Didier Samuel

Université Paris-Sud 11, Orsay, Île-de-France, France

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Publications (621)3732.34 Total impact

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    ABSTRACT: Objectives In France, decisions regarding Super-Urgent Liver Transplantation in patients with acute liver failure (ALF) are principally based on the Clichy-Villejuif (CV) criteria. The aims of the present study were to study the outcomes of patients registered for a SU liver transplant and factors predictive of a spontaneous improvement, and to determine the usefulness of the Clichy-Villejuif criteria. Methods All patients listed in France for Super-Urgent (SU) LT between 1997 and 2010, aged 15 years and over with ALF, were included. Results 808 patients were listed for SU transplantation, 22% with paracetamol-induced and 78% with non-paracetamol-induced ALF. Of these 808 patients, 112 improved spontaneously, 587 underwent LT and 109 died. The one-year survival rate under intention-to-treat analysis and the survival after LT was 66.3% [62.7-69.7] and 74.2% (70.5-77.6) respectively. Factors predictive of a spontaneous recovery with ALF-related paracetamol hepatotoxity were: hepatic encephalopathy grade 0, 1 or 2, (OR=4.8; 95% CI (1.99-11.6)), creatinine clearance >60ml/min/1.73m(2) , (4.77; 95% CI (1.96-11.63)), a bilirubin level <200 µmol/l, (21.64; 95% CI (1.76-265.7)) and factor V level >20%, (5.79 95% CI (1.66-20.29); and for ALF-related non-paracetamol hepatotoxity: bilirubin level <200 µmol/l, (10.38; 95% CI (4.71-22.86)). The sensitivity, specificity, and positive and negative predictive values for the CV criteria were 75%, 56%, 50% and 79%, and 69%, 50%, 64% and 55%, respectively, for ALF due to, or not related to, paracetamol. Conclusion The performance of current criteria for SU transplantation could be improved by splitting paracetamol-induced and non-paracetamol-induced ALF and by including two other items in this model: the bilirubin level and creatinine clearance. This article is protected by copyright. All rights reserved. © 2015 American Association for the Study of Liver Diseases.
    Liver Transplantation 02/2015; · 3.79 Impact Factor
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    ABSTRACT: This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data. © 2015 The Authors. American Journal of Transplantation Published by Wiley Periodicals, Inc.
    American Journal of Transplantation 02/2015; 15(XX):1-16. · 6.19 Impact Factor
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    ABSTRACT: Immunization against meningococcal disease is recommended for solid organ transplant (SOT) recipients at high risk for meningococcal disease or travelling to an endemic country. However, the immunogenicity of meningococcal vaccines has not been studied in this population. We analyzed the immune response of quadrivalent (against Neisseria meningitidis serogroups A, C, Y, and W) polysaccharidic non-conjugate and conjugate meningococcal vaccines in kidney- and liver-transplant patients using bactericidal assays against the targeted serogroups. Upon vaccination with a non-conjugate (n = 5) or a conjugate vaccine (n = 10), respectively, 40% and 50% of patients were able to mount an immune response, achieving at least the threshold correlated with protection defined as human serum bactericidal antibody titers of ≥4. Responders showed only partial and low responses (titers ≤64), thus predicting a rapid decline in bactericidal response. Only 1 patient developed a booster response to preexisting immunity. Our data argue for the need of additional measures for SOT recipients, when they are at risk of meningococcal disease.This article is protected by copyright. All rights reserved.
    Transplant Infectious Disease 01/2015; · 1.98 Impact Factor
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    ABSTRACT: To investigate the prognostic significance of pathologic response (PR) after transarterial chemoembolization (TACE) in cirrhotic patients resected or transplanted for hepatocellular carcinoma (HCC) and to identify predictors of complete pathologic response (CPR).
