Dominique Valla

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

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Publications (129)803.26 Total impact

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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
  • Journal of Hepatology. 01/2014;
  • Dominique C. Valla
    Journal of Clinical and Experimental Hepatology. 01/2014; 4:S1.
  • The American Journal of Gastroenterology 12/2013; 108(12):1937-8. · 7.55 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: 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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    ABSTRACT: The MELDNa score was developed to improve the prognostic value of the MELD score in cirrhosis and was built for serum sodium concentrations numerically capped between 125 and 140 mmol/L. This model is not validated in a well-defined population of patients with cirrhosis and refractory ascites in whom severe hyponatremia (≤ 125 mmol/L) is frequent. This study assessed the prognostic value of severe hyponatremia and the MELDNa score in these patients. A consecutive, single-centre, observational, prospective study was performed in patients with cirrhosis and refractory ascites defined according to the International Ascites Club criteria. The prevalence of low serum sodium was assessed in this population. Predictive factors of mortality were analyzed and compared. One hundred seventy-four patients were included. Sixty-six (37.9%) had low serum sodium (< 130 mmol/L). Sixty-one (35.1%) had diuretic-intractable ascites due to severe hyponatremia (≤ 125 mmol/L). The median MELDNa score was 23 (10-33). The 1-year cumulative incidence of death was 55% (95% CI: 55-56%). The best predictive factors of mortality were the following: severe hyponatremia (≤ 125 mmol/L) as an underlying cause of refractory ascites, a higher Child-Pugh score, beta-blocker therapy, and a high frequency of large-volume paracentesis. The Child-Pugh score had a higher area under receiver operating curve to predict mortality than MELDNa. In patients with cirrhosis and refractory ascites, severe hyponatremia and Child-Pugh score are better predictors of mortality than MELDNa.
    Journal of Hepatology 04/2012; 57(2):274-80. · 9.86 Impact Factor
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    ABSTRACT: Circulating membrane-shed microparticles (MPs) participate in regulation of vascular tone. We investigated the cellular origins of MPs in plasma from patients with cirrhosis and assessed the contribution of MPs to arterial vasodilation, a mechanism that contributes to portal hypertension. We analyzed MPs from blood samples of 91 patients with cirrhosis and 30 healthy individuals (controls) using flow cytometry; their effects on the vascular response to vasoconstrictors were examined in vitro and in vivo. Circulating levels of leuko-endothelial (CD31(+)/41(-)), pan-leukocyte (CD11a(+)), lymphocyte (CD4(+)), and erythrocyte (CD235a(+)) MPs were higher in patients with cirrhosis than in controls. Plasma of patients with cirrhosis contained hepatocyte-derived MPs (cytokeratin-18(+)), whereas plasma from controls did not. The severity of cirrhosis and systemic inflammation were major determinants of the levels of leuko-endothelial and hepatocyte MPs. MPs from patients with advanced cirrhosis significantly impaired contraction of vessels in response to phenylephrine, whereas MPs from healthy controls or from patients of Child-Pugh class A did not. This effect depended on cyclooxygenase type 1 and required phosphatidylserine on the surface of MPs. Intravenous injection of MPs from patients with cirrhosis into BALB/C mice decreased mean arterial blood pressure. Cirrhosis is associated with increases in circulating subpopulations of MPs, likely resulting from systemic inflammation and liver cell damage. The overall pool of circulating MPs from patients with advanced cirrhosis impairs vasoconstrictor responses and decreases blood pressure, contributing to the arterial vasodilation associated with portal hypertension.
    Gastroenterology 03/2012; 143(1):166-76.e6. · 12.82 Impact Factor
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    Claire Francoz, Dominique Valla, François Durand
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    ABSTRACT: Portal vein thrombosis is not uncommon in candidates for transplantation. Partial thrombosis is more common than complete thrombosis. Despite careful screening at evaluation, a number of patients are still found with previously unrecognized thrombosis per-operatively. The objective is to recanalize the portal vein or, if recanalization is not achievable, to prevent the extension of the thrombus so that a splanchnic vein can be used as the inflow vessel to restore physiological blood flow to the allograft. Anticoagulation during waiting time and transjugular intrahepatic portosystemic shunt (TIPS) are two options to achieve these goals. TIPS may achieve recanalization in patients with complete portal vein thrombosis. However, a marked impairment in liver function, which is a characteristic feature of most candidates for transplantation, may be a contraindication for TIPS. Importantly, the MELD score is artificially increased by the administration of vitamin K antagonists due to prolonged INR. When patency of the portal vein and/or superior mesenteric vein is not achieved, only non-anatomical techniques (renoportal anastomosis or cavoportal hemitransposition) can be performed. These techniques, which do not fully reverse portal hypertension, are associated with higher morbidity and mortality risks. Multivisceral transplantation including the liver and small bowel needs to be evaluated. In the absence of prothrombotic states that may persist after transplantation, there is no evidence that pre-transplant portal vein thrombosis justifies long term anticoagulation post-transplantation, provided portal flow has been restored through conventional end-to-end portal anastomosis.
    Journal of Hepatology 03/2012; 57(1):203-12. · 9.86 Impact Factor
