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1. Emotional overeating affected nine in ten female students during the COVID-19 university closure: A cross-sectional study in France

Author

Aymery Constant, Alexandra Fortier, Yann Serrand, Elise Bannier, Romain Moirand, Ronan Thibault, Nicolas Coquery, Ambre Godet, and David Val-Laillet

Subjects
Medicine, Science
Abstract

Objectives To estimate the proportion of female university students reporting overeating (EO) in response to emotions during the COVID-19 university closures, and to investigate social and psychological factors associated with this response to stress. Design Online survey gathered sociodemographic data, alcohol/drugs use disorders, boredom proneness and impulsivity using validated questionnaires, and EO using the Emotional Overeating Questionnaire (EOQ) assessing eating in response to six emotions (anxiety, sadness, loneliness, anger, fatigue, happiness), whose structure remains to be determined. Participants Sample of 302 female students from Rennes University, France. Main outcome measure Frequencies of emotional overeating. Analysis The frequency of emotional overeating was expressed for each emotion as percentages. Exploratory Factor analyses (EFA) were used to determine EOQ structure and provide an index of all EOQ items used for further analysis. Linear regression models were used to explore relationships between EO and others covariates. Results Nine in ten participants reported intermittent EO in the last 28 days, mostly during 6 to 12 days, in response to Anxiety (75.5%), Sadness (64.5%), Happiness (59.9%), Loneliness (57.9%), Tiredness (51.7%), and to a lesser extent to Anger (31.1%). EFA evidenced a one-factor latent variable reflecting “Distress-Induced Overeating” positively correlated with internal boredom proneness, tobacco use, attentional impulsivity, inability to resist emotional cues, and loss of control over food intake, and negatively with age and well-being. EO was unrelated to body mass index or substance abuse. Conclusion and implications Nine in ten female students reported emotional overeating during the COVID-19 university closure. This response to stress was related to eating tendencies typical of young women, but also to personality/behavioral patterns such as boredom and impulsivity proneness. Better understanding of the mechanisms underlying EO in response to stress and lack of external/social stimulation would improve preventive interventions.

Published
2023

3. Brain Responses to Food Choices and Decisions Depend on Individual Hedonic Profiles and Eating Habits in Healthy Young Women

Author

Nicolas Coquery, Yentl Gautier, Yann Serrand, Paul Meurice, Elise Bannier, Ronan Thibault, Aymery Constant, Romain Moirand, and David Val-Laillet

Subjects
eating behavior, decision-making, brain, healthy subjects, fMRI, rsfMRI, Nutrition. Foods and food supply, TX341-641
Abstract

The way different food consumption habits in healthy normal-weight individuals can shape their emotional and cognitive relationship with food and further disease susceptibility has been poorly investigated. Documenting the individual consumption of Western-type foods (i.e., high-calorie, sweet, fatty, and/or salty) in relation to psychological traits and brain responses to food-related situations can shed light on the early neurocognitive susceptibility to further diseases and disorders. We aimed to explore the relationship between eating habits, psychological components of eating, and brain responses as measured by blood oxygen level-dependent functional magnetic resonance imaging (fMRI) during a cognitive food choice task and using functional connectivity (FC) during resting-state fMRI (rsfMRI) in a population of 50 healthy normal-weight young women. A Food Consumption Frequency Questionnaire (FCFQ) was used to classify them on the basis of their eating habits and preferences by principal component analysis (PCA). Based on the PCA, we defined two eating habit profiles, namely, prudent-type consumers (PTc, N = 25) and Western-type consumers (WTc, N = 25), i.e., low and high consumers of western diet (WD) foods, respectively. The first two PCA dimensions, PCA1 and PCA2, were associated with different psychological components of eating and brain responses in regions involved in reward and motivation (striatum), hedonic evaluation (orbitofrontal cortex, OFC), decision conflict (anterior cingulate cortex, ACC), and cognitive control of eating (prefrontal cortex). PCA1 was inversely correlated with the FC between the right nucleus accumbens and the left lateral OFC, while PCA2 was inversely correlated with the FC between the right insula and the ACC. Our results suggest that, among a healthy population, distinct eating profiles can be detected, with specific correlates in the psychological components of eating behavior, which are also related to a modulation in the reward and motivation system during food choices. We could detect different patterns in brain functioning at rest, with reduced connectivity between the reward system and the frontal brain region in Western-type food consumers, which might be considered as an initial change toward ongoing modified cortico-striatal control.

Published
2022
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4. Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

Author

Nathalie Ganne-Carrié, Pierre Nahon, Cendrine Chaffaut, Gisèle N’Kontchou, Richard Layese, Etienne Audureau, Sylvie Chevret, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Dominique Roulot, Christophe Moreno, Alexandre Louvet, Thông Dao, Romain Moirand, Odile Goria, Eric Nguyen-Khac, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Stanislas Pol, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Jean-Marie Péron, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Jean-Pierre Bronowicki, Thomas Decaens, Ghassan Riachi, Paul Calès, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Claire Wartelle, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Brigitte Bernard-Chabert, Sophie Hillaire, and Vincent Di Martino

Subjects
alcoholic liver disease, cirrhosis, primary liver cancer, competing risk analysis, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background & Aims: In this study we aimed to analyse the impact of the aetiology of cirrhosis on the incidence, characteristics and prognosis of hepatocellular carcinoma (HCC) diagnosed during a surveillance program. Methods: Individual data from a randomized trial and 2 prospective cohorts of patients with compensated histologically proven cirrhosis recruited between 2000 and 2016 were pooled. The influence of cirrhosis aetiology on survival after HCC detection was assessed using multivariable regression models. Results: Among 3,533 patients (1,926 virus [VIR], 1,167 alcohol [ALC], 440 combined [MIX]), 431 were diagnosed with HCC after a median follow-up of 57.1 months. The 5-year HCC incidence was lowest in ALC (VIR 12.6%, ALC 9.1%, MIX 14.3%, p = 0.04). At the time of diagnosis, tumour burden and Child-Pugh score were comparable across aetiology groups, but early BCLC stages (0/A) were significantly less frequent in ALC (VIR 80%, ALC 37%, MIX 72%) as a result of worse ECOG performance status. However, similar access to first-line curative HCC treatment was reported across aetiology groups (p = 0.68). Median survival after HCC diagnosis was significantly reduced in ALC (VIR 39, ALC 21, MIX 34 months, p = 0.02). However, when adjusting for tumour size, ECOG and Child-Pugh score, the aetiology of the underlying cirrhosis no longer had a significant impact. Conclusion: Compared to patients with virus-related cirrhosis, patients with alcohol-related compensated cirrhosis enrolled in a surveillance program have: i) the lowest 5-year HCC incidence; ii) worse overall prognosis, mostly driven by a poor general condition, despite similar access to first-line curative treatment. Lay summary: It has been suggested that early detection of hepatocellular carcinoma (HCC) may be futile in patients with alcohol-related cirrhosis. By comparing outcomes in more than 3,000 patients with compensated cirrhosis included in surveillance programs, this study suggests that HCC surveillance enables early diagnosis in most patients with alcohol-related cirrhosis despite a higher competing risk of death in these patients. We also report similar access to first-line curative HCC treatment in these patients compared to those with viral cirrhosis, despite higher rates of comorbidities and impaired liver function. Following HCC detection, the later parameters were major drivers of death irrespective of the cause of cirrhosis. Registration: CHC2000 (NCT00190385) and CIRRAL (NCT01213927) cohorts were registered at ClinicalTrials.gov and the full protocols are available at the following links (https://clinicaltrials.gov/ct2/show/NCT00190385) and https://clinicaltrials.gov/ct2/show/NCT01213927, respectively). The full CirVir protocol is available via the ANRS Web site (http://anrs.fr).

Published
2021
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5. Implementation of a New Food Picture Database in the Context of fMRI and Visual Cognitive Food-Choice Task in Healthy Volunteers

Author

Yentl Gautier, Paul Meurice, Nicolas Coquery, Aymery Constant, Elise Bannier, Yann Serrand, Jean-Christophe Ferré, Romain Moirand, and David Val-Laillet

Subjects
eating habits, decision making, brain, internal conflict, healthy subjects, Psychology, BF1-990
Abstract

This pilot study aimed at implementing a new food picture database in the context of functional magnetic resonance imaging (fMRI) cognitive food-choice task, with an internal conflict or not, in healthy normal-weight adults. The database contains 170 photographs including starters, main courses, and desserts; it presents a broad-spectrum of energy content and is provided with portion weight and nutritional information. It was tested in 16 participants who evaluated the energy density and gave a liking score for all food pictures via numerical scales. First, volunteers were segregated into two groups according to their eating habits according to a food consumption frequency questionnaire (FCFQ) to assess whether the database might elicit different appreciations according to individual eating habits. Second, participants underwent fMRI cognitive food-choice task (van der Laan et al., 2014), using our picture database, in which they had to choose between high-energy (HE) and low-energy (LE) foods, under a similar liking (SL, foods with similar hedonic appraisals) condition or a different liking (DL, foods with different hedonic appraisals) condition. Participants evaluated correctly the caloric content of dishes (from r = 0.72 to r = 0.79, P < 0.001), confirming a good perception of the caloric discrepancies between food pictures. Two subgroups based on FCFQ followed by a principal component analysis (PCA) and a hierarchical ascendant classification (HAC) were defined, that is, Prudent-type (PTc, N = 9) versus Western-type (WTc, N = 7) consumers, where the WTc group showed higher consumption of HE palatable foods than PTc (P < 0.05). The WTc group showed a higher correlation between liking and caloric evaluation of the food pictures as compared to PTc (r = 0.77 and r = 0.36, respectively, P < 0.001), confirming that food pictures elicited variable responses according to contrasted individual eating habits. The fMRI analyses showed that the DL condition elicited the activation of dorsal anterior cingulate cortex (dACC), involved in internal conflict monitoring, whereas SL condition did not, and that LE food choice involved high-level cognitive processes with higher activation of the hippocampus (HPC) and fusiform gyrus compared to HE food choice. Overall, this pilot study validated the use of the food picture database and fMRI-based procedure assessing decision-making processing during a food choice cognitive task with and without internal conflict.

Published
2019
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6. Meeting of Minds around Food Addiction: Insights from Addiction Medicine, Nutrition, Psychology, and Neurosciences

Author

Aymery Constant, Romain Moirand, Ronan Thibault, and David Val-Laillet

Subjects
obesity, craving, reward circuit, motivation, cognition, behavior, Nutrition. Foods and food supply, TX341-641
Abstract

This review, focused on food addiction (FA), considers opinions from specialists with different expertise in addiction medicine, nutrition, health psychology, and behavioral neurosciences. The concept of FA is a recurring issue in the clinical description of abnormal eating. Even though some tools have been developed to diagnose FA, such as the Yale Food Addiction Scale (YFAS) questionnaire, the FA concept is not recognized as an eating disorder (ED) so far and is even not mentioned in the Diagnostic and Statistical Manuel of Mental Disorders version 5 (DSM-5) or the International Classification of Disease (ICD-11). Its triggering mechanisms and relationships with other substance use disorders (SUD) need to be further explored. Food addiction (FA) is frequent in the overweight or obese population, but it remains unclear whether it could articulate with obesity-related comorbidities. As there is currently no validated therapy against FA in obese patients, FA is often underdiagnosed and untreated, so that FA may partly explain failure of obesity treatment, addiction transfer, and weight regain after obesity surgery. Future studies should assess whether a dedicated management of FA is associated with better outcomes, especially after obesity surgery. For prevention and treatment purposes, it is necessary to promote a comprehensive psychological approach to FA. Understanding the developmental process of FA and identifying precociously some high-risk profiles can be achieved via the exploration of the environmental, emotional, and cognitive components of eating, as well as their relationships with emotion management, some personality traits, and internalized weight stigma. Under the light of behavioral neurosciences and neuroimaging, FA reveals a specific brain phenotype that is characterized by anomalies in the reward and inhibitory control processes. These anomalies are likely to disrupt the emotional, cognitive, and attentional spheres, but further research is needed to disentangle their complex relationship and overlap with obesity and other forms of SUD. Prevention, diagnosis, and treatment must rely on a multidisciplinary coherence to adapt existing strategies to FA management and to provide social and emotional support to these patients suffering from highly stigmatized medical conditions, namely overweight and addiction. Multi-level interventions could combine motivational interviews, cognitive behavioral therapies, and self-help groups, while benefiting from modern exploratory and interventional tools to target specific neurocognitive processes.

