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Holdaas H.,University of Oslo | Potena L.,University of Bologna | Saliba F.,Center Hepato Biliaire
Transplantation Reviews | Year: 2015

Post-transplant dyslipidemia is exacerbated by mammalian target of rapamycin (mTOR) inhibitors. Early clinical trials of mTOR inhibitors used fixed dosing with no concomitant reduction in calcineurin inhibitor (CNI) exposure, leading to concerns when consistent and marked dyslipidemia was observed. With use of modern concentration-controlled mTOR inhibitor regimens within CNI-free or reduced-exposure CNI regimens, however, the dyslipidemic effect persists but is less pronounced. Typically, total cholesterol levels are at the upper end of normal, or indicate borderline risk, in kidney and liver transplant recipients, and are lower in heart transplant patients under near-universal statin therapy. Of note, it is possible that mTOR inhibitors may offer a cardioprotective effect. Experimental evidence for delayed progression of atherosclerosis is consistent with evidence from heart transplantation that coronary artery intimal thickening and the incidence of cardiac allograft vasculopathy are reduced with everolimus versus cyclosporine therapy. Preliminary data also indicate that mTOR inhibitors may improve arterial stiffness, a predictor of cardiovascular events, and may reduce ventricular remodeling and decrease left ventricular mass through an anti-fibrotic effect. Post-transplant dyslipidemia under mTOR inhibitor therapy should be monitored and managed closely, but unless unresponsive to therapy should not be regarded as a barrier to its use. © 2014 Elsevier Inc.


Foss A.,University of Oslo | Adam R.,Center Hepato Biliaire | Dueland S.,University of Oslo
Transplant International | Year: 2010

Summary Liver transplantation (Lt) for colorectal cancer (CRC) liver metastases is no more considered due to the poor outcome observed up to the 1990s. According to the European Liver Transplant Registry (ELTR), 1- and 5-year patient survival following Lt for CRC liver metastases performed prior to 1995 was 62% and 18%, respectively. However, 44% of graft loss or patient deaths were not related to tumor recurrence. Over the last 20 years there has been dramatic progress in patient survival after Lt, thus it could be anticipated that survival after Lt for CRC secondaries today would exceed from far, the outcome of the past experience. By utilizing new imaging techniques for proper patient selection, modern chemotherapy and aggressive multimodal treatment against metastases, long term survivors and even cure could be expected. Preliminary data from a pilot study show an overall survival rate of 94% after a median follow up of 25 months. While long term survival after the first Lt is 80% all indications confounded, 5-year survival after repeat Lt is no more than 50% to 55%. If patients transplanted for CRC secondaries can reach the latter survival rate, it could be difficult to discriminate them in the liver allocation system and live donation could be an option. © 2010 European Society for Organ Transplantation.


Roche B.,Center Hepato Biliaire | Roche B.,French Institute of Health and Medical Research | Roche B.,University Paris - Sud | Samuel D.,Center Hepato Biliaire | And 2 more authors.
Seminars in Liver Disease | Year: 2012

Liver transplantation is the only therapy for patients with end-stage liver disease, hepatocellular carcinoma, or fulminant hepatitis due to hepatitis D virus (HDV) and hepatitis B virus (HBV) coinfection or superinfection. Patients chronically coinfected with HDV are less at risk of HBV recurrence and have a better survival rate than patients infected with HBV alone. Patients coinfected with HDV generally do not require pretransplant antiviral therapy. Rates of recurrent HBV-HDV infection are lower than 5% using low-dose intramuscular (IM) HBIg and antiviral prophylaxis in combination. Few studies have evaluated the possibility of using shorter-term HBIg (12-24 months) then switching to antiviral therapy. Although HBV replication can be controlled by potent HBV-polymerase inhibitors, reappearance of HBsAg and/or the persistence of HBV DNA in serum, liver, or peripheral blood mononuclear cells might have deleterious consequences in the setting of HBV-HDV coinfection as they may provide the biologic substrate to the reactivation of HDV. No effective antiviral drug is available for the treatment of graft infection with HDV. ©Copyright 2012 by Thieme MedicalPublishers, Inc.


