Pierre Bedossa

Paris Diderot University, Lutetia Parisorum, Île-de-France, France

Are you Pierre Bedossa?

Claim your profile

Publications (440)2043.03 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In Egypt, as elsewhere, liver biopsy (LB) remains the gold standard to assess liver fibrosis in chronic hepatitis C (CHC) and is required to decide whether a treatment should be proposed. Many of its disadvantages have led to develop noninvasive methods to replace LB. These new methods should be evaluated in Egypt, where circulating virus genotype 4 (G4), increased body mass index and co-infection with schistosomiasis may interfere with liver fibrosis assessment. Egyptian CHC-infected patients with G4 underwent a LB, an elastometry measurement (Fibroscan©), and serum markers (APRI, Fib4 and Fibrotest©). Patients had to have a LB ≥15 mm length or ≥10 portal tracts with two pathologists blinded readings to be included in the analysis. Patients with hepatitis B virus co-infection were excluded. Three hundred and twelve patients are reported. The performance of each technique for distinguishing F0F1 vs F2F3F4 was compared. The area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75 for APRI, Fib-4, Fibrotest© and Fibroscan©, respectively (no influence of schistosomiasis was noticed). An algorithm using the Fib4 for identifying patients with F2 stage or more reduced by nearly 90% the number of liver biopsies. Our results demonstrated that noninvasive techniques were feasible in Egypt, for CHC G4-infected patients. Because of its validity and its easiness to perform, we believe that Fib4 may be used to assess the F2 threshold, which decides whether treatment should be proposed or delayed.
    Journal of Viral Hepatitis 07/2014; · 3.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A simple and reproducible evaluation of non-diagnostic histological lesions related to prognosis remains crucial in primary biliary cirrhosis (PBC). Presently there is no satisfactory simple scoring system analyzing them reliably. We elaborated a semiquantitative scoring system that assesses fibrosis, lymphocytic interface hepatitis (LIH), and ductopenia, separately. This study was aimed to evaluate its intra/interobserver reproducibility and its correlation with the main biochemical data.
    Liver international: official journal of the International Association for the Study of the Liver 06/2014; · 3.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: No therapy for non-alcoholic steatohepatitis (NASH) has been approved so far. Roux-en-y gastric bypass (RYGB) is emerging as a therapeutic option, although its effect on NASH and related hepatic molecular pathways is unclear from human studies. We studied the effect of RYGB on pre-existent NASH and hepatic mitochondrial dysfunction-a key player in NASH pathogenesis-in a novel diet-induced mouse model nicely mimicking human disease.
    Gut 06/2014; · 10.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cirrhosis is a lesion at risk of hepatocellular carcinoma (HCC). Identifying mechanisms associated with the transition from cirrhosis to HCC and characterizing biomarkers of cirrhosis at high risk of developing into cancer are crucial for improving early diagnosis and prognosis of HCC. We used MALDI imaging to compare mass spectra obtained from tissue sections of cirrhosis without HCC, cirrhosis with HCC and HCC, and top-down proteomics approach to characterize differential biomarkers. We identified a truncated form of monomeric ubiquitin lacking the two C-terminal glycine residues, Ubi(1–74), the level of which increased progressively, from cirrhosis without HCC to cirrhosis with HCC, to HCC. We showed that kallikrein-related peptidase 6 (KLK6) catalyzed the production of Ubi(1–74) from monomeric ubiquitin. Furthermore, we demonstrated that KLK6 was induced de novo in cirrhosis and increased in HCC in parallel with accumulation of Ubi(1–74). We investigated in vitro the possible consequences of Ubi(1–74) accumulation, and demonstrated that Ubi(1–74) interferes with the normal ubiquitination machinery in what is likely to be a kinetic process. Our data suggests that de novo KLK6 expression during early liver carcinogenesis may induce production of Ubi(1–74) by post-translational modification of ubiquitin. Given the deleterious effect of Ubi(1–74) on protein ubiquitination and the major role of ubiquitin machinery in maintenance of cell homeostasis, Ubi(1–74) might severely impacts a number of critical cellular functions during transition from cirrhosis to cancer. Ubi(1–74), and KLK6 may serve as a marker of cancer risk in patients with cirrhosis.
