D Valla

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

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Publications (368)2130.64 Total impact

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    ABSTRACT: Purpose To prospectively compare the technical success rate and accuracy of shear-wave elastography ( SWE shear-wave elastography ) and transient elastography ( TE transient elastography ) for the detection of clinically significant portal hypertension ( PH portal hypertension ) in patients with advanced cirrhosis who are undergoing hepatic vein pressure gradient ( HVPG hepatic vein pressure gradient ) measurements. Materials and Methods The institutional ethics committee approved the study, and written informed consent was obtained. Seventy-nine consecutive patients with cirrhosis who were undergoing SWE shear-wave elastography and TE transient elastography at the time of HVPG hepatic vein pressure gradient measurement were studied. The technical success rate of SWE shear-wave elastography and TE transient elastography was compared with the diagnostic value of liver stiffness ( LS liver stiffness ) and spleen stiffness ( SS spleen stiffness ) measurements and composite scores ( LS liver stiffness spleen-diameter-to-platelet-ratio score [ LSPS LS spleen-diameter-to-platelet-ratio score ] and PH portal hypertension risk score) by using SWE shear-wave elastography and TE transient elastography to detect clinically significant PH portal hypertension ( HVPG hepatic vein pressure gradient ≥ 10 mm Hg) and esophageal varices at high risk of bleeding. Areas under the receiver operating characteristic curve and the DeLong test were used. Results The technical success rate of SWE shear-wave elastography was significantly better than that of TE transient elastography for both LS liver stiffness and SS spleen stiffness (97% and 97% vs 44% and 42%, respectively; P < .001). LS liver stiffness of more than 24.6 kPa with SWE shear-wave elastography had a sensitivity, specificity, and accuracy for clinically significant PH portal hypertension of 81%, 88%, and 82%, respectively. Diagnostic performance of LS liver stiffness by using SWE shear-wave elastography was significantly better than that for SS spleen stiffness for the diagnosis of clinically significant PH portal hypertension (area under the receiver operating characteristic curve of 0.87 vs 0.64, P = .003). LS liver stiffness , SS spleen stiffness , LSPS LS spleen-diameter-to-platelet-ratio score , and PH portal hypertension risk score (according to SWE shear-wave elastography or TE transient elastography ) did not differ between patients with and those without high-risk esophageal varices (P = .09-.42). Conclusion In patients with advanced cirrhosis who are undergoing HVPG hepatic vein pressure gradient measurements, LS liver stiffness measurements obtained by using SWE shear-wave elastography have a higher technical success rate and a better diagnostic value than TE transient elastography for clinically significant PH portal hypertension . © RSNA, 2014 Online supplemental material is available for this article.
    Radiology 11/2014; · 6.34 Impact Factor
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    ABSTRACT: The beneficial effect of achieving a sustained virologic response (SVR) after antiviral treatment against hepatitis C virus is well established. However it remains unclear whether unsuccessful treatment (non-SVR) also improves patient's survival, especially in patients with advanced liver fibrosis. We retrospectively evaluated the incidence of death or liver transplantation in the 427 naïve Child A patients with advanced fibrosis newly admitted in our hospital between 2000 and 2010. Patients were followed for a median time of 5.5 years. Baseline characteristics of untreated (N=102) and treated (N=325) patients were largely similar and there was no evidence of a bias of indication. Treated patients received a combination of interferon and ribavirin with a SVR rate of 32%. The incidence of death or liver transplantation per 100 person-years was 1.00, 3.20 and 5.44 in SVR, non-SVR and untreated patients, respectively. After adjusting on baseline characteristics the risk of death or liver transplantation was significantly lower in SVR than in non-SVR patients and in non-SVR than in untreated patients (hazard ratio equal to 0.35 and 0.51, respectively; p=0.019 and 0.038, respectively). The effect of treatment in non-SVR patients was higher in patients who had a virological or a biochemical response than in those who did not have a virological or a biochemical response. The risk of death or liver transplantation was significantly lower in treated than in untreated patients. Moreover there was a gradient of mortality between SVR, virological or biochemical responders and untreated patients, suggesting that treatment, even in absence of viral eradication, has a beneficial effect on survival. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 11/2014; · 4.57 Impact Factor
