Richard Moreau

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

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Publications (382)2846.95 Total impact

  • Journal of Hepatology 09/2015; 63(3):537-9. DOI:10.1016/j.jhep.2015.07.003 · 10.40 Impact Factor
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    ABSTRACT: The peripheral arterial vasodilation hypothesis has been most influential in the field of cirrhosis and its complications. It has spawned hundreds of pathophysiogical studies in experimental and human cirrhosis and is the theoretical basis of life-saving treatments. It is undisputed that splanchnic arterial vasodilation contributes to portal hypertension and is the basis for manifestations such as ascites and hepatorenal syndrome, but the body of research generated by the hypothesis has revealed gaps in the original pathophysiological interpretation of these complications. The expansion of our knowledge on the mechanisms regulating vascular tone, inflammation and the host-microbiota interaction require a broader approach to advanced cirrhosis encompassing the whole spectrum of its manifestations. Indeed, multi-organ dysfunction and failure likely result from a complex interplay where the systemic spread of bacterial products represents the primary event. The consequent activation of the host innate immune response triggers endothelial molecular mechanisms responsible for arterial vasodilation, and also jeopardizes organ integrity with a storm of pro-inflammatory cytokines and reactive oxygen and nitrogen species. Thus, the picture of advanced cirrhosis could be seen as the result of an inflammatory syndrome in contradiction with a simple hemodynamic disturbance. Copyright © 2015. Published by Elsevier B.V.
    Journal of Hepatology 07/2015; DOI:10.1016/j.jhep.2015.07.004 · 10.40 Impact Factor
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    ABSTRACT: TARGETING TOLL-LIKE RECEPTOR 7 IN CHRONIC HBV INFECTION: Toll-like receptor (TLR) signaling has been implicated to play a significant role in the context of cytokine-induced 'curing' of HBV-infected cells. In previous studies, the oral small molecule TLR7 agonist GS-9620 caused a marked HBsAg reduction in chronically HBV-infected chimpanzees. The present study by Menne et al. evaluated GS-9620 in the HBV Woodchuck animal model demonstrating that short duration treatment with the TLR7 agonist was able to induce a sustained antiviral response which is likely due to the induction of local interferon-alpha and natural killer cell and CD8(+) T cell responses as well as activation of B cells. A striking reduction in the incidence of hepatocellular carcinoma was also observed in the treated animals. The safety and efficacy of GS-9620 (attaining a functional cure?) will be further developed in a phase II multi-center study in virally-suppressed subjects with chronic hepatitis B (ClinicalTrials.gov NCT02166047). Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
    Journal of Hepatology 06/2015; 62(6):1221-4. DOI:10.1016/j.jhep.2015.03.026 · 10.40 Impact Factor
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    Journal of Hepatology 05/2015; 62(5). DOI:10.1016/j.jhep.2015.02.032 · 10.40 Impact Factor
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    ABSTRACT: To determine the pathogenesis of liver nodules, and lesions similar to obliterative portal venopathy, observed after portosystemic shunts or portal vein thrombosis in humans. We conducted an experimental study comparing portacaval shunt (PCS), total portal vein ligation (PVL), and sham (S) operated rats. Each group were either sacrificed at 6 weeks (early) or 6 months (late). Arterial liver perfusion was studied in vivo using CT, and histopathological changes were noted. Liver mRNA levels were quantified by RT-QPCR for markers of inflammation (Il10, Tnfa), proliferation (Il6st, Mki67, Hgf, Hnf4a), angiogenesis: (Vegfa, Vegfr 1, 2 and 3; Pgf), oxidative stress (Nos2, and 3, Hif1a), and fibrosis (Tgfb). PCS and PVL were compared to the S group. Periportal fibrosis and arterial proliferation was observed in late PCS and PVL groups. CT imaging demonstrated increased arterial liver perfusion in the PCS group. RT-QPCR showed increased inflammatory markers