    Journal of Hepatology. 01/2015;
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    ABSTRACT: To assess within the ANRS CO20-CUPIC cohort whether the viral load (VL) at week2/week6 for telaprevir/boceprevir-based triple therapy, respectively, was predictive of sustained virological response (SVR) in patients with hepatitis C virus (HCV) infection and to study the relevance of this measurement to early diagnose drug resistance. Observational study of HCV genotype 1 patients with compensated cirrhosis (Child-Pugh A), non-responders to a prior course of interferon (IFN)-based therapy and who started triple therapy. Patients received either 12weeks of telaprevir in combination with PEG-IFN/ribavirin (RBV), then 36weeks of PEG-IFN/RBV, or 4weeks of PEG-IFN/RBV, then 44weeks of PEG-IFN/RBV and boceprevir. A total of 262 patients were analyzed. For telaprevir-treated patients, 28% had undetectable VL at W2 of whom 81% achieved SVR12 whereas 67% had undetectable VL at W4 of whom 67% achieved SVR12. For boceprevir-treated patients 20% had undetectable VL at W6 and 86% of them achieved SVR12 whereas 36% had undetectable VL at W8 among whom 73% achieved SVR12. Five telaprevir-treated patients had a VL increase between W2 and W4 after a decrease between D0 and W2. Four of them did not achieve SVR12. Similarly, six boceprevir-treated patients had a VL increase between W6 and W8 after a decrease between D0 and W6. Five did not reach SVR12. The assessment of HCV RNA level after two weeks of triple therapy in cirrhotic non-responder patients is a good predictor of SVR. This assessment was useful to do an early diagnosis of viral breakthrough. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    Clinics and research in hepatology and gastroenterology. 01/2015;
  • Bruno Roche, Didier Samuel
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    ABSTRACT: Altered aerobic capacity and muscular strength among patients suffering from cirrhosis are poor prognosis factors of the overall survival after liver transplantation (LT). A program of adapted physical activity (APA) is recommended in patients awaiting solid organ transplantation. However, there is no standard program in LT, and therefore none is applied. Prospective pilot study to evaluate the acceptability of a 12-week personalized APA and its impact on aerobic capacity, muscle strength, and quality of life before LT. Thirteen patients (six men, seven women) were included. Five patients interrupted the program: two for personal convenience, two were transplanted before the end of the program, and one for deterioration of the general condition. Eight patients (mean age, 51±12 years; mean Child Pugh, 7±3; and mean model for end-stage liver disease score, 13±6) completed the program. The mean VO2 peak values increased from 21.5±5.9 mL/kg per min at baseline to 23.2±5.9 mL/kg per min after 12 weeks of training (P<0.008). The maximum power (P=0.02), the 6-min walk distance (P<0.02), the strength testing of knee extensor muscles (P=0.008), and the ventilatory threshold power (P=0.02) were also significantly increased. Quality of life scale showed a global trend to improvement. No adverse event was observed. A personalized and standardized APA is acceptable, effective and safe in patients awaiting LT. It positively influences the index of fitness and quality of life. Its promising impact on the posttransplantation period, duration of hospitalization, and 6-month survival needs to be prospectively evaluated in a large randomized study.
    Transplantation 01/2015; 99(1):145-50. · 3.78 Impact Factor
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    ABSTRACT: Simeprevir (SMV) is a once-daily (QD), oral hepatitis C virus (HCV) NS3/4A protease inhibitor approved for treatment of genotype (GT)1 and GT4 infection. This Phase III, open-label, single-arm study (RESTORE; NCT01567735) evaluated efficacy/safety of SMV with peginterferon-α-2a/ribavirin (PR) in patients with chronic HCV GT4 infection. 107 patients were included. Treatment-naïve (n=35) and prior relapse patients (n=22) received SMV 150mg QD+PR (12weeks), followed by PR alone (12 or 36 weeks, response-guided [HCV RNA <25IU/mL detectable/undetectable at Week 4 and <25 IU/mL undetectable at Week12]). Prior non-responders (partial, n=10; null, n=40) received SMV/PR (12weeks), followed by PR for 36 weeks. The primary endpoint was sustained virologic response 12 weeks after end of treatment (SVR12). Median age: 49.0 years; 28.0% Black/African; 7.5% IL28B CC; 28.8% METAVIR F4. Overall, 65.4% (70/107) of patients achieved SVR12 (82.9% [29/35] treatment-naïve; 86.4% [19/22] prior relapsers; 60.0% [6/10] prior partial responders; 40.0% [16/40] prior null responders). In treatment-naïve and prior relapser patients fulfilling response-guided criteria for 24 weeks of treatment (88.6% [31/35] and 90.9% [20/22]), SVR12 rates were high: 93.5% [29/31] and 95.0% [19/20], respectively. Overall on-treatment failure and relapse rates were 23.4% (25/107) and 14.6% (12/82), respectively. Adverse events (AEs) were mainly grade 1/2; serious AEs were infrequent (4.7%) and considered unrelated to SMV. Efficacy and safety of SMV 150mg QD for 12 weeks with PR in treatment-naïve or -experienced patients with chronic HCV GT4 infection were in line with previous reports for HCV GT1 infection. Copyright © 2015. Published by Elsevier B.V.