Lee S.,The Surgical Center | Cherqui D.,Center Hepato Biliaire
Seminars in Liver Disease | Year: 2013

Cholangiocarcinomas (CCAs) are rare malignancies that originate from the epithelial cells of the bile ducts. It is the second most-common primary liver cancer after hepatocellular carcinoma. Recent epidemiologic studies have shown that the overall incidence and mortality rates of CCAs are increasing. Diagnosis is often challenging due to the difficulty in getting tissue/cytology for confirmation, and it comprises a combination of cross-imaging, tumor markers, histology, and cholangiography. Surgery involving major resections of liver, bile duct, pancreas, and at times adjacent vessels is the only chance for cure. Evaluation should be focused on the assessment of tumor resectability, hepatic reserve, and patient physiological fitness for major surgery. In patients not fit for major surgery, biliary drainage for jaundice is an appropriate intervention and if there is histologic confirmation of a CCA, palliative therapies focused on local and systemic disease control should be considered. The endeavor to expand the indications for liver transplantation reflects the efforts to provide an effective form of therapy for a previously untreatable disease. A multidisciplinary specialized approach should be the platform for providing the best comprehensive care for these patients. © 2013 by Thieme Medical Publishers, Inc.


Saliba F.,Center Hepato Biliaire | Camus C.,University of Rennes 2 – Upper Brittany | Durand F.,Assistance Publique Hopitaux de Paris Hopital Beaujon | Mathurin P.,Lille University of Science and Technology | And 7 more authors.
Annals of Internal Medicine | Year: 2013

Background: Albumin dialysis with the Molecular Adsorbent Recirculating System (MARS) (Gambro, Lund, Sweden), a noncell artificial liver support device, may be beneficial in acute liver failure (ALF). Objective: To determine whether MARS improves survival in ALF. Design: Randomized, controlled trial. (ClinicalTrials.gov: NCT00224705) Setting: 16 French liver transplantation centers. Patients: 102 patients with ALF. Intervention: Conventional treatment (n = 49) or MARS with conventional treatment (n = 53), stratified according to whether paracetamol caused ALF. Measurements: 6-month survival and secondary end points, including adverse events. Results: 102 patients (mean age, 40.4 years [SD, 13]) were in the modified intention-to-treat (mITT) population. The per-protocol analysis (49 conventional, 39 MARS) included patients with at least 1 session of MARS of 5 hours or more. Six-month survival was 75.5% (95% CI, 60.8% to 86.2%) with conventional treatment and 84.9% (CI, 71.9% to 92.8%) with MARS (P = 0.28) in the mITT population and 75.5% (CI, 60.8% to 86.2%) with conventional treatment and 82.9% (CI, 65.9% to 91.9%) with MARS (P = 0.50) in the per-protocol population. In patients with paracetamol-related ALF, the 6-month survival rate was 68.4% (CI, 43.5% to 86.4%) with conventional treatment and 85.0% (CI, 61.1% to 96.0%) with MARS (P = 0.46) in the mITT population. Sixty-six of 102 patients had transplantation (41.0% among paracetamol-induced ALF; 79.4% among non-paracetamol-induced ALF) (P < 0.001). Adverse events did not significantly differ between groups. Limitation: The short delay from randomization to liver transplantation (median, 16.2 hours) precludes definitive efficacy or safety evaluations. Conclusion: This randomized trial of MARS in patients with ALF was unable to provide definitive efficacy or safety conclusions because many patients had transplantation before administration of the intervention. Acute liver failure not caused by paracetamol was associated with greater 6-month patient survival. Primary Funding Source: Assistance Publique-Hôpitaux de Paris. © 2013 American College of Physicians.


Audrey C.,Center Hepato Biliaire | Raffaele B.,University of Pavia
Current Opinion in HIV and AIDS | Year: 2015

Purpose of review Liver transplantation is widely used to treat HIV patients with an end-stage liver disease, mainly decompensated cirrhosis and hepatocellular carcinoma. The results are good especially in non-hepatitis C virus (HCV)-coinfected patients. In HIV-HCV-coinfected patients, 5-year post-liver transplantation survival is around 50-55%, negatively impacted by HCV recurrence. The results of PEG-IFN/RBV are poor in terms of efficacy and safety. In patients with genotype 1 infection, triple therapy (boceprevir or telaprevir) has increased sustained virological response (SVR) rate, but drug-drug interactions (DDIs) with immunosuppressive agents and high rates of adverse events lead to forsake these combinations. Herein, we provide new data and practical management regarding HIV-HCV liver transplantation patients using new direct-acting antiviral agents (DAA). Recent findings The second-generation DAA have good safety profile. In patients who are candidates for liver transplantation or are already recipients, the optimal therapeutic option is to combine the new DAA. Efficacy results have dramatically improved with greater than 90% of SVR rate in many studies enrolling HCV-monoinfected liver transplant recipients. Some concerns persist in terms of DDI. Summary Even sparse, data regarding efficacy and safety of these regimens in HCV-HIV-coinfected liver transplantation will radically change the prognosis of this peculiar population. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Vibert E.,Center Hepato Biliaire
Journal of visceral surgery | Year: 2012