in PCS and PVL early groups. Tnfa and Il10 were increased in PCS and PVL late groups respectively. All proliferative markers increased in the PCS, and Hnf4a in the PVL early groups. Mki67 and Hnf4a were increased in the PCS late group. Nos3 was increased in the early and late PCS groups, and Hif1a was decreased in the PVL groups. Markers of angiogenesis were all increased in the early PCS group, and Vegfr3 and Pgf in the late PCS group. Only Vegfr3 was increased in the PVL groups. Tgf was increased in the PCS groups. Portal deprivation in rats induces a sustained increase in intrahepatic markers of inflammation, angiogenesis, proliferation, and fibrosis.
    PLoS ONE 05/2015; 10(5):e0125493. DOI:10.1371/journal.pone.0125493 · 3.23 Impact Factor
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    ABSTRACT: The most efficient strategy to treat chronic liver disease including NAFLD is to remove the cause (i.e., hypocaloric diet and aerobic exercise in patients with NAFLD). Although aerobic exercise reduces liver fat and visceral adipose tissue, there are limited prospective studies assessing the effect of different exercise programs. The study from Keating et al. investigated the effects of different programs of aerobic exercise (low to moderate intensity, high volume vs. high intensity, low volume aerobic). The authors found that both aerobic exercise regimens reduced liver and visceral fat and VAT without significant weight loss. This important study supports that exercise should be advised, when possible, to patients with NAFLD. For patients unable to modify their lifestyle, targeted therapies are needed.
    Journal of Hepatology 04/2015; 63(1). DOI:10.1016/j.jhep.2015.04.014 · 10.40 Impact Factor
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    ABSTRACT: Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation of cirrhosis, organ failure(s) and high 28-day mortality. We investigated whether assessments of patients at specific time points predicted their need for liver transplantation (LT), or the potential futility of their care. We assessed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011, or during early (28-day) follow-up of the prospective multicenter European Chronic Liver Failure (CLIF) ACLF in Cirrhosis (CANONIC) study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. ACLF resolved or improved in 49.2%, had a steady or fluctuating course in 30.4% and worsened in 20.4%. The 28-day transplant-free mortality was low-moderate (6-18%) in patients with non-severe early course (final no ACLF or ACLF-1) and high-very high (42-92%) in patients with severe early course (final ACLF-2 or -3) independently of initial grades. Independent predictors of course severity were CLIF Consortium ACLF score - (CLIF-C ACLFs) and presence of liver failure (total bilirubin ≥ 12 mg/dL) at ACLF diagnosis. Eighty one percent had their final ACLF grade at 1 week, resulting in accurate prediction of short-(28-day) and mid-(90-day)term mortality by ACLF grade at 3-7 days. Among patients that underwent early LT, 75% survived for at least 1 year. Among patients with ≥4 organ failures, or CLIF-C ACLFs >64 at days 3 - 7 days, and did not undergo LT, mortality was 100% by 28 days Conclusions: The assessment of ACLF patients at 3-7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation due to futility. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases.
    Hepatology 04/2015; DOI:10.1002/hep.27849 · 11.19 Impact Factor
  • Richard Moreau
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    ABSTRACT: Patients with severe alcoholic hepatitis who are admitted to the hospital usually have evidence of decompensated cirrhosis with high serum bilirubin levels, low prothrombin time associated with dysfunction or failure of other organs/systems (kidney, brain, circulation).1 Spontaneous 1-month mortality is 35%.2 Pathophysiology of severe alcoholic hepatitis is incompletely understood.2-4 Alcohol consumption results in alterations of gut microbiome, increased intestinal permeability and subsequent translocation of Gram-negative bacteria. These bacteria may release pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS). In the liver, PAMPs stimulate Kupffer cells to produce high levels of