    Journal of hepatology. 01/2015;
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    ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a frequent lesion associated with obesity, diabetes and the metabolic syndrome. The hallmark feature of fatty liver disease is steatosis, which is the intra-cellular accumulation of lipids resulting in the formation of vesicles in hepatocytes. Steatosis is a precursor of steatohepatitis, a condition that may progress to hepatic fibrosis, cirrhosis and primary liver cancer. We addressed the potential of Fourier transform-infrared (FTIR) microspectroscopy for grading steatosis on frozen tissue sections. The use of the bright infrared source emitted by synchrotron radiation (SR) allowed the investigation of the biochemical composition at the cellular level. The variance in the huge number of spectra acquired was addressed by principal component analysis (PCA). The study demonstrated that the progression of steatosis corresponds not only to the accumulation of lipids but also to dramatic changes in the qualitative composition of the tissue. Indeed, a lower grade of steatosis showed a decrease in glycogen content and a concomitant increase in lipids in comparison with normal liver. Intermediate steatosis exhibited an increase in glycogen and major changes in lipids, with a significant contribution of esterified fatty acids with elongated carbon chains and unsaturated lipids, and these features were more pronounced in a high grade of steatosis. Furthermore, the approach allows a systematic discrimination of morphological features, leading to a separate investigation of steatotic vesicles and the non-steatotic counterpart of the tissue. This highlighted the fact that dramatic biochemical changes occur in the non-steatotic part of the tissue also despite its normal histological aspect, suggesting that the whole tissue reflects the grade of steatosis.
    The Analyst 01/2015; · 3.91 Impact Factor
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    ABSTRACT: Background. Until recently, liver transplantation (Ltx) was the only available treatment for hereditary transthyretin (TTR) amyloidosis; today, however, several pharmacotherapies are tested. Herein, we present survival data from the largest available database on transplanted hereditary TTR patients to serve as a base for comparison. Methods. Liver transplantation was evaluated in a 20-year retrospective analysis of the Familial Amyloidosis Polyneuropathy World Transplant Registry. Results. From April 1990 until December 2010, data were accumulated from 77 liver transplant centers. The Registry contains 1940 patients, and 1379 are alive. Eighty-eight Ltx were performed in combination with a heart and/or kidney transplantation. Overall, 20-year survival after Ltx was 55.3%. Multivariate analysis revealed modified body mass index, early onset of disease (<50 years of age), disease duration before Ltx, and TTR) Val30Met versus non-TTR Val30Met mutations as independent significant survival factors. Early-onset patients had an expected mortality rate of 38% that of the late-onset group (P < 0.001). Furthermore, Val30Met patients had an expected mortality rate of 61% that of non-TTR Val30Met patients (P < 0.001). With each year of duration of disease before Ltx, expected mortality increased by 11% (P < 0.001). With each 100-unit increase in modified body mass index at Ltx, the expected mortality decreased to 89%of the expectedmortality (P < 0.001). Cardiovascular death wasmarkedlymore common than that observed in patients undergoing Ltx for end-stage liver disease. Conclusions. Long-term survival after Ltx, especially for early-onset TTR Val30Met patients, is excellent. The risk of delaying Ltx by testing alternative treatments, especially in earlyonset TTR Val30Met patients, requires consideration.
    Transplantation 01/2015; · 3.78 Impact Factor
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    ABSTRACT: Malnutrition is an independent risk factor of postoperative morbidity and mortality and it's observed in 20 to 50% of surgical patients. Preoperative interventions to optimize the nutritional status, reduce postoperative complications and enteral nutrition has proven to be superior to the parenteral one. Moreover, regardless of the nutritional status of the patient, surgery impairs the immunological response, thus increasing the risk of postoperative sepsis. Immunonutrition has been developed to improve the immunometabolic host response in perioperative period and it has been proven to reduce significantly postoperative infectious complications and length of hospital stay in patients undergoing elective gastrointestinal surgery for tumors. We hypothesize that a preoperative oral immunonutrition (ORAL IMPACT(R)) can reduce postoperative morbidity in liver resection for cancer.Methods/design: Prospective multicenter randomized placebo-controlled double-blind phase IV trial with two parallel treatment groups receiving either study product (ORAL IMPACT(R)) or control supplement (isocaloric isonitrogenous supplement - IMPACT CONTROL(R)) for 7 days before liver resection for cancer. A total of 400 patients will be enrolled. Patients will be stratified according to the type of hepatectomy, the presence of chronic liver disease and the investigator center. The main end-point is to evaluate in intention-to-treat analysis the overall 30-day morbidity. Secondary end-points are to assess the 30-day infectious and non-infectious morbidity, length of antibiotic treatment and hospital stay, modifications on total food intake, compliance to treatment, side-effects of immunonutrition, impact on liver regeneration and sarcopenia, and to perform a medico-economic analysis. The overall morbidity rate after liver resection is 22% to 42%. Infectious post-operative complications (12% to 23%) increase the length of hospital stay and costs and are responsible for a quarter of 30-day mortality. Various methods have been advocated to decrease the rate of postoperative complications but there is no evidence to support or refute the use of any treatment and further trials are required. The effects of preoperative oral immunonutrition in non-cirrhotic patients undergoing liver resection for cancer are unknown. The present trial is designed to evaluate whether the administration of a short-term preoperative oral immunonutrition can reduce postoperative morbidity in non-cirrhotic patients undergoing liver resection for cancer.Trial registration: Clinicaltrial.gov: NCT02041871.
