Richard Moreau

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

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Publications (354)2587.62 Total impact

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  • Gut 01/2015; DOI:10.1136/gutjnl-2014-308874 · 13.32 Impact Factor
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  • Richard Moreau
    Journal of Hepatology 12/2014; DOI:10.1016/j.jhep.2014.12.002 · 10.40 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; DOI:10.1016/j.jhep.2014.11.012 · 10.40 Impact Factor
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    ABSTRACT: Purpose To compare the value of enhancement and pharmacokinetic parameters measured at dynamic gadoxetate-enhanced magnetic resonance (MR) imaging in determining hepatic organic anion transporter expression in control rats and rats with advanced liver fibrosis. Materials and Methods Institutional animal review board approval was received before the study began. Advanced liver fibrosis was created in rats by means of carbon tetrachloride injections over an 8-week period. In 17 rats with liver fibrosis and eight control rats, dynamic gadoxetate-enhanced MR images of the liver were obtained during 1 hour after injection of 0.025 mmol gadoxetate per kilogram of body weight. Enhancement parameters (maximum enhancement [ Emax maximum enhancement ], time to peak [ Tmax time to peak ], and elimination half-life) were measured on enhancement-versus-time curves, and pharmacokinetic parameters (hepatic extraction fraction [ HEF hepatic extraction fraction ] and mean residence time [ MRT mean residence time ]) were obtained by means of deconvolution analysis of the concentration-versus-time curves in the liver and the portal vein. The parameters were correlated at simple and multiple regression analysis with the expression of the hepatic anion uptake transporter organic anion-transporting polypeptide 1A1 ( Oatp organic anion-transporting polypeptide 1a1), the hepatobiliary transporter multidrug resistance-associated protein 2 ( Mrp multidrug resistance-associated protein 2), and the backflux transporter Mrp multidrug resistance-associated protein 4, as determined with reverse transcription polymerase chain reaction. Results In rats with advanced liver fibrosis, the Emax maximum enhancement , Tmax time to peak , HEF hepatic extraction fraction , and MRT mean residence time decreased significantly relative to those in control rats, whereas the elimination half-life increased significantly. The enhancement and pharmacokinetic parameters correlated significantly with the expression of the transporters at simple regression analysis. At multiple regression analysis, HEF hepatic extraction fraction was the only parameter that was significantly associated with the expression of Oatp organic anion-transporting polypeptide 1a1 and Mrp multidrug resistance-associated protein 2 (P < .001, r = 0.74 and P < .001, r = 0.70, respectively). Conclusion The pharmacokinetic parameter HEF hepatic extraction fraction at dynamic gadoxetate-enhanced MR imaging is independently correlated with hepatic organic anion transporter expression. © RSNA, 2014.
    Radiology 10/2014; DOI:10.1148/radiol.14140313 · 6.21 Impact Factor
  • Richard Moreau, Rajiv Jalan, Vicente Arroyo
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    ABSTRACT: A proportion of patients hospitalized for an acute complication of cirrhosis are at high risk of short-term death. The term Acute-on-Chronic Liver Failure (ACLF) is used to characterize these patients. Until recently there was no evidence-based definition of ACLF. In 2013 a definition has been proposed based on results of a large prospective observational European study, called “European Association for the Study of the Liver (EASL)–Chronic Liver Failure (CLIF) Consortium Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC)” study. Results of this study led to elaborate new concepts about ACLF. First, it was found that ACLF is a syndrome that is distinct from mere decompensated cirrhosis. It was also shown that ACLF is a dynamic syndrome which can improve or conversely worsen. Patients who worsen die rapidly from multiorgan failures. The CANONIC study also found that identifiable precipitating events (e.g., bacterial infection, active alcoholism) are found in only 50% of cases of ACLF indicating that these events are dispensable for defining ACLF. In addition precipitating events may be initiators of ACLF but do not drive the outcome. An important concept derived from the CANONIC study is that ACLF is associated with systemic inflammation even in patients who do not have identifiable precipitating events. Finally it was found that ACLF may develop in patients without prior episodes of decompensation or in those with recent decompensation (<3 months). Moreover these patients with “early” ACLF were more severe than patients who developed ACLF after a long of history of decompensated cirrhosis.
    10/2014; DOI:10.1016/j.jceh.2014.09.003
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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 09/2014; 60(3). DOI:10.1002/hep.27228 · 11.19 Impact Factor