Published
2020
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7. Full-Profile Pharmacokinetic Study of High Dose Baclofen in Subjects With Alcohol Use Disorder

Author

Nicolas Simon, Romain Moirand, Maurice Dematteis, Régis Bordet, Dominique Deplanque, and Benjamin Rolland

Subjects
baclofen, alcohol use disorder, pharmacokinetics, human, clinical trial, Psychiatry, RC435-571
Abstract

Baclofen a gamma amino-butyric acid type B (GABA-B) receptor agonist, which has raised some interest for the treatment of alcohol use disorder (AUD), occasionally at dose up to 300 mg/d. We conducted the first full-profile pharmacokinetic study on baclofen in AUD subjects, up to the oral daily dose of 300 mg. Sixty subjects treated for AUD with marketed baclofen were enrolled in a prospective phase-1 study. Participants were divided into four dose groups (1: 120 mg/d-180 mg/d; and 4: >180 mg/d), and they underwent a full-profile pharmacokinetic analysis of baclofen, using a nonlinear mixed effects modeling. The influence of different clinical and biological covariates was assessed in an upward modeling. Fifty-seven participants completed the study (522 observed concentrations collected). Racemic baclofen showed a linear pharmacokinetic profile, corresponding to a one-compartment model, with no influencing clinical or biological factor. The pharmacokinetic parameters of baclofen were (bootstrap 95% confidence intervals): absorption constant (Ka) 1.64 1/h (1.34–2), clearance (Cl/F) 11.6 L/h (10.8–12.3) and volume of distribution (Vd/F) 72.8 L (66.5–80.4) leading to a half-life of 4.4 h. The interindividual variability (IIV) was 44% (19–65), 21% (16–27), and 22% (11–36) for Ka, Cl/F, and Vd/F, respectively. The residual variability was 24% (21–26). No serious adverse event was reported.Registration: EudraCT #2013-003412-46

Published
2018
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8. Determinants of Antiviral Treatment Initiation in a Hepatitis C-infected Population Benefiting from Universal Health Care Coverage

Author

Romain Moirand, Marc Bilodeau, Suzanne Brissette, and Julie Bruneau

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

BACKGROUND AND AIMS: In view of increasing therapeutic efficacy, the delivery of hepatitis C virus (HCV) antiviral treatment is expected to increase. Yet practical experience reveals a low rate of treatment, particularly among intravenous drug users. The aim of the present study was to examine the prevalence of HCV treatment and identify factors associated with HCV treatment in a population of patients evaluated in an academic hepatology outpatient clinic between 2001 and 2002.

Published
2007
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9. Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis

Author

Pierre Nahon, Jessica Bamba-Funck, Richard Layese, Eric Trépo, Jessica Zucman-Rossi, Carole Cagnot, Nathalie Ganne-Carrié, Cendrine Chaffaut, Erwan Guyot, Marianne Ziol, Angela Sutton, Etienne Audureau, Tarik Asselah, Dominique Guyader, Stanislas Pol, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Thomas Decaensi, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, null Louis d’Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Isabelle Archambeaud, Louis d’Alteroche, Frédéric Oberti, Christophe Moreno, Alexandre Louvet, Romain Moirand, Odile Goria, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, and Sylvie Chevret

Subjects
Hepatology
Abstract

This study aimed to evaluate the ability of single nucleotide polymorphisms (SNPs) to refine hepatocellular carcinoma (HCC) risk stratification.Six SNPs in PNPLA3, TM6SF2, HSD17B13, APOE, and MBOAT7 affecting lipid turnover and one variant involved in the Wnt-β-catenin pathway (WNT3A-WNT9A rs708113) were assessed in patients with alcohol-related and/or HCV-cured cirrhosis included in HCC surveillance programs (prospective CirVir and CIRRAL cohorts). Their prognostic value for HCC occurrence was assessed using Fine-Gray models combined into a 7-SNP genetic risk score (GRS). Prediction ability of two clinical scores (a routine nongenetic model determined by multivariate analysis and the external aMAP score) without then with the addition of the GRS was evaluated by C-indices. The standardized net benefit was derived from decision curves.Among 1145 patients, 86 (7.5%) developed HCC after 43.7 months. PNPLA3 and WNT3A-WNT9A variants were independently associated with HCC occurrence. The GRS stratified the population into 3 groups with progressively increased 5-yr HCC incidence [Group 1 (n=627, 5.4%), Group 2 (n=276, 10.7%), and Group 3 (n=242, 15.3%); P0.001]. The multivariate model identified age, male sex, diabetes, platelet count, GGT levels, albuminemia and the GRS as independent risk factors. The clinical model performance for 5-yr HCC prediction was similar to that of the aMAP score (C-Index 0.769). The addition of the GRS to both scores modestly improved their performance (C-Index 0.786 and 0.783, respectively). This finding was confirmed by decision curve analyses showing only fair clinical net benefit.Patients with cirrhosis can be stratified into HCC risk classes by variants affecting lipid turnover and Wnt-β-catenin pathway. The incorporation of this genetic information modestly improves the performance of clinical scores.The identification of patients at higher probability of developing liver cancer is pivotal to improve the performance of surveillance. Risk assessment can be achieved by combining several clinical and biological parameters used in routine practice. The addition of patients' genetic characteristics can modestly improve this prediction and will ultimately pave the way for precision medicine in patients eligible for HCC surveillance, allowing physicians to trigger personalized screening strategies.

Published
2023

10. Non‐invasive diagnosis of alcohol‐related steatohepatitis in patients ongoing alcohol withdrawal based on cytokeratin 18 and transient elastography

Author

Arnaud Chalin, Bruno Turlin, Ahmad Ousmen, Sophie Michalak, Johannes Mueller, Sebastian Mueller, Ludivine Legros, Edouard Bardou‐Jacquet, Jean François Viel, Michel Samson, Romain Moirand, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Universität Heidelberg [Heidelberg] = Heidelberg University, and Programme Hospitalier de Recherche Clinique, French Ministry of Health, 2012

Subjects
Hepatology, [SDV]Life Sciences [q-bio], Gastroenterology, Pharmacology (medical)
Abstract

International audience; BACKGROUND AND AIMS: The diagnosis of alcoholic steatohepatitis (ASH) is based on liver biopsy, which is costly and invasive with non-negligible morbidity. The aim of this study was to evaluate the accuracy of circulating cytokeratin 18 M65 fragment (K18-M65) alone or in association with other markers for the non-invasive diagnosis of ASH in patients ongoing alcohol withdrawal. METHODS: This study examined the serum level of K18-M65 in a test cohort of 196 patients. All patients underwent liver biopsy, transient elastography (TE) and serum collection. The diagnostic accuracy of K18-M65 alone or combined with clinico-biological data was assessed and the best defined cut-offs were validated in an independent validation cohort of 58 patients. RESULTS: K18-M65 had an area under the curve (AUC) of 0.82 (test cohort) and 0.90 (validation cohort). Using two cut-off decision points, K18-M65 was able to classify 46.9% (test cohort) and 34.5% (validation cohort) of patients with 95% sensitivity or specificity. Combining K18-M65, alpha-2-macroglobulin, TE, body mass index, and age, we created a score allowing accurate diagnosis of ASH with an AUC of 0.93 (test cohort) and 0.94 (validation cohort). This new score was able to rule out or rule in the diagnosis of steatohepatitis for probability ≤0.135 or ≥0.667 respectively in more than two-thirds of patients. CONCLUSIONS: We propose a new validated non-invasive score for the diagnosis of ASH in patients ongoing alcohol withdrawal. This score can help to identify patients that may benefit from potential therapeutics or motivate them to reduce alcohol consumption.

Published
2023

11. Low alcohol consumption influences outcomes in individuals with alcohol-related compensated cirrhosis in a French multicenter cohort

Author

Alexandre Louvet, Valérie Bourcier, Isabelle Archambeaud, Louis d’Alteroche, Cendrine Chaffaut, Frédéric Oberti, Christophe Moreno, Dominique Roulot, Thông Dao, Romain Moirand, Jean-Charles Duclos-Vallée, Odile Goria, Eric Nguyen-Khac, Stanislas Pol, Nicolas Carbonell, Jérôme Gournay, Laure Elkrief, Isabelle Fouchard-Hubert, Sylvie Chevret, Nathalie Ganne-Carrié, null Louis d’Alteroche, Jean-Marie Péron, Victor de Lédinghen, Violaine Ozenne, Jean Henrion, Albert Tran, Gabriel Perlemuter, Xavier Amiot, Jean-Pierre Zarski, CHU Lille, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Erasme [Bruxelles], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Pontchaillou [Rennes], Hôpital Paul Brousse, Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Amiens-Picardie, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIRRAL group, École pratique des hautes études (EPHE), CHU Trousseau [Tours], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), and Hopital Saint-Louis [AP-HP] (AP-HP)

Subjects
liver decompensation, [PHYS]Physics [physics], Alcohol-related liver disease, Cirrhosis, Hepatology, Recurrence, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background and aims: The harmful impact of heavy alcohol recurrence has been confirmed in patients with alcohol-related cirrhosis although this is based on old studies. The drivers of long-term outcome still need to be clearly investigated.Method: All patients with biopsy-proven compensated alcohol-related cirrhosis included in the CIRRAL cohort (22 centers) were prospectively studied. Prognostic variables of survival and liver event-free survival were assessed using multivariable Cox models with stepwise selection. The prognostic impact of alcohol recurrence during follow-up (computed in glasses-years in the same way as pack-years for tobacco) was assessed using a time-dependent covariable.Results: From 2010 to 2016, 650 patients were included. The median age at baseline was 58.4 years old, 67.4% were men and the median BMI was 27.8 kg/m2, 63.8% had a history of liver decompensation, and 70.2% had discontinued alcohol. At 5 years, 30.9% of abstinent patients developed recurrence and this risk was higher in patients with a history of drug abuse and in those with shorter alcohol discontinuation times. Median survival was 97 months. Age, alcohol consumption at baseline, platelet count and Child-Pugh score >5 were associated with overall and liver event-free survival on multivariate analysis. Alcohol consumption during follow-up of more than 25 glasses-year was independently associated with lower survival and with a trend toward significant liver event-free survival, but the risk increased from 1 glass-year, though not significantly. Simon & Makuch plots confirm the benefit of no alcohol consumption (

Published
2022

12. Effect of Prophylactic Antibiotics on Mortality in Severe Alcohol-Related Hepatitis

Author

Alexandre Louvet, Julien Labreuche, Thong Dao, Thierry Thévenot, Frédéric Oberti, Christophe Bureau, Thierry Paupard, Eric Nguyen-Khac, Anne Minello, Brigitte Bernard-Chabert, Rodolphe Anty, Faustine Wartel, Nicolas Carbonell, Georges-Philippe Pageaux, Marie-Noelle Hilleret, Romain Moirand, Pierre Nahon, Camille Potey, Alain Duhamel, and Philippe Mathurin

Subjects
General Medicine
Abstract

ImportanceThe benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear.ObjectiveTo determine the efficacy of amoxicillin-clavulanate, compared with placebo, on mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone.Design, Setting, and ParticipantsMulticenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019.InterventionPatients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147).Main Outcome and MeasuresThe primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days.ResultsAmong 292 randomized patients (mean age, 52.8 [SD, 9.2] years; 80 [27.4%] women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group [P = .33]; between-group difference, −4.7% [95% CI, −14.0% to 4.7%]; hazard ratio, 0.77 [95% CI, 0.45-1.31]). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, −11.8% [95% CI, −23.0% to −0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group).Conclusion and RelevanceIn patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis.Trial RegistrationClinicalTrials.gov Identifier: NCT02281929

Published
2023

13. French Validation of the Alcohol Urge Questionnaire: Psychometric Properties and Relationship with Alcohol Dependence and Drinking Behavior

Author

Aymery Constant, Florian Naudet, Marc Vérin, Marlene Sanz, Romain Moirand, Manon Auffret, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département des sciences humaines et sociales (SHS), CHU Pontchaillou [Rennes], Comportement et noyaux gris centraux = Behavior and Basal Ganglia [Rennes], Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Institut des Neurosciences Cliniques de Rennes = Institute of Clinical Neurosciences of Rennes (INCR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR), Institut des Neurosciences Cliniques de Rennes (INCR), EHESP, SCD, and Université de Rennes (UR)-Université européenne de Bretagne - European University of Brittany (UEB)-CHU Pontchaillou [Rennes]-Institut des Neurosciences Cliniques de Rennes (INCR)

Subjects
Male, French, Psychometrics, Health Status, medicine.medical_treatment, Craving, Severity of Illness Index, [SHS]Humanities and Social Sciences, 0302 clinical medicine, Recurrence, Surveys and Questionnaires, media_common, validation, Alcohol detoxification, General Medicine, Middle Aged, Alcoholism, Female, [SHS] Humanities and Social Sciences, France, medicine.symptom, Alcohol, Addictive behavior, Alcohol Dependence, Clinical psychology, Adult, Alcohol Drinking, Visual analogue scale, media_common.quotation_subject, Drinking Behavior, Alcohol Urge Questionnaire, Unit of alcohol, 03 medical and health sciences, medicine, Humans, Translations, Questionnaire, business.industry, Addiction, Alcohol dependence, Reproducibility of Results, medicine.disease, 030227 psychiatry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Stress, Psychological, 030217 neurology & neurosurgery
Abstract

Aim To validate a French translation of the Alcohol Urge Questionnaire (AUQ) that measures craving in patients with alcohol dependence. Method All patients aged > 18 years who were hospitalized for alcohol detoxification from February to May 2019 in the alcohol unit of the Rennes university hospital were eligible. A back-translated version of the AUQ was completed at admission. Patients were interviewed at the end of the 7-day detoxification program by a trained addiction psychiatrist (MS), using tablet computed-based questionnaires assessing state craving (visual analog scale), alcohol dependence severity, drinking behavior, psychological distress and physical/mental health. The same investigator assessed relapse 1 month after discharge. Results A total of 80 inpatients were recruited and completed questionnaires. The single factor structure of the French version of the AUQ was similar to the original questionnaire, and was supported by strong internal reliability and item-scale validity. The AUQ score correlated highly acute craving measure, but moderately scales assessing the severity of alcohol dependence, drinking behavior and mental health. Relapse 1 month after discharge was significantly related to AUQ score assessed either at baseline, or with better estimate at the end of the 7-day detoxification period. Conclusion The French version of the AUQ provides a reliable measure of phasic craving, which is best described as a context-dependent single-factor variable, related to but distinct from tonic craving, dependence severity and drinking behavior. The ease of administration makes the AUQ a useful tool for French-speaking patients with alcohol dependence.