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    ABSTRACT: Background & Aims: In cirrhosis, portal vein thrombosis (PVT) could be a cause or a consequence of the progression of liver disease. We analyzed data from a prospective trial of ultrasound screening for hepatocellular carcinoma in order to identify risk factors for, and the impact of PVT in patients with cirrhosis.Methods: 1243 adults with cirrhosis without PVT were enrolled from 43 liver units in France and Belgium, between June 2000 and March 2006. Mean follow-up was 47 months. Doppler ultrasonography was used to check portal vein. Progression of liver disease was defined by the development of: ascites, hepatic encephalopathy, variceal bleeding, prothrombin <45%, serum bilirubin >45 μmol/L, albumin <28 g/L, and/or creatinine >115 μmol/L. G20210A prothrombin and factor V gene mutations were assessed in sera stored in 3 large centers.Results: Five-year cumulative incidence of PVT was 10.7%. PVT was mostly partial and varied over time. The development of PVT was independently associated with baseline esophageal varices (P = 0.01) and prothrombin time (P = 0.002), but not with disease progression before PVT, or prothrombotic mutations. Disease progression was independently associated with baseline age (HR 1.55; 95%CI 1.11-2.17), body mass index (HR 1.40; 95%CI 1.01-1.95), prothrombin time (HR 0.79; 95%CI 0.70-0.90), serum albumin (HR 0.97; 95%CI 0.94-0.99), and esophageal varices (HR 1.70; 95%CI 1.21-2.38) but not with the prior development of PVT (HR 1.32; 95%CI 0.68-2.65).Conclusions: In patients with cirrhosis, the development of PVT is associated with the severity of liver disease at baseline, but does not follow a recent progression of liver disease. There is no evidence that the development of PVT is responsible for further progression of liver disease. (Hepatology 2014;)
    Hepatology 10/2014; · 12.00 Impact Factor
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    ABSTRACT: Background/aimsBehcet¿s disease (BD) is a well-known cause of Budd-Chiari syndrome (BCS). Data are lacking on the presentation and outcome of BCS related to BD.Methods We investigated the relationship between BD and BCS in 14 patients with both diseases and compared the results to 92 BCS patients without BD.ResultsMale gender (p¿=¿0.003), North African origin (P¿=¿0.007) and inferior vena cava obstruction (P <0.0001) were more frequent in patients with BD and BCS than in those with BCS alone and the plasma C-reactive protein level was higher (p¿=¿0.003). Two of the patients with the combined diseases underwent recanalization of the vena cava and the hepatic veins, none received transjugular intrahepatic portosystemic shunts (TIPS), one received a surgical shunt and one underwent liver transplantation. TIPS were less frequent in patients with BD and BCS than in those with BCS alone (P¿=¿0.019). Eighty six per cent of patients with BCS and BD received corticosteroids and immunosuppressive therapy. The 5-year transplantation-free survival rate was 63% in patients with BCS alone and 91% in those without BD (P¿=¿0.11). In our series and in the literature, a high number of patients [12 (61.5%) and 11 (64.7%) respectively] treated with anticoagulation and corticosteroids and/or immunosuppressants did not require invasive treatment.Conclusion This study shows a higher frequency of IVC obstruction in patients with BCS and BD. Medical treatment with anticoagulation and immunosuppressive agents may improve the symptoms of BCS. Therefore early management with immunosuppressive and anticoagulation therapy appears to be the treatment of choice in patients with BCS and BD.
    Orphanet Journal of Rare Diseases 09/2014; 9(1):104. · 4.32 Impact Factor
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    ABSTRACT: Refractory ascites may appear in liver transplant recipients with recurrence of hepatitis C virus infection, even in the absence of advanced fibrosis. The mechanisms are unclear. The aim was to determine whether post-transplant cryoglobulinemia could be a predisposing factor for ascites in this population.Retrospective data of 82 liver transplant recipients with HCV recurrence surviving more than one year were collected. Cryoglobulinemia was systematically tested after transplantation. All patients had one year protocol biopsy with assessment of sinusoidal distension, perisinusoidal fibrosis and centrolobular necrosis. Additional biopsies were performed when needed.Fourteen out of 82 patients (17%) developed refractory ascites. When ascites appeared, fibrosis was stage F0-F1 in 36% and F2-F3 in 57%. Factors independently associated with post-transplant ascites were pre-transplant refractory ascites (p=0.001), fibrosis ≥ stage 2 at one year (p=0.002), perisinusoidal fibrosis at one year (p=0.02) and positive cryoglobulinemia (p=0.02). Patients with ascites had a significantly worse prognosis compared to those without ascites.Refractory ascites may occur in liver transplant recipients with HCV recurrence in the absence of advanced fibrosis. The finding that both positive cryoglobulinemia and perisinusoidal fibrosis at one year were significantly associated with ascites suggests that liver microangiopathy is involved in the mechanisms of HCV-related ascites.This article is protected by copyright. All rights reserved.