proinflammatory chemokines (eg, interleukin-8 (IL-8)) or cytokines such as tumour necrosis factor α (TNF-α). TNF-α may activate cell death pathways and induce the production of reactive oxygen species (ROS) by hepatocyte mitochondria, leading to cell death. Acetaldehyde metabolism also contributes to hepatocyte ROS production. These findings led to the traditional view that excessive inflammation and oxidative stress are involved in the development of liver damage in patients with alcoholic hepatitis. Corticosteroid therapy (40 mg of oral prednisolone per day) is now considered as the first-line treatment for severe alcoholic hepatitis.2 However, according to the Lille model ∼40% of patients with severe alcoholic hepatitis do not respond to corticosteroids,2 and this group has high 6-month mortality (close to 80%).5 This is why novel, pathophysiology-based, medical therapies should be developed for patients who do not respond to corticosteroids. Dubuquoy et al6 provide new insights into the pathophysiology of severe alcoholic hepatitis. They investigated liver explants from patients with severe alcoholic hepatitis who underwent salvage transplantation, from patients with alcoholic cirrhosis and no alcoholic hepatitis and fragments of normal livers. … [Full text of this article]
    Gut 04/2015; DOI:10.1136/gutjnl-2015-309545 · 13.32 Impact Factor
  • Vicente Arroyo · Richard Moreau · Rajiv Jalan · Pere Ginès
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    ABSTRACT: Acute-on-chronic liver failure (ACLF) is a recently recognized syndrome characterized by acute decompensation (AD) of cirrhosis and organ/system failure(s) (organ failure: liver, kidney, brain, coagulation, circulation and/or respiration) and extremely poor survival (28-day mortality rate 30-40%). ACLF occurs in relatively young patients. It is especially frequent in alcoholic- and untreated hepatitis B associated-cirrhosis, in addition it is related to bacterial infections and active alcoholism, although in 40% of cases no precipitating event can be identified. It may develop at any time during the course of the disease in the patient (from compensated to long-standing cirrhosis). The development of ACLF occurs in the setting of a systemic inflammation, the severity of which correlates with the number of organ failures and mortality. Systemic inflammation may cause ACLF through complex mechanisms including an exaggerated inflammatory response and systemic oxidative stress to pathogen- or danger/damage-associated molecular patterns (immunopathology) and/or alteration of tissue homeostasis to inflammation caused either by the pathogen itself or through a dysfunction of tissue tolerance. A scoring system composed of three scores (CLIF-C OFs, CLIF-C AD, and CLIF-C ACLFs) specifically designed for patients with AD, with and without ACLF, allows a step-wise algorithm for a rational indication of therapy. The management of ACLF should be carried out in enhanced or intensive care units. Current therapeutic measures comprise the treatment for associated complications, organ failures support and liver transplantation. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
    Journal of Hepatology 04/2015; 62(1S):S131-S143. DOI:10.1016/j.jhep.2014.11.045 · 10.40 Impact Factor
  • Journal of Hepatology 04/2015; 62:S386. DOI:10.1016/S0168-8278(15)30432-3 · 10.40 Impact Factor
  • Journal of Hepatology 04/2015; 62:S373. DOI:10.1016/S0168-8278(15)30404-9 · 10.40 Impact Factor
  • Journal of Hepatology 03/2015; 62(3):503-504. DOI:10.1016/j.jhep.2015.06.011 · 10.40 Impact Factor
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    Journal of Hepatology 02/2015; DOI:10.1016/j.jhep.2015.02.012 · 10.40 Impact Factor
  • Richard Moreau · Emmanuel Weiss
    Hepatology 02/2015; 61(5). DOI:10.1002/hep.27762 · 11.19 Impact Factor
  • Thierry Gustot · Richard Moreau