    The Journal of Pathology 06/2014; · 7.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: AimsNeoadjuvant radiochemotherapy (RCT) followed by surgical resection is the treatment for locally advanced mid or low rectal cancer. The aim of this study was to evaluate postoperative histological prognostic factors in a series of surgical specimens after neoadjuvant RCT.Methods and results113 patients were included. Macroscopic and microscopic examinations were performed according to CAP recommendations, with additional criteria such as tumour budding, presence of calcifications and response to neoadjuvant therapy assessed by Modified Rectal Cancer Regression Grade (m-RCRG). 3-years DFS was 67.6%. In univariate analysis, ypTN stage, tumour budding, circumferential margin, invaded margin, vascular and perineural invasion were prognostic factors. In multivariate analysis, presence of calcifications (p=0.04) and involved circumferential margin (p=0.03) were the only independent factors of worse DFS. mRCRG was not correlated to DFS. Among the 50 m-RCRG1 tumours, DFS was better in ypT0 patients than in other ypT stages (p=0.003).Conclusions Presence of calcifications in tumour bed is a prognostic factor described for the first time in rectal cancer. Prognosis value of budding was demonstrated in this study after neoadjuvant RCT. ypT stage appears as a more reliable predictor of oncological outcome than histological tumour regression grade needing to be standardized for a better reproducibility.This article is protected by copyright. All rights reserved.
    Histopathology 04/2014; · 2.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Biopsy is still the gold standard for the diagnosis of nonalcoholic steatohepatitis but definition may vary among pathologists, a drawback especially in evaluation of biopsies for clinical trials. We previously developed a scoring system (SAF score) allowing the use of an algorithm (FLIP algorithm) for the classification of liver injury in morbid obesity. The aim of this study was to determine whether use of SAF score and FLIP algorithm can decrease interobserver variations among pathologists. In a first session, pathologists categorized 40 liver biopsies of patients with NAFLD according to their own experience. In a second reading session, each pathologist reclassified the same slides by using the FLIP algorithm and SAF score, blinded to their first evaluation. The experiment was repeated with two different groups of pathologists at varying levels of training in liver pathology. The percentage of biopsy interpretation concordant with reference evaluation increased from 77% to 97% in Group 1 and from 42% to 75% in Group 2 after the use of SAF score and FLIP algorithm. The strength of concordance in classification increased in Group 1 from moderate (κ = 0.54) to substantial (κ = 0.66) and from fair (κ=0.35) to substantial (κ=0.61) in Group 2 with application of the algorithm. With regards to SAF score, concordance was substantial in Group 1 for steatosis (κ=0.61), activity (κ=0.75), and almost perfect for fibrosis (κ=0.83 after pooling 1a, 1b and 1c together into a single score F1). Similar trends were observed in Group 2 (κ=0.54 for S, κ=0.68 for A and κ=0.72 for F).Conclusion: FLIP algorithm based on the SAF score should decrease interobserver variations among pathologists and are likely to be implemented in pathology practice. (Hepatology 2014)
    Hepatology 04/2014; · 12.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Mir-122 is highly expressed, in the liver, and stimulates Hepatitis C virus (HCV) replication, in vitro. IFNL3 polymorphisms and the expression of mir-122 have been associated with sustained virological response (SVR) to pegylated-interferon plus ribavirin, in patients with chronic hepatitis C (CHC). We investigated, in vivo, the relationship between mir-122 expression, IFNL3 polymorphism, fibrosis and response to treatment. Pre-treatment liver biopsies and serums from 133 patients with CHC were included. Sixty six patients achieved a SVR, and 64 failed to respond to the treatment (43 non-responders (NR) and 21 relapsers (RR)). All stages of fibrosis were represented, with 39, 50, 23, 19 patients respectively F1, F2, F3 and F4 (Metavir score). Mir-122 expression was assessed by RT-q-PCR and IFNL3 rs12979860 by direct sequencing. Hepatic mir-122 expression was higher in CC patients when compared to CT+TT, in total patients (p=0.025) and in NRs+RRs (p=0.013). Increased hepatic mir-122 was more strongly associated with complete early virological response (cEVR) (p=0.003) than with SVR (p=0.016). In multivariate analysis increased hepatic mir-122 was only associated with IFNL3 CC. Mir-122 was decreased in patients with F3-F4 as compared to patients with F1-F2 (p=0.01). Serum and hepatic expression of mir-122 were not associated. The association between mir-122 and IFNL3 is stronger than the association between mir-122 and response. Mir-122 may play a role in the early viral decline dependent of IFNL3 and innate immune response. Mir-122 plays a crucial role during HCV infection. Indeed, mir-122 binding within HCV genome stimulates its replication. Moreover, mir-122 is highly expressed within hepatocytes where it regulates many cellular pathways. A reduction of mir-122 expression has been suggested to be associated with responsiveness to IFN based therapy, in patients with chronic hepatitis C. Several independent genome wide association studies reported a strong association between IFNL3 polymorphism and responsiveness to IFN based therapy. We reported here a strong association between the expression of mir-122 and IFNL3 polymorphism, independently of the response to the treatment. Our data suggest that modification of mir-122 expression may play an important role in molecular mechanism associated with IFNL3 polymorphism. Moreover, we reported a reduction of mir-122 at more advanced stages of fibrosis, in patients with chronic hepatitis C.
    Journal of Virology 03/2014; · 5.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inactivation of the NF2 gene predisposes to neurofibromatosis type II and the development of schwannomas. In vitro studies have shown that loss of NF2 leads to the induction of mitogenic signaling mediated by receptor tyrosine kinases (RTKs), MAP kinase, AKT, or Hippo pathways. The goal of our study was to evaluate the expression and activity of these signaling pathways in human schwannomas in order to identify new potential therapeutic targets. Large sets of human schwannomas, totaling 68 tumors, were analyzed using complementary proteomic approaches. RTK arrays identified the most frequently activated RTKs. The correlation between the expression and activity of signaling pathways and proliferation of tumor cells using Ki67 marker was investigated by reverse-phase protein array (RRPA). Finally, immunohistochemistry was used to evaluate the expression pattern of signaling effectors in the tumors. We showed that Her2, Her3, PDGFRß, Axl, and Tie2 are frequently activated in the tumors. Furthermore, RRPA demonstrated that Ki67 levels are linked to YAP, p-Her3, and PDGFRß expression levels. In addition, Her2, Her3, and PDGFRß are transcriptional targets of Yes-associated protein (YAP) in schwannoma cells in culture. Finally, we observed that the expression of these signaling effectors is very variable between tumors. Tumor cell proliferation in human schwannomas is linked to a signaling network controlled by the Hippo effector YAP. Her2, Her3, PDGFRß, Axl, and Tie2, as well as YAP, represent potentially valuable therapeutic targets. However, the variability of their expression between tumors may result in strong differences in the response to targeted therapy.
    Neuro-Oncology 02/2014; · 6.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cholangiocarcinoma (CC) is the second most common primary malignancy of the liver. Although all CC derive from biliary epithelial cells, two main subtypes, hilar (H) and peripheral (P) CC are described. The objective of the study was to compare, using MALDI imaging mass spectrometry (MALDI IMS), in-situ proteomic profiles of H- and P-CC in order to assess whether these subtypes may express different markers and to describe their respective localizations. Twenty-seven CC (16 P-CC and 11 H-CC) were subjected to MALDI IMS. Proteomic data were submitted to a dedicated cross-classification comparative design, enabling comparison of the entire generated spectra. Immunohistochemistry was performed for validation. Comparative analysis yielded a list of 19 differential protein peaks for the two subtypes, 14 of which were overexpressed in H-CC and 5 in P-CC. Among H-CC protein markers, most discriminant were human neutrophil peptides 1-3 which were expressed mainly by tumor cells and S100 proteins (A6 and A11) which were restricted to the stromal area. In P-CC, thymosin β4 was diffusely overexpressed. These results highlight the potential of MALDI IMS to discover new relevant biomarkers of CC and to characterize the heterogeneity of the 2 different subtypes. This article is protected by copyright. All rights reserved.