Published
2020

14. Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

Author

Alexandre Louvet, Julien Labreuche, Christophe Moreno, Claire Vanlemmens, Romain Moirand, Cyrille Féray, Jérôme Dumortier, Georges-Philippe Pageaux, Christophe Bureau, Faïza Chermak, Christophe Duvoux, Dominique Thabut, Vincent Leroy, Nicolas Carbonell, Benjamin Rolland, Ephrem Salamé, Rodolphe Anty, Jérôme Gournay, Jean Delwaide, Christine Silvain, Valerio Lucidi, Guillaume Lassailly, Sébastien Dharancy, Eric Nguyen-Khac, Didier Samuel, Alain Duhamel, Philippe Mathurin, Christophe Berthot, Sylvie Claudet, Alexandre Doussot, Caroline Gérardin, Emilie Muel, Jean-Baptiste Hiriart, Delphine Degré, Thierry Gustot, Agnès Bonadona, Laure Bordy, Marie-Noelle Hilleret, Olivier Detry, Pierre Honoré, Nicolas Meurisse, Emmanuel Boleslawski, Dominique Deplanque, Mehdi El Amrani, Gilles Lebuffe, Guillaume Millet, Daphnée Soret, Stéphanie Truant, Domitille Erard-Poinsot, Sylvie Radenne, Stéphanie Faure, Eve Gelsi, Régine Truchi, Marika Rudler, Laëtitia Rouleau, Audrey Brenner, Hélène Larrue, Jean-Marie Péron, Marie-Angèle Robic, Teresa Antonini, Jean-Charles Duclos-Vallée, CHU Lille, Université libre de Bruxelles (ULB), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Physiopathologie et traitement des maladies du foie, Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Grenoble, Centre Hospitalier le Vinatier [Bron], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Liège (CHU-Liège), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Amiens-Picardie, Groupe de Recherche sur l'alcool et les pharmacodépendances - UMR INSERM_S 1247 (GRAP), Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Claude Huriez [Lille], Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital JeanMinjoz, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), CHU Toulouse [Toulouse], CHU Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Hépato-gastro-entérologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Référence des Maladies Rares - Maladies Inflammatoires des Voies Biliaires et Service d’Hépatologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service Universitaire d’Addictologie de Lyon [CH Le Vinatier, Bron] (Pôle MOPHA - SUAL), CHU Trousseau [Tours], Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
surgical procedures, operative, Hepatology, Hepatitis, Alcoholic, Liver Cirrhosis, Alcoholic, [SDV]Life Sciences [q-bio], Gastroenterology, Humans, Prospective Studies, Neoplasm Recurrence, Local, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Liver Transplantation
Abstract

International audience; BACKGROUND: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. METHODS: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. FINDINGS: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI -∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8-27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI -0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17-0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33-2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16-0·47] and 0·21 [0·13-0·32]). INTERPRETATION: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. FUNDING: The present study has been granted by the French Ministry of Health-Programme Hospitalier de Recherche Clinique 2010.

Published
2022

15. Obesity, Diabetes, Coffee, Tea, and Cannabis Use Alter Risk for Alcohol-Related Cirrhosis in 2 Large Cohorts of High-Risk Drinkers

Author

Florian Eyer, Suthat Liangpunsakul, Pascal Perney, Dermot Gleeson, John Whitfield, Timothy R. Morgan, Guruprasad P. Aithal, Pierre Nahon, Devanshi Seth, Felix Stickel, Steven Masson, Sylvie Naveau, Romain Moirand, Helmut K. Seitz, Lawrence Lumeng, Michael Soyka, Beat Muellhaupt, Philippe Mathurin, Paul S. Haber, Heather J. Cordell, Sebastian Mueller, Andrew Thompson, Bertrand Nalpas, Tatiana Foroud, Christopher P. Day, Munir Pirmohamed, Ann K. Daly, Jean-Marc Jacquet, QIMR Berghofer Medical Research Institute, Newcastle University [Newcastle], Indiana University System, Heidelberg University, University of Nottingham, UK (UON), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Royal Hallamshire Hospital, University of Liverpool, University hospital of Zurich [Zurich], University-Hospital Munich-Großhadern [München], Indiana University School of Medicine, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Antoine Béclère [Clamart], The University of Sydney, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), California State University [Long Beach] (CSULB ), University of California (UC), Jonchère, Laurent, Technical University of Munich (TUM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of California, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Male, medicine.medical_specialty, Cirrhosis, Alcohol Drinking, [SDV]Life Sciences [q-bio], Wine, Coffee, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Liver Cirrhosis, Alcoholic, Risk Factors, Weight loss, Germany, Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, Humans, Obesity, Medical History Taking, 2. Zero hunger, Tea, Hepatology, business.industry, Alcoholic Beverages, Smoking, Australia, Gastroenterology, Case-control study, Odds ratio, Middle Aged, medicine.disease, United Kingdom, United States, 3. Good health, [SDV] Life Sciences [q-bio], Logistic Models, Case-Control Studies, 030220 oncology & carcinogenesis, Female, Marijuana Use, 030211 gastroenterology & hepatology, France, medicine.symptom, business, Body mass index, Switzerland
Abstract

International audience; Introduction - Sustained high alcohol intake is necessary but not sufficient to produce alcohol-related cirrhosis. Identification of risk factors, apart from lifetime alcohol exposure, would assist in discovery of mechanisms and prediction of risk. Methods - We conducted a multicenter case-control study (GenomALC) comparing 1,293 cases (with alcohol-related cirrhosis, 75.6% male) and 754 controls (with equivalent alcohol exposure but no evidence of liver disease, 73.6% male). Information confirming or excluding cirrhosis, and on alcohol intake and other potential risk factors, was obtained from clinical records and by interview. Case-control differences in risk factors discovered in the GenomALC participants were validated using similar data from 407 cases and 6,573 controls from UK Biobank. Results - The GenomALC case and control groups reported similar lifetime alcohol intake (1,374 vs 1,412 kg). Cases had a higher prevalence of diabetes (20.5% (262/1,288) vs 6.5% (48/734), P = 2.27 × 10) and higher premorbid body mass index (26.37 ± 0.16 kg/m) than controls (24.44 ± 0.18 kg/m, P = 5.77 × 10). Controls were significantly more likely to have been wine drinkers, coffee drinkers, smokers, and cannabis users than cases. Cases reported a higher proportion of parents who died of liver disease than controls (odds ratio 2.25 95% confidence interval 1.55-3.26). Data from UK Biobank confirmed these findings for diabetes, body mass index, proportion of alcohol as wine, and coffee consumption. Discussion - If these relationships are causal, measures such as weight loss, intensive treatment of diabetes or prediabetic states, and coffee consumption should reduce the risk of alcohol-related cirrhosis.

Published
2020

16. Depressive symptoms are related to boredom proneness in patients receiving hospital care, regardless of alcohol status, lifestyle, or social support

Author

Aymery Constant, Ronan Thibault, Romain Moirand, David Val-Laillet, Anthony Joubert, Katia Foret, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École des Hautes Études en Santé Publique [EHESP] (EHESP), Université de Rennes 2 (UR2), Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
[SDV]Life Sciences [q-bio], media_common.quotation_subject, Hepato-gastroenterology, Alcohol, Social support, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Humans, Personality, Medicine, In patient, Life Style, Applied Psychology, Depressive symptoms, Depression (differential diagnoses), media_common, Boredom proneness, Depression, business.industry, Boredom, Hospitals, Hospital care, 030227 psychiatry, 3. Good health, chemistry, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

International audience; We examined the relationship between boredom proneness and psychological distress in patients receiving hospital care due either to excessive alcohol consumption or to gastrointestinal diseases. Sociodemographic data were collected together with boredom proneness subscales (internal/external lack of stimulation), psychological distress, physical activity, and social support. Boredom proneness due to a lack of external stimulation seemed to constitute a prominent personality trait in patients with alcohol consumption. But depressive symptoms were related only to boredom proneness due to a lack of internal stimulation in all patients, regardless of alcohol status, lifestyle, or social support. Potential implications for practice and future research are discussed.

Published
2019

17. Predictors of Short-Term Alcohol Drinking in Patients with Alcohol Use Disorders during the Third Wave of the COVID-19 Pandemic: Prospective Study in Three Addiction Outpatient Centers in France

Author

Aymery Constant, Marlène Sanz, Romain Moirand, École des Hautes Études en Santé Publique [EHESP] (EHESP), Département des sciences humaines et sociales (SHS), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CH de Saint-Malo [Broussais], CHU Pontchaillou [Rennes], and This research received no external funding.

Subjects
Adolescent, Alcohol Drinking, SARS-CoV-2, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, COVID-19, Alcoholism, Alcohol use disorders, mental disorders, Outpatients, Humans, craving, alcohol use disorders, alcohol drinking, prospective study, France, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Prospective Studies, Prospective study, Pandemics, Craving
Abstract

International audience; The present study investigates the extent to which the COVID-19 crisis disturbed different life domains of patients with alcohol use disorder (AUD) and assessed the associations between these disturbances and the risk of short-term alcohol drinking. All patients aged >18 years receiving outpatient care at three addiction treatment facilities from 15 April to 30 May 2021 were eligible for inclusion in the study. A trained resident assessed the extent to which the COVID-19 crisis affected their professional activity, social life, access to healthcare, and drinking problems, together with craving, drinking behavior, psychological distress, physical/mental health, and sociodemographic and clinical data. The same investigator assessed alcohol drinking 1 month after their visit. Nearly half of the patients felt that the COVID-19 crisis had a serious impact on their drinking problems, despite minor disruptions in access to healthcare. These disturbances significantly influenced short-term alcohol drinking in univariate analysis, together with psychological distress, craving, and drinking problems. Only craving predicted alcohol drinking in multivariate analyses, suggesting that psychological and drinking problems, as well as COVID-19 disturbances, increased the risk of alcohol drinking by increasing craving. Craving should be systematically investigated in patients with AUD to establish adapted social support systems during pandemics.