    Transplant International 09/2014; · 3.16 Impact Factor
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    Journal of Hepatology 09/2014; · 9.86 Impact Factor
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    ABSTRACT: SUMMARY This study aimed to assess and compare the epidemiology of faecal carriage of extended spectrum β-lactamase-producing enterobacteria (ESBL-E) in Hepatology departments of two hospitals specializing in liver diseases, Theodor Bilharz Research Institute (TBRI) in Cairo (Egypt) and Beaujon Hospital (Bj) in Clichy (France). CTX-M groups were identified by PCR, and TEM and SHV derivatives with the check-point system. Phylogenetic groups of E. coli were determined by multiplex PCR, and clone ST131 by PCR of gene pabB. Prevalence of ESBL-E was 77·6% (45/58) in TBRI and 6·5% (13/199) in Bj (P < 10-7). Previous hospitalization was more common (P = 0·003) in Bj patients (93%) than in TBRI patients (45%) suggesting high prevalence of ESBL-E in the Egyptian community. The presence of E. coli B2 ST131 among ESBL-E faecal E. coli in Egypt confirms its pervasiveness in the community and raises concern regarding this highly virulent and resistant clone.
    Epidemiology and infection. 07/2014;
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    ABSTRACT: In patients with chronic hepatitis C (CHC), cirrhosis is associated with age, gender, diabetes, alcohol abuse and coinfection with human immunodeficiency virus (HIV) or hepatitis B virus (HBV). The impact of these factors on the outcome of cirrhosis is unknown. This study in CHC patients with cirrhosis aimed to assess the influence of these factors on decompensation, liver transplantation and death. Consecutive patients with CHC and cirrhosis hospitalized between January 1st 2006 and December 31st 2008 were followed-up until death, transplantation or study closure in March 2013. Gender, age, MELD score, diabetes, alcohol abuse, HIV or HBV coinfection were collected at inclusion. The complications of cirrhosis, death and liver transplantation were recorded at inclusion and during follow-up. The association between baseline factors and liver-related outcomes at inclusion and during follow-up were tested using logistic regression and Cox model, respectively. 348 patients with CHC and cirrhosis (68% men, median age 59 years, median MELD 10) were included. At baseline, 29% of the patients had diabetes, 6% alcohol abuse and 6% HIV or HBV coinfection. Baseline MELD ≥10 (p < 0.001), diabetes (p = 0.03) and HBV coinfection (p = 0.001) were independently associated with transplantation-free survival. Baseline diabetes was independently associated with ascites (p = 0.05), bacterial infections (p = 0.001) and encephalopathy (p < 0.001) at inclusion. Baseline diabetes was independently associated with the development of ascites (p = 0.057), renal dysfunction (p = 0.004), bacterial infections (p = 0.007) and hepatocellular carcinoma (p = 0.016) during the follow-up. Conclusion: In patients with CHC and cirrhosis, diabetes is an independent prognostic factor. Improving diabetes control may improve the outcome of cirrhosis. (Hepatology 2014)
    Hepatology 05/2014; · 12.00 Impact Factor
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    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
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    ABSTRACT: Waiting-list mortality in patients with cirrhosis and a relatively low MELD score is a matter of concern. The aim of this study was to determine whether a marker of muscle waste could improve prognostication. A pre-MELD cohort (waiting time-based allocation; n=186) and a MELD-era cohort (n=376) were examined. At evaluation, transversal psoas muscle thickness (TPMT) was measured on a computed tomography (CT) image at the level of the umbilicus. In the pre-MELD cohort, TPMT/height (mm/m) and the MELD score were entered in univariate and multivariate models to predict mortality after registration. Applicability of pre-MELD findings was tested in the MELD-era. In the pre-MELD cohort, the MELD score and TPMT/height were significantly associated with mortality. The discrimination of a score combining MELD and TPMT/height (MELD-psoas) was of 0.84 (95%CI: 0.62-0.95). In the MELD-era, TPTM/height was significantly associated with mortality, independent of the MELD and MELD-Na scores. There was a 15% increase in mortality risk per unit decrease in TPMT/height. The discrimination of MELD-psoas score (0.82; 95%CI 0.64-0.93) was superior to that of the MELD score and similar to that of the MELD-Na score. In patients with refractory ascites, mortality was significantly higher when TPMT/height was < 16.8 mm/m (42% versus 9%, p=0.02). TPMP/height on CT at the level of the umbilicus, an objective marker of muscle waste, may be predictive of mortality in cirrhotic patients, independent of the MELD and MELD-Na scores. It may help better assess the prognosis of patients with refractory ascites.
