Long-term outcomes after hypothermic oxygenated machine perfusion and transplantation of 1,202 donor livers in a real-world setting (HOPE-REAL study).

BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

Development of a genomic predictive model for cholangiocarcinoma using copy number alteration data.

AIMS: Cholangiocarcinoma (CC) is a rare tumour arising from the biliary tract epithelium. The aim of this study was to perform a genomic characterisation of CC tumours and to implement a model to differentiate extrahepatic (ECC) and intrahepatic (ICC) cholangiocarcinoma. METHODS: DNA extracted from tumour samples of 23 patients with CC, namely 10 patients with ECC and 13 patients with ICC, was analysed by array comparative genomic hybridisation. A support vector machine algorithm for classification was applied to the genomic data to distinguish between ICC and ECC. A survival analysis comparing both groups of patients was also performed. RESULTS: With these whole genome results, we observed several common alterations between tumour samples of the same CC anatomical type, namely gain of Xp and loss of 3p, 11q11, 14q, 16q, Yp and Yq in ICC tumours, and gain of 16p25.3 and loss of 3q26.1, 6p25.3-22.3, 12p13.31, 17p, 18q and Yp in ECC tumours. Gain of 2q37.3 was observed in the samples of both tumour subtypes, ICC and ECC. The developed genomic model comprised four chromosomal regions that seem to enable the distinction between ICC and ECC, with an accuracy of 71.43% (95% CI 43% to 100%). Survival analysis revealed that in our cohort, patients with ECC survived on average 8 months less than patients with ICC. CONCLUSIONS: This genomic characterisation and the introduction of genomic models to clinical practice could be important for patient management and for the development of targeted therapies. The power of this genomic model should be evaluated in other CC populations.

Auxiliary Liver Transplantation as a Transient Treatment for Acute Liver Failure: Two Cases.

INTRODUCTION: Acute liver failure is an uncommon condition associated with a high mortality. Most patients do not survive without liver transplantation. In the last decades, auxiliary liver transplantation has emerged as a therapeutic option. CLINICAL CASE: The authors present two cases of acute liver failure that required liver transplantation. Given the patients' young age and the preserved macroscopic liver pattern evaluated in surgery, auxiliary liver transplantation was executed using different surgical approaches. Afterwards, following confirmed full native liver regeneration, the patients were submitted to auxiliary liver hepatectomy, which was accomplished without complications. CONCLUSION: Auxiliary liver transplantation can be regarded as an effective temporary treatment for acute liver failure in selected cases, allowing an immunosuppression-free life.

INTRODUÇÃO: A falência hepática aguda é uma entidade clínica pouco comum, mas associada a elevada mortalidade. A maioria dos doentes não sobreviverá sem transplante hepático. Nas últimas décadas, o transplante hepático auxiliar tem sido utilizado como uma opção terapêutica valorizável. CASO CLÍNICO: Apresentam-se dois casos de falência hepática aguda tratados com transplante hepático. Tendo em conta a idade jovem dos doentes e a noção de preservação macroscópica do fígado, recorreu-se à opção de transplante hepático auxiliar utilizando técnicas diferentes. Posteriormente, após confirmação de regeneração hepática completa, procedeu-se à hepatectomia do fígado auxiliar. CONCLUSÃO: O transplante hepático auxiliar constitui uma terapêutica transitória eficaz em alguns casos de falência hepática aguda, permitindo um futuro isento de imunossupressão.