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    ABSTRACT: Polymorphisms in the region of the interleukin (IL)28B gene have been associated with pegylated-interferon (PEG-IFN) and ribavirin treatment response mainly in genotype 1 HCV infections. However, there are few data on HCV genotype 4 (HCV-4) infection. We evaluated, in a unique well-characterized cohort of HCV-4 patients, the association of IL28B polymorphism with response to treatment or liver disease severity. This study included 164 HCV-4 patients from different ethnic groups (Egyptian, European, and Sub-Saharan African). Among these patients, 82 were studied for response and 160 for disease severity. Free DNA extracted from all the 164 patient's serum samples was analyzed by direct sequencing of the SNP rs12979860 of IL28B. Genetic and bio-clinical features from patients having sustained virological response (43 SVR patients) and from those who did not respond to treatment or had a relapse after the end of the treatment (39 NR patients) were compared. IL28B polymorphism was compared between the 78 patients with mild fibrosis (Metavir score F0-F1) and the 82 with advanced fibrosis (F2-F4). Our data showed a better treatment response rate of the C allele of the IL28B gene SNP rs12979860 (p=0.0008). The response rates were 81.8%, 46.5%, and 29.4% for genotype CC, CT, and TT, respectively. No significant relationship was found between rs12979860 and the severity of the disease. The SNP rs12979860 is strongly associated with SVR in patients infected with HCV-4, but not with liver disease severity. Analysis of IL28B genotype might be used to guide treatment for these patients.
    Journal of Hepatology 09/2011; 56(3):527-32. · 9.86 Impact Factor
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    ABSTRACT: To retrospectively investigate the prevalence, MR findings, natural history, and association with other hepatic lesions of focal nodular hyperplasia (FNH)-like lesions in a cohort of consecutive patients with cavernous transformation of the portal vein (CTPV). This retrospective IRB-approved study comprised 58 patients (32 men, 26 women; average age, 50 years) with CTPV who underwent liver MR imaging between 2000 and 2008. MR images were assessed by two radiologists in consensus for the presence of (a) FNH-like lesions and other liver lesions, and (b) other imaging findings. Patients were assigned to a stable or progressive clinical course based on lesion characteristics at follow-up. Twelve of 58 patients (21%) had 38 FNH-like lesions (average size, 1.3 cm). Common findings of FNH-like lesions were isointensity on T2-weighted images (82%), intense and homogeneous enhancement during the arterial phase, and lack of washout during the hepatic venous and interstitial phases (100%). FNH-like lesions were found with other benign liver lesions (1 hemangioma, 1 adenoma) in two patients. Three (25%) patients with FNH-like lesions showed a progressive clinical course. FNH-like lesions are commonly detected in patients with CTPV. Most lesions demonstrate benign imaging findings and stable clinical course.
    European Radiology 06/2011; 21(10):2074-82. · 4.34 Impact Factor
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    ABSTRACT: Model for End-Stage Liver Disease (MELD) score-based allocation systems have been adopted by most countries in Europe and North America. Indeed, the MELD score is a robust marker of early mortality for patients with cirrhosis. Except for extreme values, high pretransplant MELD scores do not significantly affect posttransplant survival. The MELD score can be used to optimize the allocation of allografts according to a sickest first policy. Most often, patients with small hepatocellular carcinomas (HCCs) and low MELD scores receive extra points, which allow them appropriate access to transplantation comparable to the access of patients with advanced cirrhosis and high MELD scores. In addition to patients with advanced cirrhosis and HCC, patients with a number of relatively uncommon conditions have low MELD scores and a poor prognosis in the short term without transplantation but derive excellent benefits from transplantation. These conditions, which correspond to the so-called MELD score exceptions, justify the allocation of a specific score for appropriate access to transplantation. Here we report the conclusions of the French consensus meeting. The goals of this meeting were (1) to identify which conditions merit MELD score exceptions, (2) to list the criteria needed for defining each of these conditions, and (3) to define a reasonable time interval for organ allocation for each MELD exception in the general context of organ shortages. MELD exceptions were discussed in an attempt to reconcile the concepts of transparency, equity, justice, and utility.
    Liver Transplantation 06/2011; 17(10):1137-51. · 3.94 Impact Factor
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    ABSTRACT: Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients. Fifty-six CHC patients and 47 control patients (8 with nonalcoholic steatohepatitis or alcoholic liver disease, 18 with chronic heptatitis B virus infection, and 21 with no or mild liver abnormalities at histological examination) were included. Autophagy was assessed by means of electron microscopy and microtubule-associated protein light chain 3 immunoblotting. Using light chain 3 immunoblotting, the form present on autophagic vesicle (light chain 3-II) was significantly higher in CHC patients than in controls (P < 0.05). Using quantitative electron microscopy analysis, the median number of autophagic vesicles observed in hepatocytes from CHC patients was sixfold higher than in overall controls (P < 0.001). In contrast, there was no difference between CHC patients and controls in the number of mature lysosomes with electron-dense contents arguing in favor of a lack of fusion between autophagosome and lysosome. Neither genotype nor viral load influenced the autophagy level. In conclusion, autophagy is altered in hepatocytes from CHC patients, likely due to a blockade of the last step of the autophagic process.
    American Journal Of Pathology 06/2011; 178(6):2708-15. · 4.60 Impact Factor

Publication Stats

3k Citations
803.26 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
  • 2006–2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Duke University Medical Center
      • Department of Radiology
      Durham, NC, United States
  • 2010–2011
    • Unité Inserm U1077
      Caen, Lower Normandy, France
    • French Institute of Health and Medical Research
      • Centre de Recherche Biomédicale Bichat-Beaujon U773
      Paris, Ile-de-France, 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
  • 2007
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1993
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service d’Hépato - Gastro - Entérologie
      Lutetia Parisorum, Île-de-France, France