    Journal of Hepatology 03/2014; · 9.86 Impact Factor
  • Edna Strauss, Dominique Valla
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    ABSTRACT: Non-cirrhotic portal hypertension (NCPH) is mainly related to vascular disorders in the portal system, granuloma formation with periportal fibrosis or genetic alterations affecting the hepatobiliary system. For the diagnosis of the so-called idiopathic NCPH, it is essential to rule out chronic liver diseases associated with progression to cirrhosis as viral hepatitis B and C, alcoholic and non-alcoholic fatty liver, autoimmune disease, hereditary hemochromatosis, Wilson's disease as well as primary biliary cirrhosis and primary sclerosing cholagitis. This mini review will focus on the most common types of NCPH, excluding the idiopathic NCPH. Primary Budd-Chiari syndrome, characterized by obstruction of hepatic venous outflow, must be distinguished from sinusoidal obstruction syndrome, a cause of portal hypertension associated with exposure to toxic plants or therapeutic agents. Noninvasive imaging methods usually help the diagnosis of both Budd-Chiari syndrome and portal thrombosis, the later a relatively frequent cause NCPH. Clinical presentation and management of these vascular disorders are evaluated. Schistosomiasis, a worldwide spread endemic parasitic disease, may evolve to severe forms of the disease with huge spleen and gastroesophageal varices due to presinusoidal portal hypertension. Although management of acute upper gastrointestinal bleeding is similar to that of cirrhosis, prevention of rebleeding differs. Instead of portosystemic shunt procedures, the esophagogastric devascularization with splenectomy is the accepted surgical alternative. Its association with endoscopic therapy is suggested to be the best option for PH due to schistosomiasis. In conclusion, the prompt diagnosis of the disorder leading to non-cirrhotic portal hypertension is essential for its correct management.
    Gastroentérologie Clinique et Biologique 02/2014; · 0.80 Impact Factor
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    ABSTRACT: Microvesicles (MVs) are extracellular vesicles released by virtually all cells, under both physiological and pathological conditions. They contain lipids, proteins, RNAs and microRNAs and act as vectors of information that regulate the function of target cells. This Review provides an overview of the studies assessing circulating MV levels in patients with liver diseases, together with an insight into the mechanisms that could account for these changes. We also present a detailed analysis of the implication of MVs in key processes of liver diseases. MVs have a dual role in fibrosis as certain types of MVs promote fibrolysis by increasing expression of matrix metalloproteinases, whereas others promote fibrosis by stimulating processes such as angiogenesis. MVs probably enhance portal hypertension by contributing to intrahepatic vasoconstriction, splanchnic vasodilation and angiogenesis. As MVs can modulate vascular permeability, vascular tone and angiogenesis, they might contribute to several complications of cirrhosis including hepatic encephalopathy, hepatopulmonary syndrome and hepatorenal syndrome. Several results also suggest that MVs have a role in hepatocellular carcinoma. Although MVs represent promising biomarkers in patients with liver disease, methods of isolation and subsequent analysis must be standardized.
    Nature Reviews Gastroenterology &#38 Hepatology 02/2014; · 10.43 Impact Factor
  • Dominique C. Valla
    Journal of Clinical and Experimental Hepatology. 02/2014; 4:S1.