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    ABSTRACT: Portal hypertension has traditionally been viewed as a progressive process, involving ultrastructural changes including fibrosis, nodule formation and vascular thrombosis, leading to increased intrahepatic resistance to flow. However, it is increasingly recognized that a significant component of this vascular resistance results from a dynamic process, regulated by complex interactions between the injured hepatocyte, the sinusoidal endothelial cell, the Kupffer cell and the hepatic stellate cell, which impact on sinusoidal calibre. Recent findings suggest these haemodynamic findings are most marked in patients with superimposed inflammation. The precise mechanisms for vascular dysfunction in cirrhosis with superimposed inflammation remain to be fully elucidated but several studies over the past decade have started to generate the hypothesis that inflammation may be a key mediator of the pathogenesis and severity of portal hypertension in this context. This review provides a comprehensive overview of the biological mechanisms for inflammation playing a key role in the severity of portal hypertension, and illustrates potential novel therapies that act by modifying these processes.
    Journal of Hepatology 07/2014; DOI:10.1016/j.jhep.2014.03.014 · 9.86 Impact Factor
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    ABSTRACT: Abstract BACKGROUND & AIMS: Acute-on Chronic Liver Failure (ACLF) is a frequent syndrome (30% prevalence) characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality. This study develops and validates a specific prognostic score for ACLF patients. METHODS: Data from 1,349 patients included in the CANONIC study were used. First, a simplified organ function scoring system (CLIF-Consortium Organ Failure score, CLIF-C OFs) to diagnose ACLF was developed using data from all patients. Subsequently, in 275 patients with ACLF, CLIF-C OFs and two other independent predictors of mortality (age and white-cell count) were combined to develop a specific prognostic score for ACLF (CLIF CONSORTIUM score for ACLF, CLIF-C ACLFs). Concordance index (C-index) was used to compare the discrimination abilities of CLIF-C ACLFs, MELD (MELDs), MELD-Sodium (MELD-Nas) and Child-Pugh (CPs) scores. CLIF-C ACLFs was validated in an external cohort and assessed for sequential use. RESULTS: CLIF-C ACLFs showed a significantly higher predictive accuracy than MELDs, MELD-Nas and CPs, reducing (19-28%) the corresponding prediction error rates at all the main time-points after ACLF diagnosis (28, 90, 180 and 365 days) in both the CANONIC and the external validation cohort. CLIF-C ACLFs computed at 48 hours, 3-7 days and 8-15 days after ACLF diagnosis predicted 28-day mortality significantly better than at diagnosis. CONCLUSIONS: CLIF-C ACLFs at ACLF diagnosis is superior to MELDs and MELD-Nas in predicting mortality. CLIF-C ACLFs is a clinically relevant, validated scoring system that can be used sequentially to stratify the risk of mortality in ACLF patients.
    Journal of Hepatology 06/2014; 61(5). DOI:10.1016/j.jhep.2014.06.012. · 10.40 Impact Factor
  • Vicente Arroyo, Richard Moreau
    Nature medicine 05/2014; 20(5):467-9. DOI:10.1038/nm.3553 · 28.05 Impact Factor
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    ABSTRACT: Genetic polymorphisms modulate the expression of proinflammatory cytokines. We prospectively assessed the influence of 6 single nucleotide polymorphisms (SNPs) in TNFα, IL-6 and IL1β genes on the risk of hepatocellular carcinoma (HCC) in patients with cirrhosis. TNFα (G-238A, C-863A, G-308A), IL-6 (C-174G) and IL1β (C-31T,C-511T) SNPs were assessed in 232 alcoholics and 253 HCV-infected patients with biopsy-proven cirrhosis, prospectively followed up and screened for HCC. Their influence on HCC development was assessed using the Kaplan-Meier method. These variants did not influence the risk of HCC in alcoholic patients. Conversely, two variants influenced the risk of HCC occurrence in patients with HCV-related cirrhosis, namely the TNFα-308 (A) allele (HR=2.4 [1.6-3.7], log-rank<0.0001) and the IL1β-31 (T) allele (HR=1.5 [1.1-2.1], log-rank=0.004). When stratifying HCV-infected patients into four genotypic associations expected to progressively increase TNFα and IL1β production, we observed increasing risk of HCC occurrence (log-rank<0.0001) from group 1 to 4. The TNFα-308 (A) allele was the only genetic trait independently associated with risk of HCC in these patients, along with older age, male gender, BMI and platelet count. These variables led to construction of a predictive score able to separate patients with HCV-related cirrhosis into three subgroups with progressively increasing 5-year cumulative incidences of 4.7%, 14.1% and 36.3%, respectively (log-rank<0.0001). Genetic heterogeneity in the TNFα and IL1β gene promoters influences the risk of HCC in patients with HCV-induced cirrhosis. These genetic data, when incorporated into clinical scores, are able to refine selection of risk classes of HCC.
    Journal of Hepatology 04/2014; DOI:10.1016/j.jhep.2014.04.011 · 9.86 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 04/2014; 59(4). DOI:10.1002/hep.26704 · 11.19 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S239. DOI:10.1016/S0168-8278(14)60670-X · 10.40 Impact Factor
  • Journal of Hepatology 04/2014; 60(1):S30-S31. DOI:10.1016/S0168-8278(14)60076-3 · 10.40 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; DOI:10.1016/j.jhep.2014.02.026 · 9.86 Impact Factor
  • Richard Moreau