Published
2021

18. A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers

Author

Munir Pirmohamed, Guruprasad P. Aithal, Felix Stickel, Mark Thursz, David Goldman, Paul S. Haber, John Whitfield, Romain Moirand, Bertrand Nalpas, Devanshi Seth, Christophe Moreno, Andrew Thompson, Eric Trepo, Stephen R. Atkinson, Rebecca Darlay, Beat Müllhaupt, Timothy R. Morgan, Dermot Gleeson, Sylvie Naveau, Ann K. Daly, Helmut K. Seitz, Michael Soyka, Christopher P. Day, Tatiana Foroud, Jean-Marc Jacquet, Laura E. Nagy, Naga Chalasani, Pascal Perney, Philippe Mathurin, Marsha Y. Morgan, Pierre Nahon, Sebastian Mueller, Tiebing Liang, Florian Eyer, Suthat Liangpunsakul, Heather J. Cordell, Steven Masson, Tae-Hwi Schwantes-An, Ramon Bataller, Greg Botwin, Andrew McQuillin, QIMR Berghofer Medical Research Institute, Indiana University School of Medicine, Indiana University System, Newcastle University [Newcastle], University of Nottingham, UK (UON), Imperial College London, University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), California State University [Long Beach] (CSULB ), Indiana University - Purdue University Indianapolis (IUPUI), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health [Bethesda] (NIH), The University of Sydney, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Claude Huriez [Lille], CHU Lille, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University College of London [London] (UCL), Université libre de Bruxelles (ULB), University of Heidelberg, Medical Faculty, University hospital of Zurich [Zurich], Lerner Research Institute, Cleveland Clinic, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Liverpool, University-Hospital Munich-Großhadern [München], University of California, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lerner Research Institute [Cleveland, OH, USA], University of California (UC), Technical University of Munich (TUM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Liver Cirrhosis, Male, Cirrhosis, Hepatocellular carcinoma, [SDV]Life Sciences [q-bio], Alcohol, Disease, risk stratification, Gastroenterology, Oral and gastrointestinal, Cohort Studies, Liver disease, Alcohol Use and Health, Substance Misuse, chemistry.chemical_compound, 0302 clinical medicine, Liver Cirrhosis, Alcoholic, single nucleotide polymorphism, Cancer, 2. Zero hunger, 0303 health sciences, Framingham Risk Score, genome wide association, Liver Disease, Single Nucleotide, Middle Aged, Alcoholic, 3. Good health, Alcoholism, Public Health and Health Services, 030211 gastroenterology & hepatology, Female, Risk assessment, Liver Cancer, Adult, medicine.medical_specialty, Alcohol Drinking, Chronic Liver Disease and Cirrhosis, Clinical Sciences, coffee, Polymorphism, Single Nucleotide, Risk Assessment, Article, 03 medical and health sciences, GenomALC Consortium, Rare Diseases, Clinical Research, Diabetes mellitus, Internal medicine, Genetics, Diabetes Mellitus, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, Polymorphism, Metabolic and endocrine, 030304 developmental biology, Gastroenterology & Hepatology, Hepatology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Odds ratio, medicine.disease, chronic alcohol use, Good Health and Well Being, chemistry, Case-Control Studies, genome-wide association, Digestive Diseases, business, Body mass index, Genome-Wide Association Study
Abstract

International audience; BACKGROUND and AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk. METHODS: Three cohorts (GenomALC-1: n=1690, GenomALC-2: n=3037, UK Biobank: relevant n=6898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to eight genetic loci identified previously as associated with alcohol-related cirrhosis and three clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC). RESULTS: A combination of three single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated for cirrhosis risk. The odds ratio (OR) and 95% confidence intervals (CI) for the extreme score quintiles (Q1-Q5) of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18;8.60) (GenomALC-1); 2.81 (2.03;3.89) (GenomALC-2); and 3.10 (2.32;4.14) (UK Biobank). Patients with diabetes and high-risk score, compared to those without diabetes and a low-risk score, had ORs increased to 14.7 (7.69;28.1) (GenomALC-1) and 17.1 (11.3;25.7) (UK Biobank). Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76±0.06 versus 0.61±0.02, p=0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption. CONCLUSIONS: A risk score based on three genetic risk variants and diabetes status can provide meaningful risk stratification for cirrhosis in excess drinkers, allowing earlier prevention planning including intensive intervention. LAY SUMMARY: Excessive chronic drinking leads to liver cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. Our study has developed a genetic risk score (GRS) test that can identify patients at high risk and shows that the risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and high GRS. Risk assessment using this test has potential for early and personalised management of this disease in high-risk patients.

Published
2021

19. Corrigendum to: ‘A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers’ [J Hepatol 2022 (76) 275–282]

Author

John B. Whitfield, Tae-Hwi Schwantes-An, Rebecca Darlay, Guruprasad P. Aithal, Stephen R. Atkinson, Ramon Bataller, Greg Botwin, Naga P. Chalasani, Heather J. Cordell, Ann K. Daly, Christopher P. Day, Florian Eyer, Tatiana Foroud, Dermot Gleeson, David Goldman, Paul S. Haber, Jean-Marc Jacquet, Tiebing Liang, Suthat Liangpunsakul, Steven Masson, Philippe Mathurin, Romain Moirand, Andrew McQuillin, Christophe Moreno, Marsha Y. Morgan, Sebastian Mueller, Beat Müllhaupt, Laura E. Nagy, Pierre Nahon, Bertrand Nalpas, Sylvie Naveau, Pascal Perney, Munir Pirmohamed, Helmut K. Seitz, Michael Soyka, Felix Stickel, Andrew Thompson, Mark R. Thursz, Eric Trépo, Timothy R. Morgan, and Devanshi Seth

Subjects
Hepatology
Published
2022

20. Food addiction among morbidly obese patients: prevalence and links with obesity complications

Author

Aymery Constant, M. Som, Teycir Zayani, Romain Moirand, Ronan Thibault, David Val-Laillet, Estelle Le Pabic, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Rennes], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, medicine.medical_specialty, Food addiction, Medicine (miscellaneous), 030209 endocrinology & metabolism, Context (language use), Morbidly obese, Yale Food Addiction Scale, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Eating addiction, mental disorders, Prevalence, medicine, Humans, 030212 general & internal medicine, Psychiatry, Psychiatric Status Rating Scales, 2. Zero hunger, diabetes, business.industry, digestive, oral, and skin physiology, Obesity Surgery, Reproducibility of Results, Feeding Behavior, General Medicine, medicine.disease, Obesity, Obesity, Morbid, 3. Good health, obesity surgery, Psychiatry and Mental health, Clinical Psychology, Female, Food Addiction, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; In the context of obesity, little is known about the prevalence of food addiction nor about the phenotype of obese patients with food addiction. : To assess: (i) the prevalence of food addiction among obese patients eligible for obesity surgery; (ii) the relationship between clinical features and the complications of obesity. : Consecutive patients consulting for the first time were included. The Yale Food Addiction Scale (YFAS) 2.0 questionnaire was used to diagnose food addiction and its severity. Demographics, clinical features, and obesity complications were systematically collected. Statistics: Student's test was used for numerical variables and Chi-square test or Fisher's exact test for categorical variables. : A total of 292 patients were included: 79% female, age (mean ± SD) 42.6 ± 13.0 yrs., body mass index (BMI) 43.2 ± 6.8 kg/m. One hundred and eight patients (37%) had food addiction: 58% severe, 33% moderate, 9% mild. Food addiction prevalence was 39% (n = 61/156) among patients eligible for obesity surgery. Food addiction was more frequent among the unemployed, compared to professionally active patients (41.0% . 33.5%, p = 0.046). Clinical and metabolic phenotypes and obesity complications were similar between patients with and without food addiction. : Food addiction was present in 37% of obese patients, but was not associated with clinical features or obesity complications. Therefore, it should be systemically assessed for appropriate management.

Published
2021

21. Genome-wide association study and meta-analysis on alcohol-related liver cirrhosis identifies novel genetic risk factors

Author

Sebastian Mueller, Tiebing Liang, Pierre Nahon, Florian Eyer, Suthat Liangpunsakul, Devanshi Seth, Michael Soyka, Romain Moirand, David Goldman, Sylvie Naveau, Timothy R. Morgan, Beat Muellhaupt, Pascal Perney, Jean-Marc Jacquet, Helmut K. Seitz, Heather J. Cordell, Munir Pirmohamed, Guruprasad P. Aithal, Felix Stickel, Christopher P. Day, Philippe Mathurin, Dermot Gleeson, Paul S. Haber, Greg Botwin, John Whitfield, Steven Masson, Tae-Hwi Schwantes-An, Ann K. Daly, Bertrand Nalpas, Andrew Thompson, Rebecca Darlay, Tatiana Foroud, Lawrence Lumeng, Indiana University System, Newcastle University [Newcastle], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Heidelberg, Medical Faculty, University of Nottingham, UK (UON), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Royal Hallamshire Hospital, University of Liverpool, University hospital of Zurich [Zurich], Klinikum der Universität [München], Service Addictologie [CHU Nîmes] (Pôle ICAGNE), Hôpital Universitaire de Réadaptation, de Rééducation et d'Addictologie du CHU de Nîmes [Grau-du-Roi] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Antoine Béclère [Clamart], Veterans Affairs Long Beach Healthcare System (VA Long Beach Healthcare System), NSW Government, The University of Sydney, QIMR Berghofer Medical Research Institute, U01‐AA018389, National Institute on Alcohol Abuse and Alcoholism, APP1155320, National Health and Medical Research Council, Swiss Foundation for Alcohol Research, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Jonchère, Laurent, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Male, FAF2, [SDV]Life Sciences [q-bio], Genome-wide association study, Locus (genetics), Biology, lipid droplet pathway, HSD17B13, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Liver Cirrhosis, Alcoholic, Risk Factors, Databases, Genetic, medicine, Humans, Genetic Predisposition to Disease, Allele, PNPLA3, 030304 developmental biology, 2. Zero hunger, Genetics, 0303 health sciences, Hepatology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Odds ratio, Middle Aged, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV] Life Sciences [q-bio], Meta-analysis, 030211 gastroenterology & hepatology, Female, Body mass index, TM6SF2, Genome-Wide Association Study, α1-antitrypsin
Abstract

International audience; Background and aims - Only a minority of heavy drinkers progress to alcohol-associated cirrhosis (ALC). The aim of this study was to identify common genetic variants that underlie risk for ALC. Approach and results - We analyzed data from 1,128 subjects of European ancestry with ALC and 614 heavy-drinking subjects without known liver disease from Australia, the United States, the United Kingdom, and three countries in Europe. A genome-wide association study (GWAS) was performed, adjusting for principal components and clinical covariates (alcohol use, age, sex, body mass index, and diabetes). We validated our GWAS findings using UK Biobank. We then performed a meta-analysis combining data from our study, the UK Biobank, and a previously published GWAS. Our GWAS found genome-wide significant risk association of rs738409 in patatin-like phospholipase domain containing 3 (PNPLA3) (odds ratio [OR] = 2.19 [G allele], P = 4.93 × 10 ) and rs4607179 near HSD17B13 (OR = 0.57 [C allele], P = 1.09 × 10 ) with ALC. Conditional analysis accounting for the PNPLA3 and HSD17B13 loci identified a protective association at rs374702773 in Fas-associated factor family member 2 (FAF2) (OR = 0.61 [del(T) allele], P = 2.56 × 10 ) for ALC. This association was replicated in the UK Biobank using conditional analysis (OR = 0.79, P = 0.001). Meta-analysis (without conditioning) confirmed genome-wide significance for the identified FAF2 locus as well as PNPLA3 and HSD17B13. Two other previously known loci (SERPINA1 and SUGP1/TM6SF2) were also genome-wide significant in the meta-analysis. GeneOntology pathway analysis identified lipid droplets as the target for several identified genes. In conclusion, our GWAS identified a locus at FAF2 associated with reduced risk of ALC among heavy drinkers. Like the PNPLA3 and HSD17B13 gene products, the FAF2 product has been localized to fat droplets in hepatocytes. Conclusions - Our genetic findings implicate lipid droplets in the biological pathway(s) underlying ALC.

Published
2021

22. Le régime occidental ('Western diet'), l'obésité et la chirurgie bariatrique modulent successivement l'anxiété, les patterns alimentaires et les réponses cérébrales au sucre chez le miniporc Yucatan adulte

Author

Paul Meurice, Mathilde Maherault, Romain Moirand, Charles-Henri Malbert, Yentl Gautier, David Val-Laillet, Noémie Réthoré, Yann Serrand, Damien Bergeat, Nicolas Coquery, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], US 1395 ANI-SCAN [INRA], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and This study was funded by the Hed-O-Shift INRAE Priority Action of the AlimH Division (Nutrition, Chemical Food Safety and Consumer Behaviour)

Subjects
Sucrose, Swine, Bariatric Surgery, lcsh:Medicine, Diseases, Anxiety, Eating, 0302 clinical medicine, Weight loss, Medicine, Psychology, Attention, lcsh:Science, 2. Zero hunger, Multidisciplinary, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Brain, Cognition, 3. Good health, Survival Rate, Eating disorders, Swine, Miniature, medicine.symptom, medicine.medical_specialty, 030209 endocrinology & metabolism, Article, 03 medical and health sciences, Food Preferences, Internal medicine, Weight Loss, Animals, Obesity, Memory Disorders, Motivation, business.industry, Working memory, [SCCO.NEUR]Cognitive science/Neuroscience, lcsh:R, medicine.disease, Endocrinology, Glucose, Diet, Western, Positron-Emission Tomography, lcsh:Q, business, Weight gain, Insula, 030217 neurology & neurosurgery, Neuroscience
Abstract

Palatable sweet/fatty foods overconsumption is a major risk factor for obesity and eating disorders, also having an impact on neuro-behavioural hedonic and cognitive components comparable to what is described for substance abuse. We hypothesized that Yucatan minipigs would show hedonic, cognitive, and affective neuro-behavioral shifts when subjected to western diet (WD) exposure without weight gain, after the onset of obesity, and finally after weight loss induced by caloric restriction with (RYGB) or without (Sham) gastric bypass. Eating behavior, cognitive and affective abilities were assessed with a spatial discrimination task (holeboard test) and two-choice feed tests. Brain responses to oral sucrose were mapped using 18F-FDG positron emission tomography. WD exposure impaired working memory and led to an “addiction-type” neuronal pattern involving hippocampal and cortical brain areas. Obesity induced anxiety-like behavior, loss of motivation, and snacking-type eating behavior. Weight loss interventions normalized the motivational and affective states but not eating behavior patterns. Brain glucose metabolism increased in gustatory (insula) and executive control (aPFC) areas after weight loss, but RYGB showed higher responses in inhibition-related areas (dorsal striatum). These results showed that diet quality, weight loss, and the type of weight loss intervention differently impacted brain responses to sucrose in the Yucatan minipig model.

