Development of an organ failure score in acute liver failure for transplant selection and identification of patients at high risk of futility.

INTRODUCTION: King's College Hospital criteria are currently used to select liver transplant candidates in acetaminophen-related acute liver failure (ALF). Although widely accepted, they show a poor sensitivity in predicting pre-transplant mortality and cannot predict the outcome after surgery. In this study we aimed to develop a new prognostic score that can allow patient selection for liver transplantation more appropriately and identify patients at high risk of futile transplantation. METHODS: We analysed consecutive patients admitted to the Royal Free and Beaujon Hospitals between 1990 and 2015. Clinical and laboratory data at admission were collected. Predictors of 3-month mortality in the non-transplanted patients admitted to the Royal Free Hospital were used to develop the new score, which was then validated against the Beaujon cohort. The Beaujon-transplanted group was also used to assess the ability of the new score in identifying patients at high risk of transplant futility. RESULTS: 152 patients were included of who 44 were transplanted. SOFA, CLIF-C OF and CLIF-ACLF scores were the best predictors of 3-month mortality among non-transplanted patients. CLIF-C OF score and high dosages of norepinephrine requirement were the only significant predictors of 3-month mortality in the non-transplanted patients, and therefore were included in the ALF-OFs score. In non-transplanted patients, ALF-OFs showed good performance in both exploratory (AUC = 0.89; sensitivity = 82.6%; specificity = 89.5%) and the validation cohort (AUC = 0.988; sensitivity = 100%; specificity = 92.3%). ALF-OFs score was also able to identify patients at high risk of transplant futility (AUC = 0.917; sensitivity = 100%; specificity = 79.2%). CONCLUSION: ALF-OFs is a new prognostic score in acetaminophen-related ALF that can predict both the need for liver transplant and high risk of transplant futility, improving candidate selection for liver transplantation

Multimodal therapy including yttrium-90 radioembolization as a bridging therapy to liver transplantation for a huge and locally advanced intrahepatic cholangiocarcinoma

International audienceTreatment of intrahepatic cholangiocarcinoma remains a major challenge. For an unresectable lesion without extrahepatic spread, liver transplantation could be a potential solution but it is still associated with poor oncologic results owing to the absence of effective neoadjuvant treatment. We report the case of a young man with locally advanced intrahepatic cholangiocarcinoma presenting with multiple intrahepatic metastases and vascular structure involvement. The lesion was significantly downstaged by a multimodal therapy including intra-arterial Yttrium-90 radioembolization, systemic chemotherapy and external radiotherapy, allowing liver transplantation. Three years after the procedure, oncologic outcome is excellent with no sign of recurrence. Multimodal therapy including Yttrium-90 radioembolization could be relevant as neoadjuvant treatment before liver transplantation for unresectable intrahepatic cholangiocarcinoma. © 2016, Romanian Society of Gastroenterology. All rights reserved

High intrapatient variability of tacrolimus exposure is associated with poorer outcomes after liver transplantation

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Guide pratique de suivi du transplanté hépatique

International audienceSi l’amélioration des techniques chirurgicales et l’immunosuppresison ont permis le développement avec succès de la transplantation d’organe solide, les complications médicales au long cours persistent et sont responsables d’un déclin de la survie dès la première année après la greffe. Les complications liées au greffon (rejet, récidive de la maladie initiale, thrombose vasculaire), tumorales (cancer de novo ou récidive), cardiovasculaires, infectieuses et rénales sont les principales causes de décès après transplantation hépatique. La prévention, le diagnostic et le management de ces complications restent un véritable défi pour tout praticien prenant en charge ces patients. Une meilleure gestion des facteurs tels que le diabète, la dyslipidémie, l’hypertension artérielle et l’insuffisance rénale, peut avoir une incidence sur la mortalité à long terme. Un suivi standardisé associé à un dépistage organisé des complications médicales et chirurgicales sont donc indispensables afin d’adapter précocement la prise en charge et ainsi améliorer la survie après la greffe

A high performance liquid chromatography tandem mass spectrometry for the quantification of tacrolimus in human bile in liver transplant recipients

International audienceTacrolimus whole-blood concentrations imperfectly reflect concentrations at the effect site. Tacrolimus concentrations in the transplanted organ could be more relevant to predict rejection events. Because liver biopsy cannot be repeatedly performed after liver transplantation, we suggested measuring tacrolimus in the bile to have a cost-effective and clinically implementable surrogate marker of intra-hepatic tacrolimus concentration. We developed and fully validated a liquid chromatography–tandem mass spectrometry method for the determination of tacrolimus in human bile. Sample purification was achieved using protein precipitation and liquid–liquid extraction with ethyl-acetate. Gradient elution was performed using a C18 analytical column with a 5 min run-time. The method was linear from 0.5 ng/mL to 20 ng/mL. In this concentration range, within-day and between-day precisions as well as overall bias were within ±15%. Matrix effect was fully corrected by the internal standard (ascomycin). The assay was optimized to achieve good selectivity in this complex biological matrix. Tacrolimus was found to be stable in bile stored 6 months at −80 °C, after 3 freeze and thaw cycles, 20 h at room temperature and 24 h in extracts kept at 15 °C in the auto-sampler. The method was applied to quantify tacrolimus in bile from liver transplant recipients. It allowed getting preliminary data about tacrolimus excretion profile in bile and showed the lack of correlation between tacrolimus whole blood concentration and tacrolimus liver exposition. This alternative and innovative analytical approach of tacrolimus bio-analysis appears suitable for further studies evaluating relevance of biliary tacrolimus concentration as a new pharmacological marker of immunosuppressive activity. © 2016 Elsevier B.V

P0709 : Survival of patients infected by chronic hepatitis c and f0f1 fibrosis at baseline after a 15 years follow-up

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Nirmatrelvir/ritonavir: Efficacy, safety and drug monitoring in a real-life cohort of outpatient liver transplant recipients

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Deciphering pharmacogenetic-whole blood/intracellular pharmacokinetic-pharmacodynamic (PG-PK2-PD) relationship of tacrolimus in liver transplant recipients

International audienceMeeting Abstract PS-16

Baseline serum ferritin is an independent predictive factor of mortality in patients with chronic hepatitis C after long term follow-up

International audienceInternational Liver Congress / 52nd Annual Meeting of the European-Association-for-the-Study-of-the-Liver, Amsterdam, Netherland, April 201

P0804 : Efficacy of sofosbuvir-based treatment regimens in HIV/HCV co-infected patients after liver transplantation: The ANRS CO23 CUPILT study

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