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    ABSTRACT: Bacterial infection has become the leading cause of death in patients with cirrhosis. This susceptibility is explained by the paradoxical association of an immune defect in the clearance of bacteria and an overexpression of pro-inflammatory mediators responsible of sepsis-related organ failure. Bacterial infections must be suspected and screened for in all patients with decompensated cirrhosis. Spontaneous bacterial peritonitis (SBP) and urinary tract infection (UTI) are the most frequent types of infection followed by pneumonia, skin and soft tissue infection (SSTI), spontaneous bacteremia, and catheter-related infections. The prompt initiation of an adequate antibiotic therapy is the key to effective management. Broad use of long-term quinolones for prophylaxis and an increasing use of invasive procedures contributes to the development of multidrug-resistant bacteria. The choice of an adequate empiric antibiotic becomes a challenge, particularly in nosocomial infections. The administration of intravenous albumin can prevent the development of organ failure, at least in SBP. Sepsis-related organ failures are associated with a very poor outcome in cirrhotic patients. Multiple prophylactic strategies are effective in preventing bacterial infection in high-risk cirrhotic patients.
    Cirrhosis: A practical guide to management, 01/2015: pages 164-174; , ISBN: 9781118274828
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    Journal of Hepatology 01/2015; 23(4). DOI:10.1016/j.jhep.2014.12.029 · 10.40 Impact Factor
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    ABSTRACT: Acute renal failure (ARF) is a common complication in patients with decompensated cirrhosis. The traditional diagnostic criteria of renal failure in these patients were proposed in 19961 and have been refined in subsequent years.2 According to these criteria, ARF is defined as an increase in serum creatinine (sCr) of ≥50% from baseline to a final value >1.5 mg/dL (133 µmol/L). However, the threshold value of 1.5 mg/dL (133 µmol/L) sCr to define renal failure in patients with decompensated cirrhosis has been challenged.3 ,4 In addition, the timeframe to distinguish acute from chronic renal failure has not been clearly identified, the only exception being type 1 hepatorenal syndrome (HRS). Meanwhile, new definitions for ARF, now termed acute kidney injury (AKI), have been proposed and validated in patients without cirrhosis.5-7 Recently these new criteria were also proposed and applied in the diagnosis of AKI in patients with cirrhosis.3 ,8-15 Thus, in December 2012, the International Club of Ascites (ICA) organised a consensus development meeting in Venice, Italy, in order to reach a new definition of AKI in patients with cirrhosis. The discussion among the experts continued thereafter for 2 years, both online and through several meetings, between those experts who had different positions on crucial points on the subject. This paper reports the scientific evidence supporting the final proposal of a new approach to the diagnosis and treatment of this condition, on which the experts agreed.
    Gut 01/2015; 64(4). DOI:10.1136/gutjnl-2014-308874 · 13.32 Impact Factor
  • 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; 62(4). 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; 274(2):140313. DOI:10.1148/radiol.14140313 · 6.21 Impact Factor

Publication Stats

8k Citations
2,846.95 Total Impact Points

Institutions

  • 2009–2015
    • Paris Diderot University
      • Centre de recherche biomédicale Bichat, Beaujon (CRB3) UMR-S 773
      Lutetia Parisorum, Île-de-France, France
    • Université Libre de Bruxelles
      • Intensive Care Unit
      Bruxelles, Brussels Capital, Belgium
  • 1997–2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2013
    • Hôpital Beaujon – Hôpitaux Universitaires Paris Nord Val de Seine
      Clicy, Île-de-France, France
  • 2008–2013
    • University of Paris-Est
      La Haye-Descartes, Centre, 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 Paris-Saclay
      Lutetia Parisorum, Île-de-France, France
  • 2002
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2001
    • Hôpital Universitaire Robert Debré
      Lutetia Parisorum, Île-de-France, France
    • Centre Chirurgical Marie Lannelongue
      Plessis-Robinson, Île-de-France, France
  • 2000
    • University of Strasbourg
      Strasburg, Alsace, France
  • 1999
    • Hôpital Cochin (Hôpitaux Universitaires Paris Centre)
      Lutetia Parisorum, Île-de-France, France
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France