Published
2020

23. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis

Author

Pierre Nahon, Marie Najean, Richard Layese, Kevin Zarca, Laeticia Blampain Segar, Carole Cagnot, Nathalie Ganne-Carrié, Gisèle N’Kontchou, Stanislas Pol, Cendrine Chaffaut, Fabrice Carrat, Maxime Ronot, Etienne Audureau, Isabelle Durand-Zaleski, Tarik Asselah, Dominique Guyader, Hélène Fontaine, Georges-Philippe Pageaux, Victor De Lédinghen, Denis Ouzan, Fabien Zoulim, Dominique Roulot, Albert Tran, Jean-Pierre Bronowicki, Thomas Decaensi, Ghassan Riachi, Paul Calès, Jean-Marie Péron, Laurent Alric, Marc Bourlière, Philippe Mathurin, Sebastien Dharancy, Jean-Frédéric Blanc, Armand Abergel, Olivier Chazouillères, Ariane Mallat, Jean-Didier Grangé, Pierre Attali, Louis d’Alteroche, Claire Wartelle, Thông Dao, Dominique Thabut, Christophe Pilette, Christine Silvain, Christos Christidis, Eric Nguyen-Khac, Brigitte Bernard-Chabert, Sophie Hillaire, Vincent Di Martino, Delphine Bonnet, Virginie Payssan-Sicart, Chloe Pomes, François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig-Lavie, Marianne Maynard, Eric Billaud, David Boutoille, Morane Cavellec, Marjorie Cheraud-Carpentier, Isabelle Hubert, Jaouad Benhida, Adrien Lannes, Françoise Lunel, Frédéric Oberti, Nathalie Boyer, Nathalie Giuily, Corinne Castelnau, Giovanna Scoazec, Aziza Chibah, Sylvie Keser, Karim Bonardi, Anaïs Vallet-Pichard, Philippe Sogni, Juliette Foucher, Jean-Baptiste Hiriart, Amy Wilson, Sarah Shili, Faiza Chermak, Christelle Ansaldi, Nisserine Ben Amara, Laëtitia Chouquet, Emilie De Luca, Valérie Oules, Rodolphe Anty, Eve Gelsi, Régine Truchi, Elena Luckina, Nadia Messaoudi, Joseph Moussali, Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed, Véronique Grando-Lemaire, Valérie Bourcier, Séverine Brulé, Thomas Stalhberger, Caroline Jezequel, Audrey Brener, Anne Laligant, Aline Rabot, Isabelle Renard, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo-Noumbissie, Esma Razi, Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani-Nani, Marie-Albertine Bernard, Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Marie Pierre Ripault, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo, Marine Faure, Bruno Froissart, Marie-Noelle Hilleret, Jean-Pierre Zarski, Odile Goria, Victorien Grard, Hélène Montialoux, Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault, Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty, Teresa Antonini, Audrey Coilly, Jean-Charles Duclos Vallée, Mariagrazia Tateo, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti, Abdenour Babouri, Virginie Filipe, Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah, Paul Carrier, Maryline Debette-Gratien, Jérémie Jacques, Guillaume Lassailly, Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet, Marianne Latournerie, Marc Bardou, Thomas Mouillot, Yannick Bacq, Didier Barbereau, Charlotte Nicolas, Caroline Chevalier, Isabelle Archambeaud, Sarah Habes, Danièle Botta-Fridlund, Eric Saillard, Marie-Josée Lafrance, Patrice Cacoub, Patrizia Carrieri, Elisabeth Delarocque-Astagneau, Victor De Ledinghen, Céline Dorival, Jean Dubuisson, Chantal Housset, Dominique Larrey, Patrick Marcellin, Jean-Michel Pawlotsky, Ventzislava Petrov-Sanchez, Sophie Vaux, Linda Wittkop, Yazdan Yazdanpanah, Jessica Zucman-Rossi, Christophe Moreno, Romain Moirand, Nicolas Carbonell, Jean-Charles Duclos-Vallée, Victor de Ledinghen, Violaine Ozenne, Jean Henrion, Gabriel Perlemuter, Xavier Amiot, Sylvie Chevret, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC] (FunGeST), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Henri Mondor, Unité de recherche clinique en économie de la santé [Paris] (URC Eco), Délégation de la Recherche Clinique et de l’Innovation [Paris] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de santé publique [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), ANRS|Maladies infectieuses émergentes (ANRS|MIE), Université Sorbonne Paris Nord, Hôpital Cochin [AP-HP], Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de santé publique [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Hôpital Beaujon [AP-HP]

Subjects
AMRI, abbreviated magnetic resonance imaging, NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, Cirrhosis, Cost effectiveness, [SDV]Life Sciences [q-bio], Population, TACE, transarterial chemoembolization, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Gastroenterology, QALY, quality-adjusted life year, Internal medicine, Internal Medicine, LY, life years, Immunology and Allergy, Medicine, Early Hepatocellular Carcinoma, liver cancer risk, education, cost-effectiveness, RFA, radiofrequency ablation, education.field_of_study, AFP, alpha-fetoprotein, US, ultrasound, Hepatology, medicine.diagnostic_test, business.industry, cirrhosis, LYG, life years gained, Incidence (epidemiology), BCLC, Barcelona Clinic Liver Cancer, ICER, incremental cost-effectiveness ratio, Magnetic resonance imaging, medicine.disease, HR, hazard ratio, digestive system diseases, Hepatocellular carcinoma, SHR, subdistribution hazard ratio, surveillance, HCC, hepatocellular carcinoma, business, MRI, magnetic resonance imaging, Incremental cost-effectiveness ratio, Research Article, MRI
Abstract

Background & Aims Reinforced hepatocellular carcinoma (HCC) surveillance using magnetic resonance imaging (MRI) could increase early tumour detection but faces cost-effectiveness issues. In this study, we aimed to evaluate the cost-effectiveness of MRI for the detection of very early HCC (Barcelona Clinic Liver Cancer [BCLC] 0) in patients with an annual HCC risk >3%. Methods French patients with compensated cirrhosis included in 4 multicentre prospective cohorts were considered. A scoring system was constructed to identify patients with an annual risk >3%. Using a Markov model, the economic evaluation estimated the costs and life years (LYs) gained with MRI vs. ultrasound (US) monitoring over a 20-year period. The incremental cost-effectiveness ratio (ICER) was calculated by dividing the incremental costs by the incremental LYs. Results Among 2,513 patients with non-viral causes of cirrhosis (n = 840) and/or cured HCV (n = 1,489)/controlled HBV infection (n = 184), 206 cases of HCC were detected after a 37-month follow-up. When applied to training (n = 1,658) and validation (n = 855) sets, the construction of a scoring system identified 33.4% and 37.5% of patients with an annual HCC risk >3% (3-year C-Indexes 75 and 76, respectively). In patients with a 3% annual risk, the incremental LY gained with MRI was 0.4 for an additional cost of €6,134, resulting in an ICER of €15,447 per LY. Compared to US monitoring, MRI detected 5x more BCLC 0 HCC. The deterministic sensitivity analysis confirmed the impact of HCC incidence. At a willingness to pay of €50,000/LY, MRI screening had a 100% probability of being cost-effective. Conclusions In the era of HCV eradication/HBV control, patients with annual HCC risk >3% represent one-third of French patients with cirrhosis. MRI is cost-effective in this population and could favour early HCC detection. Lay summary The early identification of hepatocellular carcinoma in patients with cirrhosis is important to improve patient outcomes. Magnetic resonance imaging could increase early tumour detection but is more expensive and less accessible than ultrasound (the standard modality for surveillance). Herein, using a simple score, we identified a subgroup of patients with cirrhosis (accounting for >one-third), who were at increased risk of hepatocellular carcinoma and for whom the increased expense of magnetic resonance imaging would be justified by the potential improvement in outcomes., Graphical abstract, Highlights • HCC risk stratification in patients with cirrhosis aims at improving performance of cancer surveillance. • Using a simple scoring system, one-third of patients with cirrhosis with an annual HCC risk >3% can be easily identified. • Semi-annual surveillance using MRI in this population could enable the cost-effective detection of 5x more BCLC 0 HCCs.

Published
2022

24. Addiction Alimentaire : prévalence, phénotype métabolique, et succès du traitement nutritionnel chez des patients obèses consultant dans un centre spécialisé

Author

Aymery Constant, T. Zayani, M. Som, Ronan Thibault, Romain Moirand, David Val-Laillet, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
2. Zero hunger, 0303 health sciences, Promotion de la santé, Nutrition and Dietetics, 030309 nutrition & dietetics, Endocrinology, Diabetes and Metabolism, Addiction alimentaire, [SHS.PSY]Humanities and Social Sciences/Psychology, 030209 endocrinology & metabolism, 3. Good health, Troubles du comportement alimentaire, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Obésité
Abstract

Introduction et but de l’etude Chez le patient obese, les troubles du comportement alimentaire sont frequents, et parfois associes au diagnostic d’addiction alimentaire (AA). Leur meconnaissance pourrait expliquer l’echec de la prise en charge. Peu de donnees existent sur la prevalence et le phenotype metabolique des patients obeses ayant une AA. Son diagnostic repose sur le questionnaire Yale Food Addiction Scale (YFAS) 2.0. Objectifs dans une population de patients obeses presentant les criteres d’eligibilite a la chirurgie de l’obesite, determiner la prevalence de l’AA, le phenotype clinique et metabolique des patients AA, determiner les facteurs impliques dans la reponse au traitement de l’obesite dont l’AA. Materiel et methodes Tous les patients obeses consultant pour la 1re fois dans notre unite de nutrition de decembre 2016 a mars 2019 ont ete inclus. Le questionnaire YFAS 2.0 a ete rempli par chaque patient, et leurs donnees sociodemographiques, cliniques et metaboliques ont ete collectees. Le succes du traitement nutritionnel pre-operatoire a ete evalue a 6 mois et/ou 1 an par la perte de poids (a 6 mois : > 5 % du poids initial ou > 25 % de l’exces de poids, a 1 an : > 10 % du poids initial ou > 50 % de l’exces de poids). Statistique : t Student, Mann–Whitney, Wilcoxon, Chi2, Fisher exact. Analyses univariee et multivariee pour determiner les variables impliquees dans la reponse au traitement. Resultats et analyse statistique Parmi les 384 questionnaires distribues, 292 ont ete analyses (taux de non remplissage : 24 %) : 80 % de femmes, âge moyen 42,6 ± 13,0, ans, indice de masse corporelle (IMC) moyen, 43,2 ± 6,8. La prevalence de l’AA etait de 37 % (n = 108) dans l’ensemble de notre population. Parmi ceux-ci, 58 % avait une AA severe, 33 %, moderee et 9 %, legere. L’AA touchait davantage les patientes sans emploi que celles actives (41 % versus 33,5 % p = 0,046). Le profil clinique et metabolique ainsi que la prevalence des complications medicales de l’obesite, ne differaient pas entre AA et non AA. En analyse multivariee, l’âge (OR = 1,56 [1,14 ; 2,14], p = 0,0058), l’IMC (OR = 1,29 [1,01 ; 1,65], p = 0,0378) ainsi que les douleurs articulaires (OR = 3,10 [1,15 ; 8,35, p = 0,0248]), mais pas l’AA, etaient significativement associes a un moindre succes de la perte de poids a 6 mois et/ou 1 an. Conclusion Trente-sept pour cent des patients obeses consultant pour la 1re fois dans notre centre rapportaient une AA. Nous n’avons pas identifie de phenotype sociodemographique, clinique ou metabolique du patient obese avec AA. L’AA n’etait pas associee a la severite de l’obesite ou a ses comorbidites et n’etait pas predictive du succes du traitement.