    BMC Cancer 12/2014; 14(1):980. · 3.32 Impact Factor
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    ABSTRACT: Background and AimsIn patients with cirrhosis, the risk of hepatocellular carcinoma (HCC) depends upon age, gender and the etiology of liver disease. Few studies are available in Caucasian patients with alcoholic or metabolic cirrhosis without viral hepatitis.Methods Cross sectional clinical data from 905 HCV- and HBV-negative Caucasian patients with alcoholic or metabolic cirrhosis were prospectively collected in 4 French centers. The risk factors for HCC were identified by logistic regression analysis in the whole population and in a nested case-control study.ResultsThe etiology of cirrhosis was alcoholic (48%), metabolic (7%) or mixed (45%). Patients were predominantly male (80%), mean age 62 years old and 31% had HCC. Mean body mass index (BMI) was 27 ± 5 and 30% were obese at inclusion. The maximum BMI reached throughout life was 31 ± 6 and 63% had been obese. Ninety percent of the population had daily alcohol consumption, 73% were smokers.HCC was independently related to male gender (p<0.0001), older age (p <0.0001), past obesity (p=0.007), diabetes (p=0.037), abnormal levels of transaminases (p<0.0001) and tobacco consumption (p=0.007). The case-control study (200 HCC cases matched with 400 non-HCC cases for gender, age and Child-Pugh score) confirmed past obesity, tobacco and abnormal levels of transaminases.Conclusions Beside diabetes, male gender and age, a past history of obesity, but not an existing overweight, as well as exposure to tobacco and elevated transaminases were three risk factors which could improve the strategy for HCC screening in Caucasian cirrhotic patients without hepatitis B or C.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 12/2014; · 4.41 Impact Factor
  • Gastroenterology 11/2014; · 13.93 Impact Factor
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    ABSTRACT: Cirrhotic patients with acute decompensation frequently develop acute-on chronic liver failure (ACLF), which is associated with high mortality rates. Recently, a specific score for these patients has been developed using the CANONIC study database. The aims of this study were to develop and validate the CLIF-C AD score, a specific prognostic score for hospitalised cirrhotic patients with acute decompensation (AD) but without ACLF and, to compare this with the Pugh, MELD and MELD-Na scores. The derivation set included 1,016 CANONIC study patients without ACLF. Proportional hazards models considering liver transplantation as a competing risk was used to identify score parameters. Estimated coefficients were used as relative weights to compute the CLIF-C ADs. External validation was performed in 225 cirrhotic AD patients. CLIF-C ADs was also tested for sequential use. Age, serum sodium, white-cell count, creatinine and INR were selected as the best predictors of mortality. The C-index for prediction of mortality was better for CLIF-C ADs compared with Pugh, MELD and MELD-Nas at predicting 3- and 12-month mortality in the derivation, internal validation and the external dataset. CLIF-C ADs improved in its ability to predict 3-month mortality using data from days 2, 3-7 and 8-15 (C-index: 0.72; 0.75 and 0.77 respectively). The new CLIF-C ADs is more accurate than other liver scores in predicting prognosis in hospitalised cirrhotic patients without ACLF. CLIF-C ADs therefore may be used to identify a high-risk cohort for intensive management and a low-risk group that may be discharged early. Copyright © 2014. Published by Elsevier B.V.
    Journal of Hepatology 11/2014; · 10.40 Impact Factor
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    Didier Samuel
    Journal of Hepatology 11/2014; · 10.40 Impact Factor
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    ABSTRACT: Severe hepatitis C virus (HCV) recurrence affects post-transplant survival in HIV/HCV co-infected patients. This article describes the results of triple anti-HCV therapy with boceprevir or telaprevir in seven HIV/HCV co-infected patients following liver transplantation.