    Proteomics 02/2014; · 4.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The normal liver has three major closely integrated compartments: hepatocytes, the biliary system and the vascular system. The first comprises 70% of the cells; the biliary system communicates throughout and outside the liver with immediately adjacent extra-hepatic organs and the last is, in many ways, the most complex of all three systems. The vascular system also communicates outside and throughout the liver. This article is protected by copyright. All rights reserved.
    Histopathology 01/2014; · 2.86 Impact Factor
  • Journal of hepatology. Supplement / EASL 01/2014; 60(1):S348.
  • Human pathology 01/2014; 45(3):658–660. · 3.03 Impact Factor
  • Source
    Tarik Asselah, Patrick Marcellin, Pierre Bedossa
    [Show abstract] [Hide abstract]
    ABSTRACT: The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
    Journal of Hepatology 01/2014; · 9.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background & Aims: ASP9831 is a phosphodiesterase-4 inhibitor developed to treat nonalcoholic steatohepatitis (NASH); it showed potent anti-inflammatory and anti-fibrotic effects in preclinical studies. We evaluated the efficacy and safety of ASP9831 in patients with NASH. Methods In a phase 1 trial, we determined the optimal therapeutic window of ASP9831 in healthy volunteers, and evaluated 2 doses (50 mg and 100 mg) in patients with NASH. Based on the positive outcomes of the phase 1 study, we performed a phase 2 trial, to compare the biochemical effects of ASP9831 vs placebo. Patients with NASH were randomly assigned to groups given either 50 mg (n = 33) or 100 mg (n = 33) ASP9831 twice-daily, or placebo (n = 30), for 12 wks. The primary end point was the mean percentage change, from baseline to end of ASP9831 administration, in serum level of alanine aminotransferase (ALT); secondary outcomes included changes in aspartate aminotransferase (AST) levels, ratio of AST:ALT, and various biomarkers of NASH. Results After 12 wks of administration, there was no significant change in mean serum levels of ALT (P=.42) or AST (P=.20) or other biomarkers in any group, and no significant differences were observed among groups. Most adverse events were mild; gastrointestinal disorders occurred more frequently in the ASP9831 groups than the placebo group. Conclusions Despite a relevant mechanism of action, ASP9831 did not significantly alter the biochemical markers of NASH, compared with placebo, in a clinical trial. This highlights the difficulties of developing therapeutics for NASH and need for a more extensive preclinical testing of mechanisms of potential drug candidates. Clinicaltrialsregister.eu, EudraCT numbers: 2005-001687-31 and 2007-002114-19.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 01/2014; · 5.64 Impact Factor
  • Pancreatology 01/2014; 14(3):S5. · 2.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context: Liver and white adipose tissue (WAT) develop inflammation and fibrosis. Objective: The aim of the study was to evaluate the bioclinical relevance of WAT fibrosis in morbid obesity and diabetes and the relationships with tissue stiffness measured using a novel device. Design and Setting: Observational and longitudinal studies were conducted in a hospital nutrition department. Patients: Biopsies of liver and subcutaneous WAT (scWAT) and omental adipose tissue were collected from 404 obese bariatric surgery candidates, of whom 243 were clinically characterized before surgery and 3, 6, and 12 months after surgery. In 123 subjects, liver and scWAT stiffness was assessed noninvasively using vibration-controlled transient elastography (VCTE). Interventions: Bariatric surgery was performed for some patients. Main Outcome Measure: Adipose tissue fibrosis and stiffness and their link to obesity phenotypes were measured. Results: scWAT fibrosis was positively associated with liver fibrosis (fibrosis score ≥ 2) ([GRAPHIC] = 0.14; P = .01). VCTE-evaluated liver and scWAT stiffness was positively correlated with immunohistochemistry-determined liver ([GRAPHIC] = 0.46; P = .0009) and scWAT fibrosis ([GRAPHIC] = 0.48; P = .0001). VCTE-evaluated scWAT stiffness measures negatively associated with dual-energy x-ray absorptiometry-evaluated body fat mass (R = -0.25; P = .009) and were correlated with metabolic variables. Diabetic subjects showed increased scWAT stiffness. Participants less responsive to gastric bypass were older and more frequently diabetic, and they had increased body mass index, serum IL-6, and scWAT and liver fibrosis. Subjects with no diabetes and normal liver had higher fat mass and lower tissue fibrosis and stiffness. Conclusion: scWAT stiffness was associated with tissue fibrosis, obesity, and diabetes-related traits. Noninvasive evaluation of scWAT stiffness might be useful in clinical practice.