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. Developed on a pathological liver in 90% of cases, theoretically liver transplantation (LT) is its best treatment because it cures both malignancy and cause of malignancy, the underlying pathological liver. Cadaveric donors are the main source of liver in Western countries as France and living donors are the rules in Eastern countries as Japan. Because organ shortage could impact choices in HCC treatments, it was interesting to compare a Western and Eastern surgeon's points of view about treatment of HCC to assess if the source of organs has modified therapeutic strategies. Hence, aim of this work was to compare points of view of two hepatobiliary and transplant surgeons specialized in the treatment of HCC in France and Japan concerning five keys points that are decisive to choose one of the two curative treatments in HCC on pathological liver: liver resection or LT. These questions included the definition of an oncological treatment of HCC, the assessment of liver function, the treatment of HCC recurrences, the incidence of pathological information on therapeutic strategy and potential future therapeutics strategies. Copyright © 2012 Elsevier Masson SAS. All rights reserved.


Azoulay D.,Center Hepato Biliaire | Pascal G.,Center Hepato Biliaire | Salloum C.,Center Hepato Biliaire | Adam R.,Center Hepato Biliaire | And 2 more authors.
British Journal of Surgery | Year: 2013

Background The resectability criteria for malignant liver tumours have expanded during the past two decades. The use of vascular reconstruction after hepatectomy has been integral in this process. However, the majority of reports are anecdotal. This is a retrospective analysis of the techniques, morbidity, mortality and risk factors of liver resections with vascular reconstruction based on a large series from a single centre. Methods Patients who underwent hepatic resection combined with vascular resection and reconstruction between 1997 and 2009 were included in this study. Indications for surgery, morbidity and 90-day mortality are reported along with factors predictive of operative mortality. Results Eighty-four patients had liver resection with 97 vascular resections and reconstruction. There were 44 men and 40 women with a mean(s.d.) age of 56·9(12·1) years. Mean(s.d.) follow-up was 37·3(34·1) months. All patients had primary or metastatic liver tumours. The perioperative morbidity rate was 62 per cent (52 patients) and the operative mortality rate 14 per cent (12). Predictors of operative mortality were: bilirubin level exceeding 34 μmol/ml (P = 0·023), indocyanine green retention rate at 15 min over 10 per cent (P = 0·031), duration of ischaemia (P = 0·011), amount of blood transfused (P = 0·025) and combined major extrahepatic procedure (P = 0·042). Actuarial 3- and 5-year survival rates were 44 and 26 per cent respectively. Conclusion Liver resection with combined vascular resection and reconstruction can be performed in selected patients with acceptable morbidity and mortality. The lack of therapeutic alternatives and the poor outcome of non-operative management seem to justify this approach. The identification of risk factors should help improve patient selection and postoperative outcome as well as facilitate objective risk communication with surgical candidates. Extended liver resection of some benefit © 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.


Saliba F.,Center Hepato Biliaire
Expert Review of Anti-Infective Therapy | Year: 2012

Trends in Medical Mycology is one of the most attractive international meetings completely dedicated to clinical and fundamental research in the field of medical mycology. It is organized by the European Confederation of Medical Mycology and the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer. Approximately 1500 participants, mainly microbiologists, clinicians and basic researchers, from more than 40 countries exchanged the most important advances in mycology from basic science to clinical research. A quick focus on some relevant clinical presentations is presented here. © 2012 Expert Reviews Ltd.


Duclos-Vallee J.C.,Center Hepato Biliaire
Acta gastro-enterologica Belgica | Year: 2010

Liver transplantation (LT) is now feasible in HIV infected patients. To date, criteria of liver transplantation are no different from the other indications of liver transplantation; however an undetectable HIV viral load at the time of liver transplantation is desirable goal. History of opportunistic infections and CD4+ count < 100/mL do not constitute exclusion criteria. Long-term outcomes for HBV/HIV are excellent. Outcomes for HCV/HIV coinfected patients are more variable because of potentially severe recurrence on the liver graft. More effective antiviral therapy at an early stage post LT is required.

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