  • The American Journal of Gastroenterology 12/2013; 108(12):1937-8. · 9.21 Impact Factor
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    ABSTRACT: The most serious complication of acute mesenteric vein thrombosis (MVT) is acute intestinal ischemia requiring intestinal resection or causing death. Risk factors for this complication are unknown. to identify risk factors for severe intestinal ischemia leading to intestinal resection in patients with acute MVT. We retrospectively analysed consecutive patients seen between 2002 and 2012 with acute MVT in 2 specialized units. Patients with cirrhosis were excluded. We compared patients who required intestinal resection to patients who did not. Among 57 patients, a local risk factor was identified in 14 (24%) patients, oral contraceptive use in 16 (29%), and at least one or more other systemic pro-thrombotic condition in 25 (44%). Five (9%) patients had diabetes mellitus (DM), 33 (58%) had overweight or obesity, 9 (18%) had hypertriglyceridemia, 10 (19%) had arterial hypertension. Eleven patients (19%) underwent intestinal resection. DM was significantly associated with intestinal resection (p=0.02) while local factors or pro-thrombotic conditions were not. Computed tomography (CT) scans performed at diagnosis found that occlusion of second order radicles of the superior mesenteric vein was more frequently observed in patients who underwent intestinal resection (p=0.009). n acute MVT, patients with underlying DM have an increased risk of requiring intestinal resection. Neither local factors nor systemic pro-thrombotic conditions are associated to intestinal resection. When CT scan shows the preservation of second order radicles of the superior mesenteric vein, the risk of severe resection is low. This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 11/2013; · 3.87 Impact Factor
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    ABSTRACT: Simultaneous liver and kidney transplantation (SLKT) remains the procedure of choice for patients with both end stage liver disease and kidney failure. Stringent guidelines are needed to avoid unnecessary kidney transplantation. A recent consensus meeting proposed criteria based on Modified Diet in Renal (MDRD)-6 equation to estimate glomerular filtration rate (GFR). The aims of this study were to compare GFR equations to true GFR in candidates for liver transplantation (LT) and to determine the impact of inaccuracies on the current guidelines for SLKT. Three hundred stable cirrhotic patients evaluated for LT were studied. All patients had iohexol clearance to measure GFR at evaluation under stable condition. Measured GFR (mGFR) was compared to MDRD-4, MDRD-6 and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. MDRD-6 was the most accurate equation to predict GFR. In the 290 patients with mGFR >30 mL/min/1.73m(2) , 15 patients (7%) had eGFR ≤40 mL/min/1.73m(2) based on the MDRD-6 equation, defining "discordant" patients. Among them, 2 underwent SLKT and 13 underwent LT alone. None of those who survived more than one year after LT alone (n=8) developed renal dysfunction thereafter. In multivariate analysis, discordant patients were older (p=0.03) and had lower sodium level (p=0.02). Conclusions: MDRD-6 equation was superior to other equations at identifying cirrhotic patients with true GFR <30 mL/min/1.73m(2) . However, MDRD-6 equation also tended to overestimate renal function in a subgroup of patients with true GFR >30 mL/min/1.73m(2) , with a potential risk of unnecessary kidney transplantation if applying current US recommendations for SLKT. (Hepatology 2013;).
    Hepatology 08/2013; · 12.00 Impact Factor
  • Journal of Hepatology 06/2013; · 9.86 Impact Factor
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    ABSTRACT: AIM: To evaluate the diagnosis and presentation of liver tumours in patients with congenital portosystemic shunts (CPS). MATERIALS AND METHODS: Eight patients were diagnosed in Hôpital Beaujon as having CPS. All patients underwent Doppler ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and histological examination of liver tumours. CPS were classified according to anatomy and the amount of portal flow deviated to the systemic circulation as: total, subtotal, or partial. Liver tumours were diagnosed by needle core biopsy (n = 5) or surgery (n = 3). Clinical follow-up was available in all patients but one (mean follow-up 36 months; range 1-5 years). RESULTS: Six patients had total CPS, one patient had a subtotal CPS, and the last had a partial CPS. All patients presented with multiple liver nodules (range four to >15). The tumours were characterized as focal nodular hyperplasia (FNH; n = 4), FNH with hepatocellular adenoma (n = 2), and regenerative nodular hyperplasia (n = 2). In four of seven patients (57%) that had follow-up, tumours showed enlargement or new lesions appeared. CONCLUSION: In this series of CPS patients, tumours were all benign, multiple, and of hepatocellular origin, and different tumours were present simultaneously in two patients. Tumour enlargement or new nodules were common during follow-up.
