; P = 0.03). Postreperfusion syndrome occurred in 12% of the recipients of a machine-perfused liver and in 27% of those in the control group (risk ratio, 0.43; 95% CI, 0.20 to 0.91). Early allograft dysfunction occurred in 26% of the machine-perfused livers, as compared with 40% of control livers (risk ratio, 0.61; 95% CI, 0.39 to 0.96). The cumulative number of treatments for nonanastomotic biliary strictures was lower by a factor of almost 4 after machine perfusion, as compared with control. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Hypothermic oxygenated machine perfusion led to a lower risk of nonanastomotic biliary strictures following the transplantation of livers obtained from donors after circulatory death than conventional static cold storage. (Funded by Fonds NutsOhra; DHOPE-DCD ClinicalTrials.gov number, NCT02584283.).


Subject(s)
Biliary Tract/pathology , Cold Ischemia , Liver Transplantation , Organ Preservation/methods , Adult , Cold Temperature , Constriction, Pathologic/prevention & control , Female , Humans , Male , Middle Aged , Perfusion , Reperfusion Injury/prevention & control
8.
Liver Transpl ; 25(10): 1561-1570, 2019 10.
Article in English | MEDLINE | ID: mdl-31379050

ABSTRACT

Liver transplantation (LT) for small infants remains challenging because of the demands related to graft selection, surgical technique, and perioperative management. The aim of this study was to evaluate the short-term and longterm outcomes of LT regarding vascular/biliary complications, renal function, growth, and patient/graft survival in infants ≤3 months compared with those of an age between >3 and 6 months at a single transplant center. A total of 64 infants ≤6 months underwent LT and were divided into 2 groups according to age at LT: those of age ≤3 months (range, 6-118 days; XS group, n = 37) and those of age >3 to ≤6 months (range, 124-179 days; S group, n = 27) between 1989 and 2014. Acute liver failure was the main indication for LT in the XS group (n = 31, 84%) versus S (n = 7, 26%). The overall incidence of hepatic artery thrombosis and portal vein thrombosis/stricture were 5.4% and 10.8% in the XS group and 7.4% and 11.1% in the S group, respectively (not significant). The overall incidence of biliary stricture and leakage were 5.4% and 2.7% in the XS group and 3.7% and 3.7% in the S group, respectively (not significant). There was no significant difference between the 2 groups in terms of renal function. No significant difference was found between the 2 groups for each year after LT in terms of height and weight z score. The 1-, 5-, and 10-year patient survival rates were 70.3%, 70.3%, and 70.3% in the XS group compared with 92.6%, 88.9%, and 88.9% in the S group, respectively (not significant). In conclusion, LT for smaller infants has acceptable outcomes despite the challenges of surgical technique, including vascular reconstruction and graft preparation, and perioperative management.


Subject(s)
Graft Survival , Liver Failure, Acute/surgery , Liver Transplantation/adverse effects , Postoperative Complications/epidemiology , Age Factors , Female , Humans , Incidence , Infant , Liver Failure, Acute/mortality , Male , Postoperative Complications/etiology , Prospective Studies , Survival Rate , Treatment Outcome
9.
Pediatr Transplant ; 23(5): e13473, 2019 08.
Article in English | MEDLINE | ID: mdl-31124589

ABSTRACT

Primary abdominal wall closure after intestinal and multivisceral transplantation may not be possible because of loss of abdominal domain and/or graft size/abdominal cavity mismatch. Traditional closure techniques for the open abdomen may not be valid in these circumstances because of severe scarring of the abdominal wall from multiple previous surgeries in this particular group of patients. We present our initial experience with the use of non-vascularized abdominal rectus muscle fascia in two patients who underwent deceased donation and living-related combined liver and small bowel transplantation, respectively, and who could not be closed primarily. The donor fascia was attached to the recipient fascia in both patients. In either case, there was not enough skin cover for closure, the wound was left open, and a negative pressure dressing was applied. In both cases, over a period of 6 months after placement of the non-vascularized abdominal rectus muscle fascia, the wound contracted, granulation tissue gradually covered the wound, and healing occurred, giving an intact abdominal wall. The abdominal rectus muscle fascia from a deceased donor can be used in a definite procedure for closure of the abdominal wall either at the time of transplant or later when a suitable rectus muscle fascia graft becomes available.


Subject(s)
Abdominal Wall/surgery , Fasciotomy , Intestines/transplantation , Wound Closure Techniques , Child , Female , Humans , Male
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