    The Journal of Clinical Endocrinology and Metabolism 01/2014; · 6.31 Impact Factor
  • The American Journal of Gastroenterology 12/2013; 108(12):1937-8. · 7.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The impact of IFNL3 (IL28B) polymorphism on response to interferon (IFN) treatment in patients infected with hepatitis B virus (HBV) is controversial. We aimed to investigate whether IFNL3 polymorphism (rs12979860) influences the long-term response of chronic hepatitis B (CHB) treatment to conventional IFN. Design: Ninety-seven HBeAg-positive patients treated with IFN were evaluated in this study. Associations were investigated between IFNL3 genotypes and (i) HBeAg seroconversion at the end of treatment (EOT), (ii) sustained virological response (SVR) and (iii) HBsAg seroconversion through long-term follow-up (LTFU). Patients were followed for a median of 14 years. The majority of patients were infected with HBV genotype A (69.6%) and were Caucasian (77.9%). Ninety-five patients were genotyped at rs12979860. Similar IFNL3 distribution was observed among the different ethnicities (P = 0.62) or across HBV genotypes A through G (P = 0.70). Thirty-six patients experienced HBeAg seroconversion at EOT; HBeAg seroconversion rates were 37.0 and 35.5% in patients with CC and CT/TT genotypes, respectively (P = 0.82). Among the 44 patients (45%) who achieved a SVR, SVR rates were 48.9 and 39.6% in patients with CC and CT/TT IL28B genotypes, respectively (P = 0.80). HBsAg seroconversion occurred through LTFU in 28 patients. HBsAg seroconversion rates were 25.5 and 31.2% in patients with CC and CT/TT genotypes, respectively (P = 0.51). No significant relationship between IFNL3 rs12979860 and fibrosis stage was observed (P = 0.85). IFNL3 genotype was neither associated with SVR, nor with HBeAg seroconversion and long-term HBsAg seroconversion in HBeAg-positive CHB patients responding to IFN therapy.
    Journal of Viral Hepatitis 10/2013; · 3.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Microvascular invasion (MiVI) is a major risk factor in post-operative tumor recurrence and mortality in hepatocellular carcinomas (HCC). Unfortunately, this histological feature is usually missed by liver biopsy because of limited sampling, and MiVI is commonly detected only after surgery and examination of the full resected specimen. To date, there exists no reliable tool for identifying MiVI prior to surgical procedures. This study aimed to compare the proteome of HCC with and without MiVI in order to identify surrogate biomarkers of MiVI. A training cohort comprising surgically resected primary HCC with MiVI (n=30) and without MiVI (n=26) was subjected to MALDI imaging mass spectrometry (MALDI IMS). Comparative analysis of acquired mass spectra of the two groups yielded 30 differential protein peaks, among which 28 were more strongly expressed in HCC with MiVI. Among these, two peaks were identified as N-term acetylated histone H4 dimethylated at lysine (K) 20, and N-term acetylated histone H4 dimethylated at K20 and acetylated at K16. Both peaks were validated in the training cohort and in an independent validation cohort (n=23) by immunohistochemistry and western blot. Conclusion: These results demonstrate the potential of MALDI IMS for uncovering new relevant biomarkers of MiVI in HCC, and highlight the role of epigenetic modifications in the prognosis of HCC. Pre-operative detection of modified forms of histone H4 expression in tumor biopsies would be helpful in management of patients with HCC. (HEPATOLOGY 2013.).
