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Prospective, single-centre, randomised controlled trial to evaluate the efficacy and safety of ischaemia-free liver transplantation (IFLT) in the treatment of end-stage liver disease.

ABSTRACT: INTRODUCTION:During conventional liver transplantation (CLT), ischaemia-reperfusion injury (IRI) is inevitable and is associated with complications such as early allograft dysfunction (EAD), primary non-function and ischaemic-type biliary lesions. We have established a novel procedure called ischaemia-free liver transplantation (IFLT). The results from a pilot study suggest that IFLT might prevent IRI and yield better transplant outcomes than CLT. The purpose of this study was to further assess the efficacy and safety of IFLT versus CLT in patients with end-stage liver disease. METHODS AND ANALYSIS:This is an investigator-initiated, open-label, phase III, prospective, single-centre randomised controlled trial on the effects of IFLT in patients with end-stage liver disease. Adult patients (aged 18-75 years) eligible for liver transplantation will be screened for participation in this trial and will be randomised between the IFLT group (n=34) and the CLT group (n=34). In the IFLT group, the donor liver will be procured, preserved and implanted with continuous normothermic machine perfusion (NMP). In the CLT group, the donor liver will be procured after a fast cold flush, preserved in 0°C-4°C?solution and implanted under hypothermic and hypoxic conditions. Patients in both groups will be managed according to the standard protocol of our centre. The primary end point is the incidence of EAD after liver transplantation. Intraoperative and postoperative parameters of donor livers and recipients will be observed and recorded, and postoperative liver graft function, complications and recipient and graft survival will be evaluated. After a 12-month follow-up of the last enrolled recipient, the outcomes will be analysed to evaluate the safety and efficacy of IFLT versus CLT in patients with end-stage liver disease. ETHICS AND DISSEMINATION:The protocol was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Sun Yat-sen University. The findings will be disseminated to the public through conference presentations and peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER:ChiCTR1900021158.

SUBMITTER: Huang C

PROVIDER: S-EPMC7223152 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Prospective, single-centre, randomised controlled trial to evaluate the efficacy and safety of ischaemia-free liver transplantation (IFLT) in the treatment of end-stage liver disease.

Huang Changjun C Huang Shanzhou S Tang Yunhua Y Zhao Qiang Q Wang Dongping D Ju Weiqiang W Yang Lu L Zhang Jian J Wu Linwei L Chen Maogen M Zhang Zhiheng Z Zhu Zebin Z Wang Linhe L Zhu Caihui C Zhang Yixi Y Sun Chengjun C Xiong Wei W Shen Yuekun Y Chen Xiaoxiang X Ma Yi Y Hu Anbin A Zhu Xiaofeng X Rong Jian J Cai Changjie C Guo Zhiyong Z He Xiaoshun X

BMJ open 20200505 5

<h4>Introduction</h4>During conventional liver transplantation (CLT), ischaemia-reperfusion injury (IRI) is inevitable and is associated with complications such as early allograft dysfunction (EAD), primary non-function and ischaemic-type biliary lesions. We have established a novel procedure called ischaemia-free liver transplantation (IFLT). The results from a pilot study suggest that IFLT might prevent IRI and yield better transplant outcomes than CLT. The purpose of this study was to further ...[more]

PMID: 32376754

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Project description:Background Ischaemia-reperfusion injury is considered an inevitable component of organ transplantation, compromising organ quality and outcomes. Although several treatments have been proposed, none has avoided graft ischaemia and its detrimental consequences. Methods Ischaemia-free liver transplantation (IFLT) comprises surgical techniques enabling continuous oxygenated blood supply to the liver of brain-dead donor during procurement, preservation, and implantation using normothermic machine perfusion technology. In this non-randomised study, 38 donor livers were transplanted using IFLT and compared to 130 conventional liver transplants (CLT). Findings Two recipients (5•3%) in the IFLT group experienced early allograft dysfunction, compared to 50•0% in patients receiving conventional transplants (absolute risk difference, 44•8%; 95% confidence interval, 33•6-55•9%). Recipients of IFLT had significantly reduced median (IQR) peak aspartate aminotransferase levels within the first week compared to CLT recipients (365, 238-697 vs 1445, 791-3244 U/L, p<0•001); likewise, median total bilirubin levels on day 7 were significantly lower (2•34, 1•39-4•09 mg/dL) in the IFLT group than in the CLT group (5•10, 1•90-11•65 mg/dL) (p<0•001). Moreover, IFLT recipients had a shorter median intensive care unit stay (1•48, 0•75-2•00 vs 1•81, 1•00-4•58 days, p=0•006). Both one-month recipient (97•4% vs 90•8%, p=0•302) and graft survival (97.4% vs 90•0%, p=0•195) were better for IFLT than CLT, albeit differences were not statistically significant. Subgroup analysis showed that the extended criteria donor livers transplanted using the IFLT technique yielded faster post-transplant recovery than did the standard criteria donor livers transplanted using the conventional approach. Interpretation IFLT provides a novel approach that may improve outcomes, and allow the successful utilisation of extended criteria livers. Funding This study was funded by National Natural Science Foundation of China, Guangdong Provincial Key Laboratory Construction Projection on Organ Donation and Transplant Immunology, and Guangdong Provincial international Cooperation Base of Science and Technology. Panel: Research in context.