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    ABSTRACT: Decompensated cirrhosis is diagnosed by the presence of signs such as ascites, gastrointestinal hemorrhage, hepatic encephalopathy, bacterial infection or any combination of these (1). Ascites is the most common sign of decompensated cirrhosis (1). Ascites is primarily related to an inability to excrete an adequate amount of sodium into urine, leading to a positive sodium balance (2).This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 03/2014; 34(7). DOI:10.1111/liv.12545 · 4.41 Impact Factor
  • Richard Moreau, Vicente Arroyo
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    ABSTRACT: Patients hospitalized for an acute complication of cirrhosis who also have organ failure(s) are at high risk of short-term death. The term Acute-on-Chronic Liver Failure (ACLF) is used to characterize these patients. Until recently there was no evidence-based definition of ACLF. It is now the case because results of a large prospective observational European study called "chronic liver failure (CLIF) Acute-on-Chronic Liver Failure in Cirrhosis (CANONIC)" study have been published in 2013 establishing diagnostic criteria for ACLF in a large series of hospitalized patients who had an acute complication of cirrhosis. In addition, this study described the natural history of ACLF. According to the CANONIC study ACLF is now considered as a new clinical entity because it is distinct from "mere", traditional decompensated cirrhosis, based not only on the presence of organ failure(s) and high mortality rate but also on younger age, alcoholic etiology of cirrhosis, higher prevalence of some precipitating events (bacterial infections, active alcoholism), and higher level of systemic inflammation. ACLF is a new entity also because it cannot be entirely explained by severe sepsis or severe alcoholic hepatitis, a large proportion of cases being of "unknown" origin. ACLF should be considered as a whole that includes subcategories such as severe sepsis, severe alcoholic hepatitis and others which require to be defined. ACLF is a relatively common syndrome since it occurs in 31% of hospitalized patients with cirrhosis who have an acute complication of their liver disease. In these patients ACLF is the most common cause of death.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 02/2014; DOI:10.1016/j.cgh.2014.02.027 · 5.64 Impact Factor
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    ABSTRACT: Bacterial infections are very common and represent one of the most important reasons of progression of liver failure, development of liver-related complications, and mortality in patients with cirrhosis. In fact, bacterial infections may be a triggering factor for the occurrence of gastrointestinal bleeding, hypervolemic hyponatremia, hepatic encephalopathy, kidney failure, and development of acute-on-chronic liver failure. Moreover, infections are a very common cause of repeated hospitalizations, impaired health-related quality of life, and increased healthcare costs in cirrhosis. Bacterial infections develop as a consequence of immune dysfunction that occurs progressively during the course of cirrhosis. In a significant proportion of patients, infections are caused by gramnegative bacteria from intestinal origin, yet grampositive bacteria are a frequent cause of infection, particularly in hospitalized patients. In recent years, infections caused by multidrug-resistant bacteria are becoming an important clinical problem in many countries. The reduction of the negative clinical impact of infections in patients with cirrhosis may be achieved by a combination of prophylactic measures, such as administration of antibiotics, to reduce the occurrence of infections in high-risk groups together with early identification and management of infection once it has developed. Investigation on the mechanisms of altered gut microflora, translocation of bacteria, and immune dysfunction may help develop more effective and safe methods of prevention compared to those that are currently available. Moreover, research on biomarkers of early infection may be useful in early diagnosis and treatment of infections. The current manuscript reports and in-depth review and a position statement on bacterial infections in cirrhosis.
    Journal of Hepatology 02/2014; DOI:10.1016/j.jhep.2014.01.024 · 9.86 Impact Factor

Publication Stats

7k Citations
2,587.62 Total Impact Points


  • 2009–2015
    • Paris Diderot University
      • Centre de recherche biomédicale Bichat, Beaujon (CRB3) UMR-S 773
      Lutetia Parisorum, Île-de-France, France
  • 2014
    • Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
      Barcino, Catalonia, Spain
  • 2009–2014
    • University of Paris-Est
      La Haye-Descartes, Centre, France
  • 1988–2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2010–2012
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 1997–2012
    • French Institute of Health and Medical Research
      • Center of Biomedical Research Bichat-Beaujon
      Lutetia Parisorum, Île-de-France, France
  • 2011
    • Université de Montpellier 1
      Montpelhièr, Languedoc-Roussillon, France
  • 1999–2006
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Cochin (Hôpitaux Universitaires Paris Centre)
      Lutetia Parisorum, Île-de-France, France
  • 2001
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France