Published
2020

25. Prognosis of alcoholic or viral B/C cirrhosis according to ABO blood group: results of abocirralvir, from CIRRAL and ANRS CO12 CirVir cohorts

Author

Isabelle Ollivier-Hourmand, Pierre Nahon, Cendrine Chaffaut, Thong Dao, Nga Nguyen, Marcellin Patrick, Dominique Roulot, Victor de Lédinghen, Stanislas Pol, Dominique Guyader, Isabelle Mabile-Archambeaud, Fabien Zoulim, Frédéric Oberti, Albert Tran, Jean-Pierre Bronowicki, Louis Dalteroche, Denis Ouzan, Jean Marie Peron, Jean-Pierre Zarski, Marc Bourliere, Dominique Larrey, Alexandre Louvet, Paul Cales, Armand Abergel, Philippe Mathurin, Ariane Mallat, Jean-Frédéric Blanc, Eric Nguyen Khac, Ghassan Riachi, Laurent Alric, Lawrence Serfaty, Tereza Antonini, Christophe Moreno, Pierre Attali, Dominique Thabut, Christophe Pilette, Jean Didier Grange, Christine Silvain, Nicolas Carbonell, Brigitte Bernard Chabert, Odile Goria, Claire Wartelle-Bladou, Romain Moirand, Christos Christidis, Gabriel Perlemuter, Violaine Ozenne, Jean Henrion, Sophie Hillaire, Vincent Di Martino, Xavier Amiot, Angela Sutton, Nathalie Barget, Yohann Repesse, Sylvie Chevret, and Nathalie Ganne-Carrié

Subjects
Hepatology
Published
2020

26. L’addiction alimentaire diagnostiquée par la Yale Food Addiction Scale version 2,0 est fréquente chez les patients obèses mais n’est pas associée aux complications de l’obésité

Author

Romain Moirand, Aymery Constant, M. Som, David Val-Laillet, Ronan Thibault, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département des sciences humaines et sociales (SHS), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
0303 health sciences, Promotion de la santé, Nutrition and Dietetics, 030309 nutrition & dietetics, Endocrinology, Diabetes and Metabolism, Addiction alimentaire, [SHS.PSY]Humanities and Social Sciences/Psychology, 030209 endocrinology & metabolism, 3. Good health, Troubles du comportement alimentaire, 03 medical and health sciences, 0302 clinical medicine, Internal Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Obésité
Abstract

Discipline Clinique. Introduction et but de l’etude L’obesite est une pandemie responsable de nombreuses complications. L’addiction alimentaire (AA) est un concept recent pouvant expliquer en partie l’echec de la prise en charge de l’obesite. L’objectif de notre etude etait donc de determiner la prevalence de l’AA dans une population de patients obeses eligibles a la chirurgie de l’obesite, et le phenotype clinique du patient obese ayant une AA. Materiel et methodes Le Yale Food Addiction Scale (YFAS) 2,0 est le questionnaire valide qui a ete utilise pour le diagnostic d’AA. Il etait rempli par chaque nouveau patient consultant dans l’unite de nutrition pour la prise en charge d’une obesite. Les donnees sociodemographiques et cliniques etaient collectees retrospectivement a partir de patients obeses vus en consultation de nutrition de decembre 2016 a mars 2018. Tous les patients ayant rempli le questionnaire YFAS ont ete inclus dans l’analyse. Les donnees qualitatives etaient analysees a l’aide du test du Chi2 ou Fisher exact et les donnees quantitatives par l’analyse de variance a un facteur (ANOVA). Resultats et analyse statistique Deux cent vingt-six patients obeses ont rempli le questionnaire YFAS 2,0. Parmi ces patients, 44 (19 %) ont ete exclus de l’analyse car les questionnaires etaient mal remplis. Quatre-vingt pour cent etaient des femmes. L’âge moyen etait de 43,3 ans (± 13,7). L’indice de masse corporelle (IMC) moyen etait de 42,9 kg/m2 (± 6,6). La prevalence d’AA etait de 33 % (n = 60/182). Parmi ceux-ci, 57 % avait une AA severe, 35 % une moderee et 8 % une legere. Parmi les patients eligibles a une chirurgie de l’obesite 39 % (n = 34/88) avaient une AA. L’AA touchait davantage les femmes et cela de maniere significative : 37 % des femmes et 17 % des hommes (p = 0,02). Les donnees sociodemographiques telles que l’âge, la profession, le statut marital, la parentalite, le lieu de residence et l’IMC ne differaient significativement pas entre AA et non AA. Il en etait de meme pour la prevalence des complications medicales (diabete, hypertension arterielle, infarctus du myocarde, syndrome metabolique, dyslipidemie, steatose hepatique, syndrome d’apnees obstructives du sommeil, dyspnee). Conclusion Pres de 40 % des patients obeses eligibles a la chirurgie de l’obesite et adresses dans notre centre de reference rapportaient une AA. Cependant, l’AA n’etait pas associee aux complications de l’obesite. Il reste maintenant a determiner si la presence d’une AA est ou non predictive du succes de la prise en charge medico-chirurgicale de l’obesite, et si une prise en charge addictologique personnalisee dediee permettrait le maintien de la perte de poids a long terme.

Published
2019

27. Effect of a brief motivational intervention in reducing alcohol consumption in the emergency department a randomized controlled trial

Author

Cristina Diaz Gomez, Romain Moirand, Nathalie Le Garjean, Muriel Lasbleiz, François Jerome Kerdiles, Abdelouahab Bellou, Marcus Ngantcha, Nadine Brouard, Mathieu Perennes, Caroline Le Lan, Observatoire Français des Drogues et toxicomanies, CHU Pontchaillou [Rennes], Service des urgences [Rennes] = Emergency [Rennes], Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Harvard Medical School [Boston] (HMS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service des urgences [Rennes], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Harvard Medical School [Boston] ( HMS )

Subjects
Male, medicine.medical_specialty, Adolescent, Alcohol Drinking, [SDV]Life Sciences [q-bio], Alcohol, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Randomized controlled trial, law, Intervention (counseling), Medicine, Humans, 030212 general & internal medicine, Young adult, Motivation, [ SDV ] Life Sciences [q-bio], business.industry, 030208 emergency & critical care medicine, Emergency department, Confidence interval, humanities, 3. Good health, chemistry, Relative risk, Emergency Medicine, Physical therapy, Female, business, Emergency Service, Hospital, Alcohol consumption, Alcoholic Intoxication
Abstract

International audience; Background - Introduction to alcohol consumption early in life increases the risk of alcohol dependency and hence motivational interventions are needed in young patients visiting the emergency department (ED). Aim - This study aims to investigate the efficacy of a brief motivational intervention in reducing alcohol consumption among young ED patients. Patients and methods - This was a blind randomized controlled trial with follow-up at 3 months. Patients were stratified on the basis of age and blood alcohol level of 0.5 g/l or more. A total of 263 patients aged 16-24 were randomized, with 132 patients in the brief motivational intervention group and 131 in the control group, with data collection at 3 months. From September 2011 to July 2012, a psychologist performed the brief motivational intervention 5 days after the patients' discharge. A phone call was made at 1 and 2 months. The control group received a self-assessment leaflet. The reduction in consumption was determined on the basis of the number of drinks consumed in the last week prior to the survey. Results - The mean reduction between number of drinks at baseline and number of drinks at 3 months in the control group was 0.3 and that in the intervention group was 0.9. This reduction in alcohol use in the brief motivational intervention group was not significant. The study did not show an association between brief motivational intervention and repeated drunkenness [relative risk (RR): 0.99, 95% confidence interval (CI): 0.79-1.24], alcohol consumption at least once a month (RR: 0.81, 95% CI: 0.31-2.10) and alcohol consumption at least 10 times during the month (RR: 1.1, 95% CI: 0.96-1.26). Conclusion - We did not observe a significant decrease in alcohol consumption among the youth. Further studies are needed to confirm the positive impact of a brief motivational intervention in the ED.

Published
2019

28. Emotional overeating is common and negatively associated with alcohol use in normal-weight female university students

Author

Romain Moirand, Aymery Constant, David Val-Laillet, Nicolas Coquery, Yentl Gautier, Ronan Thibault, École des Hautes Études en Santé Publique [EHESP] (EHESP), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], INRA Priority Action of the AlimH Division, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
0301 basic medicine, Adult, Adolescent, Alcohol Drinking, Universities, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Emotions, Anger, Anxiety, Hyperphagia, Body Mass Index, Feeding and Eating Disorders, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Surveys and Questionnaires, Adaptation, Psychological, medicine, Humans, 030212 general & internal medicine, Overeating, Disordered eating, Students, General Psychology, media_common, Emotion, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, 4. Education, Loneliness, Emotional eating, medicine.disease, Food questionnaires, 3. Good health, Substance abuse, Eating disorders, Female, medicine.symptom, Coping, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Clinical psychology
Abstract

introduction Eating in response to specific emotional cues was hitherto investigated in relation to weight gain, eating disorders, and psychiatric and addictive disorders. Given the difficulties in treating established obesity, preventive interventions towards normal-weight subjects could be more appropriate and cost effective. In order to design such interventions, it is important to characterize emotional overeating in normal-weight subjects, especially young women. Methods Female university students aged 18–24 years with healthy Body Mass Index (comprised between 18.5 and 24.9) were asked to complete questionnaires while attending a medical consultation. Emotional Eating frequency in the last 28 days was assessed together with data on habitual physical activity, drinking patterns, substance abuse, suspected eating disorders and cognitive/behavioural components of eating. Sociodemographic data and tobacco use were also collected. Results Half of participants reported intermittent Emotional Overeating in the last 28 days, mostly during one to five days in the last 28 days, in response to Anxiety (51.3%), Loneliness (45.1%), Sadness (44.8%), and Happiness (43.6%), and to a lesser extent in response to Tiredness (27.4%) and Anger (14.6%). In multivariate analysis, Distress-Induced Overeating (DIO) correlated positively with inability to resist emotional cues, disordered eating symptoms, and loss of control over food intake. It correlated negatively with moderate and excessive drinking. Conclusion A large proportion of normal-weight female students used intermittent overeating episodes as a time-limited response to emotional states, especially anxiety. DIO was negatively correlated with alcohol use, which suggests two distinct and somewhat exclusive ways of coping with negative emotions. It was higher in the minority of students with disordered eating symptoms and loss of control over food intake, highlighting the need for a systematic screening in all female students entering college.

Published
2018

30. Prevalence of food addiction (FA) diagnosed by the yale food addiction scale version 2.0 (YFAS 2.0): Prospective study in a referral centre for obesity surgery

Author

Romain Moirand, Ronan Thibault, Aymery Constant, M. Som, David Val-Laillet, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département des sciences humaines et sociales (SHS), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
0301 basic medicine, medicine.medical_specialty, 030109 nutrition & dietetics, Nutrition and Dietetics, Food addiction, business.industry, Obesity Surgery, [SHS.PSY]Humanities and Social Sciences/Psychology, Critical Care and Intensive Care Medicine, 3. Good health, 03 medical and health sciences, Referral centre, medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Obesity, Psychiatry, Prospective cohort study, business, Yale Food Addiction Scale
Abstract

International audience; Rationale: Obesity is pandemic. Eating disorders is one of the causative factors. Obesity surgery offers better long-term outcomes than standard medical therapy. Nevertheless, about 20 to 30% of operated obese patients regain weight. That could be explained in many instances by an insufficient management of preoperative eating disorders including FA. The prevalence of FA is not known in obese patients eligible for obesity surgery. The main aim is to identify the prevalence of FA in a cohort of obese patients eligible for obesity surgery.Methods: FA was diagnosed by the validated questionnaire YFAS 2.0. 246 questionnaires were retrospectively analyzed. Each patient consulting in our centre between June 2016 and March 2018 systematically filled out the YFAS 2.0. FA was classified as absence, low, moderate or severe, according to the recommended questionnaire interpretation.Results: Among 246 patients, mean age was 42.5 years old (+/- 13.6), 195 were women (79%). 131 patients (53%) did not have FA. 67 (27%) patients had FA (mean age, 39.3±12.0 yrs; women, n=60 (90%)). Among the 67 patients who had a FA, 6 (9%) had low FA, 22 (33%) moderate FA, and 39 (58%) severe FA. 48 (20%) were not classified because of questionnaires that were partially filled in. At ESPEN congress, more data regarding patients’ profile, including obesity-related complications, will be reported.Conclusions: FA is reported in one third of obese patients referred for obesity surgery. Our study highlighted that many patients did not fill totally the questionnaire, and the subjectivity of the results obtained from a declarative questionnaire. This reinforces the idea that objective criteria, e.g. brain functional magnetic resonance imaging, are needed to diagnose FA and best orientate obese patients’ therapy.