Project description:BACKGROUND & AIM:The goal of organ allocation is to distribute a scarce resource equitably to the sickest patients. In the United States, the Model for End-stage Liver Disease (MELD) is used to allocate livers for transplantation. Patients with greater MELD scores are at greater risk of death on the waitlist and are prioritized for liver transplant (LT). The MELD is capped at 40 however, and patients with calculated MELD scores >40 are not prioritized despite increased mortality. We aimed to evaluate waitlist and post-transplant survival stratified by MELD to determine outcomes in patients with MELD >40. METHODS:Using United Network for Organ Sharing data, we identified patients listed for LT from February 2002 through to December 2012. Waitlist candidates with MELD ?40 were followed for 30days or until the earliest occurrence of death or transplant. RESULTS:Of 65,776 waitlisted patients, 3.3% had MELD ?40 at registration, and an additional 7.3% had MELD scores increase to ?40 after waitlist registration. A total of 30,369 (46.2%) underwent LT, of which 2,615 (8.6%) had MELD ?40 at transplant. Compared to MELD 40, the hazard ratio of death within 30days of registration was 1.4 (95% CI 1.2-1.6) for patients with MELD 41-44, 2.6 (95% CI 2.1-3.1) for MELD 45-49, and 5.0 (95% CI 4.1-6.1) for MELD ?50. There was no difference in 1- and 3-year survival for patients transplanted with MELD >40 compared to MELD=40. A survival benefit associated with LT was seen as MELD increased above 40. CONCLUSIONS:Patients with MELD >40 have significantly greater waitlist mortality but comparable post-transplant outcomes to patients with MELD=40 and, therefore, should be given priority for LT. Uncapping the MELD will allow more equitable organ distribution aligned with the principle of prioritizing patients most in need. Lay summary: In the United States (US), organs for liver transplantation are allocated by an objective scoring system called the Model for End-stage Liver Disease (MELD), which aims to prioritize the sickest patients for transplant. The greater the MELD score, the greater the mortality without liver transplant. The MELD score, however, is artificially capped at 40 and thus actually disadvantages the sickest patients with end-stage liver disease. Analysis of the data advocates uncapping the MELD score to appropriately prioritize the patients most in need of a liver transplant.

Project description:Background & aimsDespite recent attention to differences in access to livers for transplantation, research has focused on patients already on the wait list. We analyzed data from a large administrative database that represents the entire US population, and state Medicaid data, to identify factors associated with differences in access to wait lists for liver transplantation.MethodsWe performed a retrospective cohort study of transplant-eligible patients with end-stage liver disease using the HealthCore Integrated Research Database (2006-2014; n = 16,824) and Medicaid data from 5 states (2002-2009; California, Florida, New York, Ohio, and Pennsylvania; n = 67,706). Transplant-eligible patients had decompensated cirrhosis, hepatocellular carcinoma (HCC), and/or liver synthetic dysfunction, based on validated International Classification of Diseases, Ninth Revision-based algorithms and data from laboratory studies. Placement on the wait list was determined through linkage with the Organ Procurement and Transplantation Network database.ResultsIn an unadjusted analysis of the HealthCore database, we found that 29% of patients with HCC were placed on the 2-year wait list (95% confidence interval [CI], 25.4%-33.0%) compared with 11.9% of patients with stage 4 cirrhosis (ascites) (95% CI, 11.0%-12.9%) and 12.6% of patients with stage 5 cirrhosis (ascites and variceal bleeding) (95% CI, 9.4%-15.2%). Among patients with each stage of cirrhosis, those with HCC were significantly more likely to be placed on the wait list; adjusted subhazard ratios ranged from 1.7 (for patients with stage 5 cirrhosis and HCC vs those without HCC) to 5.8 (for patients with stage 1 cirrhosis with HCC vs those without HCC). Medicaid beneficiaries with HCC were also more likely to be placed on the transplant wait list, compared with patients with decompensated cirrhosis, with a subhazard ratio of 2.34 (95% CI, 2.20-2.49). Local organ supply and wait list level demand were not associated with placement on the wait list.ConclusionsIn an analysis of US healthcare databases, we found patients with HCC to be more likely to be placed on liver transplant wait lists than patients with decompensated cirrhosis. Previously reported reductions in access to transplant care for wait-listed patients with decompensated cirrhosis underestimate the magnitude of this difference.

Dataset Information

Prospective, single-centre, randomised controlled trial to evaluate the efficacy and safety of ischaemia-free liver transplantation (IFLT) in the treatment of end-stage liver disease.

Publications

Prospective, single-centre, randomised controlled trial to evaluate the efficacy and safety of ischaemia-free liver transplantation (IFLT) in the treatment of end-stage liver disease.

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