    AIDS (London, England) 11/2014; · 6.56 Impact Factor
  • F Saliba, D Samuel
    Minerva medica 11/2014; · 1.20 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) end stage liver disease is a main indication for liver transplantation (LT). Recurrent HCV always occurs when patients are transplanted with a detectable viral load, leading to cirrhosis in 20 to 30% of patients within 5 years. Achieving a sustained virological response (SVR) with antiviral treatment is the only way to improve patient and graft survival. Dual therapy based on pegylated interferon and ribavirin (PEG-IFN/RBV) was the standard of care for many years with limited efficacy and a poor safety profile. The addition of first generation NS3/4 protease inhibitors (PI) improved SVR rates from 30% to 50%-60%. But the occurrence of serious adverse events (AEs) and drug-drug interactions with calcineurin inhibitors (CNI) have both been limiting factors for their use during LT. The preliminary results of the use of second generation direct acting antivirals (DAA) in transplant patients showed better efficacy with an SVR rate >70%. The pre- and post-transplantation safety profile is good. Although fewer drug-drug interactions are expected, some new DAA still interact with immunosuppressive drugs. Certain questions such as the use of RBV or the optimal duration of therapy have still not been resolved but should be answered by the many ongoing studies in the coming year.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 11/2014; · 4.41 Impact Factor
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    ABSTRACT: Interferon alfa-based regimens used to treat recurrent hepatitis C virus (HCV) infection after liver transplantation are poorly tolerated, associated with generally modest efficacy, and can interact with immunosuppressive agents. We evaluated the efficacy and safety of an interferon-free regimen of the nucleotide polymerase inhibitor sofosbuvir combined with ribavirin for 24 weeks in treating post-transplant HCV infection.
    Gastroenterology 10/2014; · 12.82 Impact Factor
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    ABSTRACT: Background Post-transplant non-Hodgkin lymphoma (NHL) is a well-recognized complication of solid organ transplantation, and pharmacologic suppression of adaptive immunity plays a major role in its development. However, the role of natural killer (NK) cells in post-lung transplant de novo NHL is unknown. Methods Extensive phenotypic analyses of NK cells from patients diagnosed with NHL after liver or lung transplantation were conducted with multicolor flow cytometry. Polyfunctionality assays simultaneously assessed NK-cell degranulation (CD107a) and intracellular cytokine production (IFN-γ and TNF-α) in the presence of NHL target cells. Results The development of de novo NHL is linked to NK-cell maturation defects, including overexpression of NKG2A and CD62L and down-modulation of inhibitory killer immunoglobulin-like receptors and CD57 receptors. More Importantly, in patients who developed NHL after lung transplantation, we observed a specific down-modulation of the activating receptors (NKp30, NKp46, and NKG2D), and a sharp decrease in perforin expression and degranulation against NHL target cells. Conclusion Our results suggest that accumulation of abnormal NK cells could play a role in the outgrowth of NHL after lung transplantation, independently of the immune-suppressive regimen.
    The Journal of Heart and Lung Transplantation 10/2014; · 5.61 Impact Factor

Publication Stats

12k Citations
3,732.34 Total Impact Points


  • 1991–2015
    • Université Paris-Sud 11
      • • Faculty of Medicine
      • • Service de Pneumologie
      Orsay, Île-de-France, France
  • 2008–2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 1997–2014
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 1990–2014
    • Hôpital Paul-Brousse – Hôpitaux universitaires Paris-Sud
      Île-de-France, France
    • Groupe Hospitalier Paul Guiraud
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • King's College London
      Londinium, England, United Kingdom
  • 1999–2013
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Yale-New Haven Hospital
      New Haven, Connecticut, United States
    • Hôpital Saint-Antoine (Hôpitaux Universitaires Est Parisien)
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud)
      Lutetia Parisorum, Île-de-France, France
    • Université René Descartes - Paris 5
      Lutetia Parisorum, Île-de-France, France
    • University of Lille Nord de France
      Lille, Nord-Pas-de-Calais, France
  • 2009
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      Créteil, Île-de-France, France
  • 2007
    • Baylor College of Medicine
      • Department of Surgery
      Houston, TX, United States
  • 2005
    • University of California, San Francisco
      San Francisco, California, United States
  • 2001
    • CHU de Lyon - Hôpital de la Croix-Rousse
      Lyons, Rhône-Alpes, France
  • 1996
    • Osaka Medical College
      Takatuki, Ōsaka, Japan
  • 1995
    • Hadassah Medical Center
      • Department of Medicine
      Jerusalem, Jerusalem District, Israel
  • 1993
    • University of Florence
      • Dipartimento di Medicina Sperimentale e Clinica
      Florens, Tuscany, Italy
  • 1990–1993
    • Institut Pasteur
      Lutetia Parisorum, Île-de-France, France
  • 1989
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France