Published
2018

31. Reduced phenotypic expression in genetic hemochromatosis with time: Role of exposure to non-genetic modifiers

Author

Romain Moirand, Yves Deugnier, Dominique Guyader, Anne-Sophie Bollard, Jeff Morcet, Houda Hamdi-Rozé, Edouard Bardou-Jacquet, Fabrice Lainé, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], The authors would like to thank all medical doctors from the Liver Unit in Rennes for allowing them to include their patients in the present study, the nursing staff for the daily care of the patients, Michèle Perrin for keeping track of patient records and maintaining the database, Béatrice Leclerc for managing the administration and organizing family screening procedures, and Stuart Byrom (Direction de la Recherche et de l'Innovation, CHU de Rennes) for reviewing the English version of the manuscript., and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Male, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Physiology, Overweight, tobacco, 0302 clinical medicine, Medicine, Prospective Studies, Child, Aged, 80 and over, education.field_of_study, biology, medicine.diagnostic_test, alcohol, HFE Hemochromatosis, Middle Aged, Penetrance, 3. Good health, Phenotype, Child, Preschool, 030211 gastroenterology & hepatology, Female, Hemochromatosis, medicine.symptom, Adult, Adolescent, Genotype, Population, 03 medical and health sciences, BMI, Young Adult, Hepcidin, Diabetes mellitus, evolution over time, Humans, Genetic Testing, education, Hemochromatosis Protein, Genetic testing, Aged, Retrospective Studies, Hepatology, business.industry, Transferrin saturation, Infant, Newborn, Infant, DNA, medicine.disease, 030104 developmental biology, Mutation, biology.protein, business, Follow-Up Studies
Abstract

International audience; Background & aims - Genetic hemochromatosis is mainly related to the homozygous p.Cys282Tyr (C282Y) mutation in the HFE gene, which causes hepcidin deficiency. Its low penetrance suggests the involvement of cofactors that modulate its expression. We aimed to describe the evolution of disease presentation and of non-genetic factors liable to impact hepcidin production in the long term. Methods - Clinical symptoms, markers of iron load, and risk factors according to the year of diagnosis were recorded over 30 years in a cohort of adult C282Y homozygotes. A total of 2,050 patients (1,460 probands [804 males and 656 females] and 542 relatives [244 males and 346 females]) were studied. Results - Over time: (i) the proband-to-relative ratio remained roughly stable; (ii) the gender ratio tended towards equilibrium among probands; (iii) age at diagnosis did not change among males and increased among females; (iv) the frequency of diabetes and hepatic fibrosis steadily decreased while that of chronic fatigue and distal joint symptoms remained stable; (v) transferrin saturation, serum ferritin and the amount of iron removed decreased; and (vi) the prevalence of excessive alcohol consumption decreased while that of patients who were overweight increased. Tobacco smoking was associated with increased transferrin saturation. Conclusion - Genetic testing did not alter the age at diagnosis, which contrasts with the dramatic decrease in iron load in both genders. Tobacco smoking could be involved in the extent of iron loading. Besides HFE testing, which enables the diagnosis of minor forms of the disease, the reduction of alcohol consumption and the increased frequency of overweight patients may have played a role in the decreased long-term iron load, as these factors are likely to improve hepcidin production. Lay summary - Genetic hemochromatosis is an inherited disorder that leads to progressive iron overload in the body. It results in chronic fatigue and in potential liver (cirrhosis), pancreas (diabetes) and joint (arthritis) damage in adulthood. The present study showed that tobacco smoking may aggravate iron loading, but that hemochromatosis has become less and less severe over the last 30 years despite patients being older at diagnosis, likely because of the protective effects of lower alcohol consumption and of increased weight in the French population.

Published
2018

32. Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis

Author

Jean-Marie Péron, Jean-Pierre Zarski, Perarnau Jm, Albert Tran, Dominique Roulot, Isabelle Archambeaud, Xavier Amiot, Nicolas Carbonell, Odile Goria, Cendrine Chaffaut, Frédéric Oberti, Eric Nguyen-Khac, Violaine Ozenne, Alexandre Louvet, Stanislas Pol, Gabriel Perlemuter, Sylvie Chevret, Thong Dao, Christophe Moreno, Nathalie Ganne-Carrié, Jean Henrion, Valérie Bourcier, Teresa Antonini, Michel Beaugrand, Victor de Lédinghen, Romain Moirand, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13), Université Sorbonne Paris Cité (USPC), Ligue Nationale Contre le Cancer - Paris, Ligue Nationale Contre le Cancer (LNCC), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Université Paris Diderot - Paris 7 (UPD7)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Unité d'Hématologie [Bruxelles, Belgium] (CUB Hôpital Erasme), Université libre de Bruxelles (ULB)-CUB Hôpital Erasme [Bruxelles, Belgium], Unité d'Hématologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), CHU Amiens-Picardie, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Paul Brousse, Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hôpital Lariboisière-Fernand-Widal [APHP], Unité d'Hématologie [CH de Jolimont-Lobbes, Belgium], Centre Hospitalier de Jolimont-Lobbes [Haine Saint-Paul, Belgium], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), AP-HP - Hôpital Antoine Béclère [Clamart], CHU Tenon [AP-HP], CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, The promoter of the study was the Assistance Publique des Hôpitaux de Paris (APHP), and the cohort was funded by the Institut National du Cancer (INCa) and the French Association for Research in Cancer and the National Agency for Research on HIV and Hepatitis., Jonchère, Laurent, Université Fédérale Toulouse Midi-Pyrénées, Ligue Nationnale Contre le Cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université Libre de Bruxelles [Bruxelles] (ULB)-CUB Hôpital Erasme [Bruxelles, Belgium], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [APHP], CHU Cochin [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP], Hôpital Lariboisière, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Antoine Béclère, CHU Tenon [APHP], Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
Male, Alcoholic liver disease, Cirrhosis, Biopsy, Gastroenterology, Liver disease, 0302 clinical medicine, Liver Cirrhosis, Alcoholic, Risk Factors, Gastro-entérologie, Prospective Studies, HCC, Prospective cohort study, education.field_of_study, Mortality rate, Incidence (epidemiology), Incidence, Liver Neoplasms, Age Factors, Middle Aged, Progression-Free Survival, 3. Good health, Liver, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Prothrombin, alpha-Fetoproteins, medicine.medical_specialty, Carcinoma, Hepatocellular, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Milan criteria, 03 medical and health sciences, Competing risk analysis, Sex Factors, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, education, Aged, Hepatology, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Bilirubin, medicine.disease, digestive system diseases, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, Compensated cirrhosis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract

Background & Aims: More than 90% of cases of hepatocellular carcinoma (HCC) occur in patients with cirrhosis, of which alcohol is a major cause. The CIRRAL cohort aimed to assess the burden of complications in patients with alcoholic cirrhosis, particularly the occurrence of HCC. Methods: Patients with biopsy-proven compensated alcoholic cirrhosis were included then prospectively followed. The main endpoint was the incidence of HCC. Secondary outcomes were incidence of hepatic focal lesions, overall survival (OS), liver-related mortality and event-free survival (EFS). Results: From October 2010 to April 2016, 652 patients were included in 22 French and Belgian centers. During follow-up (median 29 months), HCC was diagnosed in 43 patients. With the limitation derived from the uncertainty of consecutive patients’ inclusion and from a sizable proportion of dropouts (153/652), the incidence of HCC was 2.9 per 100 patient-years, and one- and two-year cumulative incidences of 1.8% and 5.2%, respectively. Although HCC fulfilled the Milan criteria in 33 cases (77%), only 24 patients (56%) underwent curative treatment. An explorative prognostic analysis showed that age, male gender, baseline alpha-fetoprotein, bilirubin and prothrombin were significantly associated with the risk of HCC occurrence. Among 73 deaths, 61 had a recorded cause and 27 were directly attributable to liver disease. At two years, OS, EFS and cumulative incidences of liver-related deaths were 93% (95% CI 90.5–95.4), 80.3% (95% CI 76.9–83.9), and 3.2% (95% CI 1.6–4.8) respectively. Conclusion: This large prospective cohort incompletely representative of the whole population with alcoholic cirrhosis showed: a) an annual incidence of HCC of up to 2.9 per 100 patient-years, suggesting that surveillance might be cost effective in these patients; b) a high proportion of HCC detected within the Milan criteria, but only one-half of detected HCC cases were referred for curative treatments; c) a two-year mortality rate of up to 7%. Lay summary: Cirrhosis is a risk factor for primary liver cancer, leading to recommendations for periodic screening. However, for alcohol-related liver disease the rational of periodic screening for hepatocellular carcinoma (HCC) is controversial, as registry and databased studies have suggested a low incidence of HCC in these patients and highly competitive mortality rates. In this study, a large cohort of patients with biopsy-proven alcoholic cirrhosis prospectively screened for HCC demonstrated a high annual incidence of HCC (2.9%) and a high percentage of small cancers theoretically eligible for curative treatment. This suggests that patients with liver disease related to alcohol should not be ruled out of screening., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2017

33. Baseline serum ferritin is an independent predictive factor of mortality in patients with chronic hepatitis C after long term follow-up

Author

Romain Moirand, L. Legros, Charlotte Pronier, I. Renard, Z. B. Ali, Valérie Thibault, Dominique Guyader, Caroline Jezequel, Edouard Bardou-Jacquet, Thomas Uguen, Caroline Le Lan, A F Rabot, Christian Michelet, P. Houssel-Debry, CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des maladies du foie, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Centre Hospitalier Universitaire [Rennes], Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des maladies du foie [CHU Rennes], and Centre Hospitalier Universitaire [Rennes]

Subjects
medicine.medical_specialty, Long term follow up, health care facilities, manpower, and services, education, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Chronic hepatitis, Internal medicine, Medicine, In patient, Baseline (configuration management), Serum ferritin, health care economics and organizations, 030304 developmental biology, 0303 health sciences, Hepatology, business.industry, social sciences, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Predictive factor, 030211 gastroenterology & hepatology, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

International audience; International Liver Congress / 52nd Annual Meeting of the European-Association-for-the-Study-of-the-Liver, Amsterdam, Netherland, April 2014

Published
2017

34. Worse Outcomes of Patients With HFE Hemochromatosis With Persistent Increases in Transferrin Saturation During Maintenance Therapy

Author

Pascal Guggenbuhl, Romain Moirand, Dominique Guyader, Caroline Jezequel, Jeff Morcet, Fabrice Lainé, Edouard Bardou-Jacquet, Yves Deugnier, CHU Pontchaillou [Rennes], Foie, métabolismes et cancer, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] ( CIC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Comite de Recherche Clinique et Translationnelle (CORECT) of the University Hospital of Rennes, Association Fer et Foie, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Serum, 0301 basic medicine, Longitudinal study, Time Factors, Gastroenterology, Tertiary Care Centers, Maintenance therapy, Longitudinal Studies, Aged, 80 and over, biology, Transferrin, Middle Aged, 3. Good health, Treatment Outcome, Female, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, Hemochromatosis, Hepcidin Deficiency, Adult, medicine.medical_specialty, Adolescent, Arthropathy, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Hemochromatosis Protein, Aged, Hepatology, Transferrin saturation, business.industry, Iron Regulation, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Odds ratio, medicine.disease, Confidence interval, Surgery, Ferritin, Treatment, 030104 developmental biology, Ferritins, biology.protein, Joints, business, Body mass index
Abstract

International audience; BACKGROUND and AIMS: Even if patients with hemochromatosis maintain low serum levels of ferritin, they still have an increased risk of general and joint symptoms, which reduce quality of life. This could be related to persistently increased transferrin saturation. We assessed whether duration of exposure to increased transferrin saturation during maintenance therapy is associated with more severe general and joint symptoms.METHODS: We performed a longitudinal cohort study of 266 individuals homozygous for the C282Y substitution in HFE, seen at a tertiary reference center in Rennes, France, and followed for 3 or more years after initial iron removal. Serum ferritin and transferrin saturation were measured at the same time points; values were used to calculate duration of exposure to serum ferritin 50 mu g/L or more (FRT50exp) and to determine transferrin saturation 50% or greater (SAT50exp). Clinical and biochemical follow-up data were recorded from log books completed during maintenance therapy. The primary outcome was change in general and joint symptoms, determined from answers to a self-administered questionnaire.RESULTS: Patients were followed for 13.5 +/- 5.9 years. FRT50exp (3.2 +/- 3.5 years) and SAT50exp (4.5 +/- 3.4 years) values correlated (r = 0.38; P less than .0001), but each associated with different variables in multivariate analysis. We found independent associations, regardless of follow-up time, between SAT50exp >= 6 years and worsened joint symptoms (odds ratio [OR], 4.19; 95% confidence interval [CI], 1.88-9.31), and between SAT50exp >= 6 years and decreased athletic ability (OR, 2.35; 95% CI, 1.16-4.73). SAT50exp >= 8 years associated independently with decreased work ability (OR, 3.20; 95% CI, 1.40-7.30) and decreased libido (OR, 3.49; 95% CI, 1.56-7.80).CONCLUSIONS: In a longitudinal study of patients treated for hemochromatosis, we associated duration of exposure to increased transferrin saturation (longer than 6 years) with more severe general and joint symptoms. Maintenance of serum levels of ferritin at 50 mu g/L or less does not indicate control of transferrin saturation, so guidelines on the management of hemochromatosis require revision.