    Hepatology 04/2013; · 12.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND & AIM: Transient elastography (TE) is a validated non-invasive tool to evaluate hepatic fibrosis in patients with hepatitis C virus (HCV) infection. Whether TE may sense changes of liver fibrosis following therapeutic HCV eradication has never been evaluated. MATERIALS AND METHODS: 38 HCV cirrhotics with paired pre- and post-sustained virological response (SVR) liver biopsies (LB) underwent TE at the time of post-SVR LB. Liver fibrosis was staged with the METAVIR scoring system and the area of fibrosis (%) was assessed morphometrically. RESULTS: Thirty-three patients had valid TE measurements after 61 (48-104) months from an SVR, and 20 (61%) of them had cirrhosis regression. On post-SVR LB, the median area of fibrosis was 2.3%, being significantly reduced from baseline (p<0.0001). Median TE value was 9.8 kPa being lower in regressed vs not regressed patients (9.1 kPa vs 12.9 kPa, p=0.01). TE was <12 kPa in 5 (38%) F4 patients and in 19 (95%) ⩽ F3 patients (p=0.0007). The diagnostic accuracy of TE for diagnosing F4 after treatment was 58% sensitivity, 90% specificity, 6.1 LR +, 0.4 LR-, AUROC 0.77. A significant correlation was found between TE and both fibrosis stage (r=0.56; p=0.001) and morphometry (r=0.56, p=0.001) as well as between fibrosis stage and area of fibrosis (r=0.72, p=0001). CONCLUSIONS: Following therapeutic eradication of HCV, the predictive power of the viremic cut-off of 12 kPa was low as a consequence of liver remodelling and fibrosis reabsorption. LB still remains the only reliable approach to stage liver fibrosis following an SVR.
    Journal of Hepatology 03/2013; · 9.86 Impact Factor

Publication Stats

14k Citations
2,043.03 Total Impact Points

Institutions

  • 2008–2014
    • Paris Diderot University
      • Centre de recherche biomédicale Bichat, Beaujon (CRB3) UMR-S 773
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Grenoble
      Grenoble, Rhône-Alpes, France
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2001–2014
    • Assistance Publique – Hôpitaux de Paris
      • Department of Radiology
      Lutetia Parisorum, Île-de-France, France
  • 2012
    • Centre de Recherche des Cordeliers de Jussieu (CRC)
      Lutetia Parisorum, Île-de-France, France
    • University of Milan
      • Department of Internal Medicine
      Milano, Lombardy, Italy
  • 2011
    • University of Bordeaux
      Burdeos, Aquitaine, France
  • 2008–2011
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2007–2011
    • Hôpital Beaujon – Hôpitaux Universitaires Paris Nord Val de Seine
      • Service de Pancréato-Gastroentérologie
      Clicy, Île-de-France, France
  • 2010
    • German Diabetes Center
      • Institute of Clinical Biochemistry and Pathobiochemistry
      Düsseldorf, North Rhine-Westphalia, Germany
    • Trinity College Dublin
      Dublin, Leinster, Ireland
  • 2009
    • Alphabio
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Université de Versailles Saint-Quentin
      Versailles, Île-de-France, France
  • 1994–2008
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • Universität Regensburg
      • Lehrstuhl für Innere Medizin I
      Regensburg, Bavaria, Germany
  • 1987–2006
    • Hôpital Antoine-Béclère – Hôpitaux universitaires Paris-Sud
      Clamart, Île-de-France, France
  • 2005
    • Université René Descartes - Paris 5
      • Faculté des Sciences Pharmaceutiques et Biologiques de Paris
      Paris, Ile-de-France, France
    • University of California, San Diego
      • Department of Medicine
      San Diego, CA, United States
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France
  • 1998–2005
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 1999
    • Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud)
      Lutetia Parisorum, Île-de-France, France
  • 1997
    • Centre Hospitalier Universitaire d'Angers
      • Service d'hépatologie gastro-entérologie
      Angers, Pays de la Loire, France
  • 1995–1997
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service d’Hépato - Gastro - Entérologie
      Paris, Ile-de-France, France