    Clinical Radiology 03/2013; · 1.66 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Lipopolysaccharide (LPS)-expressing bacteria cause severe inflammation in cirrhotic patients. The global gene response to LPS is unknown in cirrhotic immune cells. METHODS: Gene-expression profiling using Affymetrix Human Exon Array analyzed the expression of 14,851 genes in LPS-stimulated peripheral blood mononuclear cells (PBMCs) from 4 patients with cirrhosis and 4 healthy subjects. We performed validation studies using RT-qPCR in LPS-simulated PBMCs from 57 patients and 9 healthy subjects and investigated the association of gene induction with mortality in 26 patients. RESULTS: Gene-expression profiling of LPS-stimulated cirrhotic cells showed 509 upregulated genes and 1,588 downregulated genes. In LPS-stimulated "healthy" cells, 952 genes were upregulated and 838 genes downregulated. The 741 LPS-regulated genes shared by cirrhotic and "healthy" cells were involved in cytokine production/activity and the induction of "immune paralysis". Comparison of functions associated with the 1,356 genes that were specifically regulated by LPS in cirrhotic cells to functions of the 1,049 genes specifically regulated in "healthy "cells allowed to define a cirrhosis-specific phenotype. Unlike in "healthy" cells, LPS failed to induce an interferon-mediated program in cirrhotic cells. In cirrhotic PBMCs, LPS specifically induced certain molecules involved in apoptosis and downregulated molecules involved in endocytic trafficking. RT-qPCR experiments showed that LPS-stimulated cirrhotic PBMCs had an enhanced induction of certain proinflammatory cytokines and chemokines. In the prognosis study, higher ex-vivo LPS-induction of inflammatory genes IL6 and CXCL5 were significant predictors of mortality. CONCLUSIONS: Our results show that LPS-stimulated cirrhotic PBMCs exhibit an extensive and often unexpected transcriptional response.
    Journal of Hepatology 01/2013; · 9.86 Impact Factor
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    ABSTRACT: To study the efficacy and factors associated with a sustained virological response (SVR) in chronic hepatitis C (CHC) relapsing patients. Out of 1228 CHC patients treated with pegylated interferon (PEG-IFN) and ribavirin (RBV), 165 (13%) had a relapse. Among these, 62 patients were retreated with PEG-IFN-α2a or -α2b and RBV. Clinical, biological, virological and histological data were collected. Initial doses and treatment modifications were recorded. The efficacy of retreatment and predictive factors for SVR were analyzed. An SVR was achieved in 42% of patients. SVR was higher in young (< 50 years) (61%) than old patients (27%) (P = 0.007), and in genotype 2 or 3 (57%) than in genotype 1 or 4 (28%) patients (P = 0.023). Prolonging therapy for at least 24 wk more than the previous course was associated with higher SVR rates (53% vs 28%, P = 0.04). Also, a better SVR rate was observed with RBV dose/body weight > 15.2 mg/kg per day (70% vs 35%, P = 0.04). In logistic regression, predictors of a response were age (P = 0.018), genotype (P = 0.048) and initial RBV dose/body weight (P = 0.022). None of the patients without a complete early virological response achieved an SVR (negative predictive value = 100%). Retreatment with PEG-IFN/RBV is eff-ective in genotype 2 or 3 relapsers, especially in young patients. A high dose of RBV seems to be important for the retreatment response.
    World Journal of Gastroenterology 06/2012; 18(23):2966-72. · 2.55 Impact Factor

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8k Citations
2,130.64 Total Impact Points


  • 2005–2014
    • Paris Diderot University
      • Centre de recherche biomédicale Bichat, Beaujon (CRB3) UMR-S 773
      Lutetia Parisorum, Île-de-France, France
    • Hôtel-Dieu de Paris – Hôpitaux universitaires Paris Centre
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Cliniques Universitaires Saint-Luc
      Bruxelles, Brussels Capital Region, Belgium
  • 2000–2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Duke University Medical Center
      • Department of Radiology
      Durham, NC, United States
    • National and Kapodistrian University of Athens
      • Division of Hygiene - Epidemiology
      Athens, Attiki, Greece
  • 2009–2011
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2008–2011
    • Hôpital Beaujon – Hôpitaux Universitaires Paris Nord Val de Seine
      Clicy, Île-de-France, France
    • Hôpital Saint-Louis (Hôpitaux Universitaires Saint-Louis, Laboisière, Fernand-Widal)
      Lutetia Parisorum, Île-de-France, France
  • 2000–2011
    • French Institute of Health and Medical Research
      • Centre de Recherche Biomédicale Bichat-Beaujon U773
      Lutetia Parisorum, Île-de-France, France
  • 1999–2008
    • University of Angers
      Angers, Pays de la Loire, France
  • 2002
    • ANRS - Agence Nationale de Recherche sur le Sida et les hépatites virales
      Lutetia Parisorum, Île-de-France, France
  • 1990–2002
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service d’Hépato - Gastro - Entérologie
      Lutetia Parisorum, Île-de-France, France
  • 2001
    • Centre hospitalier Laennec de Creil
      Creil, Picardie, France
  • 1998
    • Institut Arnault Tzanck
      Saint-Laurent, Provence-Alpes-Côte d'Azur, France