Published
2017

35. The iron reabsorption index

Author

Edouard Bardou-Jacquet, Fabrice Lainé, Romain Moirand, Ghislain Manet, Yves Deugnier, Jeff Morcet, Jean-Paul Sinteff, Michèle Perrin, fer et métabolismes, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Foie, métabolismes et cancer, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de l'information médicale, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de l'information médicale [CHU Rennes], CHU Pontchaillou [Rennes], and Lecoupe-Grainville, Marie

Subjects
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, Adolescent, phenotype, Physiology, Context (language use), hemochromatosis, Cohort Studies, Hemoglobins, Young Adult, 03 medical and health sciences, iron, 0302 clinical medicine, Maintenance therapy, medicine, Humans, Hemochromatosis Protein, Hemochromatosis, Aged, Hepatology, Reabsorption, business.industry, phlebotomy, Histocompatibility Antigens Class I, Gastroenterology, Membrane Proteins, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, Phlebotomy, medicine.disease, Phenotype, Pathophysiology, 3. Good health, Amino Acid Substitution, 030220 oncology & carcinogenesis, Ferritins, Cohort, Immunology, Female, 030211 gastroenterology & hepatology, business, absorption, management, Follow-Up Studies
Abstract

International audience; BACKGROUND: The current phenotypic descriptors of high Fe gene hemochromatosis are hardly specific and time dependent in a context of highly variable expressivity. We hypothesized that the rate of iron removed during maintenance therapy and corresponding to the iron reabsorption index (IRI) could be patient specific and may then represent a new useful phenotypic marker. AIM: The present study aimed to describe IRI with respect to its phenotypic specificity and to its potential usefulness. METHODS: We studied a cohort of 316 p.Cys282Tyr homozygous patients with stable low serum ferritin levels on maintenance therapy for at least 12 months. Characteristics at diagnosis, date and volume of phlebotomies, and parameters of iron metabolism throughout maintenance therapy were determined. RESULTS: IRI ranged from 1.3 to 6.1 mg/day (median: 2.44). It was lower in women (difference: 1.26 mg/day), mainly explained by physiological blood loss, weight, and alcohol consumption. IRI was correlated to iron burden and fibrosis stage at diagnosis, was stable over time (variation: 11.5%), and depended on serum ferritin level during therapy. CONCLUSION: Its independence from disease duration, its stability, its wide distribution, and its significant correlation with iron burden markers make IRI a valuable potential phenotypic indicator of the daily iron overabsorption in hemochromatosis. Moreover, IRI provides a conceptual frame for empiric adaptation of maintenance therapy.

Published
2013

36. Generalized anxiety disorder is under-recognized in clinical practice in patients with alcohol dependence in France

Author

Romain Moirand, Didier Robin, Dominique Drapier, Violaine Charriau, M'hammed Elyakoubi, and Bruno Millet

Subjects
Adult, Male, medicine.medical_specialty, Health (social science), Generalized anxiety disorder, media_common.quotation_subject, Prevalence, Comorbidity, Anxiety, Toxicology, Biochemistry, Behavioral Neuroscience, Bias, medicine, Humans, Psychiatric hospital, Prospective Studies, Psychiatry, Retrospective Studies, media_common, Mental Disorders, Alcohol dependence, General Medicine, Middle Aged, medicine.disease, Anxiety Disorders, Confidence interval, Alcoholism, Neurology, Female, France, Worry, medicine.symptom, Psychology
Abstract

Generalized Anxiety Disorder (GAD) is a frequent disabling disorder that often occurs with alcohol dependence. However comorbidity between substance use disorders and psychiatric disorders is often under-diagnosed. This study tried to evaluate an under-recognition of GAD by clinicians in alcoholic inpatients. Two groups of alcohol-dependent inpatients, hospitalized in the same non-academic psychiatric hospital in France, were included. The first group (Group 1) (n = 205) was included retrospectively within all patients hospitalized for alcohol dependence from may to November 2007. A record review was performed to determine the number of GAD (and other psychiatric disorders) diagnosis which was reported on these files by the clinicians. The second group (Group 2) (n = 199) was included prospectively from May to November 2008. GAD diagnosis was screened with the Worry and Anxiety Questionnaire and then confirmed with the Mini International Neurodiagnostic Interview. The two groups were similar in terms of social and demographic variables. GAD prevalence rate was significantly higher in Group 2 (30.7% with Confidence Interval [0.242; 0.371]) than in Group 1 (2.4% with Confidence Interval [0.003; 0.045]). This study confirms our hypothesis of an under-recognition of GAD by clinicians in alcohol dependant inpatients. It also confirms the high prevalence rate of comorbidity between alcohol dependence and GAD.

Published
2013

37. Acoustic radiation force impulse imaging for assessing liver fibrosis in alcoholic liver disease

Author

Antonia Le Gruyer, Edouard Bardou-Jacquet, Anita Kiani, Fabrice Lainé, Bruno Turlin, Vanessa Brun, Ludivine Legros, Jeff Morcet, Yves Gandon, Sophie Michalak, Romain Moirand, Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Laboratoire de Pathologie Cellulaire et Tissulaire, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Adult, Male, Alcoholic liver disease, medicine.medical_specialty, Acoustic radiation force impulse, Biopsy, [SDV]Life Sciences [q-bio], Severity of Illness Index, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Liver Cirrhosis, Alcoholic, Predictive Value of Tests, medicine, Humans, Prospective Studies, Non-invasive, Prospective cohort study, Acoustic radiation force impulse imaging, medicine.diagnostic_test, business.industry, Gastroenterology, Reproducibility of Results, General Medicine, Middle Aged, medicine.disease, 3. Good health, Liver, ROC Curve, Liver biopsy, Predictive value of tests, Area Under Curve, Elasticity Imaging Techniques, Prospective Study, 030211 gastroenterology & hepatology, Female, Elastography, Radiology, business, Nuclear medicine
Abstract

International audience; AIM: To evaluate the performance of elastography by ultrasound with acoustic radiation force impulse (ARFI) in determining fibrosis stage in patients with alcoholic liver disease (ALD) undergoing alcoholic detoxification in relation to biopsy. METHODS: Eighty-three patients with ALD undergoing detoxification were prospectively enrolled. Each patient underwent ARFI imaging and a liver biopsy on the same day. Fibrosis was staged according to the METAVIR scoring system. The median of 10 valid ARFI measurements was calculated for each patient. RESULTS: Sixty-nine males and thirteen females (one patient excluded due to insufficient biopsy size) were assessed with a mean alcohol consumption of 132.4 ± 128.8 standard drinks per week and mean cumulative year duration of 17.6 ± 9.5 years. Sensitivity and specificity were respectively 82.4% (0.70-0.95) and 83.3% (0.73-0.94) (AUROC = 0.87) for F ≥ 2 with a cut-off value of 1.63m/s; 82.4% (0.64-1.00) and 78.5% (0.69-0.89) (AUROC = 0.86) for F ≥ 3 with a cut-off value of 1.84m/s; and 92.3% (0.78-1.00] and 81.6% (0.72-0.90) (AUROC = 0.89) for F = 4 with a cut-off value of 1.94 m/s. CONCLUSION: ARFI is an accurate, non-invasive and easy method for assessing liver fibrosis in patients with ALD undergoing alcoholic detoxification

Published
2016

38. Pharmacotherapy for Alcohol Dependence: The 2015 Recommendations of the French Alcohol Society, Issued in Partnership with the European Federation of Addiction Societies

Author

Alain Rigaud, Henri-Jean Aubin, Romain Moirand, Maurice Dematteis, Benjamin Rolland, Claudine Gillet, Karl Mann, Corine Dano, François Paille, Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Reims (CHU Reims), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Universität Mannheim, Santé mentale et santé publique (SMSP - U1178), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), French Department of Health (DGS), Pharmaceutical Companies (D&A Pharma, Ethypharm, Lundbeck and Merck Serono), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, CNRS, Inserm, Université de Lille, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universität Mannheim [Mannheim], Department of movement disorders and neurology & University of Lille Department of medical pharmacology & INSERM U1171, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire d'Angers ( CHU Angers ), PRES Université Nantes Angers Le Mans ( UNAM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Santé mentale et santé publique ( SMSP - U1178 ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), AUBIN, HENRI JEAN, Troubles cognitifs vasculaires et dégénératifs, Université de Lille, Sciences et Technologies, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Nancy, Université de Rennes 1 (UR1) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hypoxie et physiopathologies cardiovasculaire et respiratoire, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF), Pôle Pluridisciplinaire de Médecine, CHU Grenoble - Hôpital Michallon, Santé mentale et santé publique (SMSP), and Université Paris-Sud - Paris 11 (UP11) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - AP-HP Hôpital Necker - Enfants Malades [Paris]

Subjects
Male, Addiction medicine, Alcohol, Alcoholism, France, Guidelines, Pharmacotherapy, Primary care, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 0302 clinical medicine, Pregnancy, Secondary Prevention, Pharmacology (medical), 030212 general & internal medicine, Societies, Medical, media_common, Addiction medicine, Alcohol detoxification, Primary care, 3. Good health, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Alcoholism, Acamprosate, Female, Pharmacotherapy, Guidelines, Alcohol, France, medicine.drug, medicine.medical_specialty, media_common.quotation_subject, Relapse prevention, 03 medical and health sciences, Physiology (medical), medicine, Humans, Psychiatry, Letters to the Editor, Pharmacology, Delirium tremens, [ SDV ] Life Sciences [q-bio], business.industry, Alcohol dependence, Off-Label Use, Abstinence, medicine.disease, Pregnancy Complications, business, 030217 neurology & neurosurgery, Clinical Guidelines, Alcohol Abstinence, Alcohol Deterrents
Abstract

International audience; BACKGROUND: The latest French good practice recommendations (GPRs) for the screening, prevention, and treatment of alcohol misuse were recently published in partnership with the European Federation of Addiction Societies (EUFAS). This article aims to synthesize the GPRs focused on the pharmacotherapy of alcohol dependence.METHODS: A four-member European steering committee defined the questions that were addressed to an 18-member multi-professional working group (WG). The WG developed the GPRs based on a systematic, hierarchical and structured literature search and submitted the document to two review processes involving 37 French members from multiple disciplines and 5 non-French EUFAS members. The final GPRs were graded A, B, or C, or expert consensus (EC) using a reference recommendation grading system. RESULTS: - The treatment of alcohol dependence consists of either 1) alcohol detoxification / abstinence maintenance programs or 2) drinking reduction programs. - The therapeutic objective is the result of a decision made jointly by the physician and the patient.- Benzodiazepines (BZDs) are the first-line medication for detoxification (GRADE A). - BZD dosing should be guided by regular clinical monitoring (GRADE B). - Residential detoxification is more appropriate for patients with a history of seizures, delirium tremens, unstable psychiatric comorbidity, or another associated substance use disorder (GRADE B). - BZDs are only justified beyond a one-week period in the case of persistent withdrawal symptoms, withdrawal events or associated BZD dependence (GRADE B). - BZDs should not be continued for more than four weeks (GRADE C). - The dosing and duration of thiamine (vitamin B1) during detoxification should be adapted to nutritional status (EC). - Medications for relapse prevention should be automatically associated with adapted psychosocial support (GRADE A). - Acamprosate and naltrexone are the first-line options for relapse prevention (GRADE A). - Disulfiram can be proposed as second-line treatment in patients who are correctly informed and adequately supervised (EC).- Medications for reducing alcohol consumption are only indicated in dependent individuals (EC). - Nalmefene is indicated as a first-line treatment for reducing alcohol consumption (GRADE A). - The second-line prescription of baclofen, up to 300 mg/d, to prevent relapse or reduce drinking should be carried out according to the “temporary recommendation for use” (TRU) issued by the French Health Agency (EC).- Abstinence is recommended throughout pregnancy (EC).- If medically‐assisted withdrawal is necessary during pregnancy, BZD use is recommended (GRADE B).- No medication other than those for alcohol withdrawal should be initiated in pregnant or breastfeeding women (EC).- In a stabilized pregnant patient taking medication to support abstinence, the continuation of the drug should be considered on a case‐by‐case basis, weighing the benefit/risk ratio. Only disulfiram should be always stopped, given the unknown risks of the antabuse effect on the fetus (EC).- First‐line treatments to help maintain abstinence or reduce drinking are off-label for people under 18 years of age and should thus be considered on a case-by-case basis after the repeated failure of psychosocial measures alone (EC).- Short-half-life BZDs should be preferred for the detoxification of elderly patients (GRADE B).- The initial doses of BZDs should be reduced by 30 to 50% in elderly patients (EC).- In patients with chronic alcohol-related physical disorders, the goal of abstinence is recommended (EC)- Any antidepressant or anxiolytic medication should be introduced after a psychiatric reassessment after 2-4 weeks of alcohol abstinence or low-risk use (GRADE B).- A smoking cessation program should be offered to any smokers involved in an alcohol treatment program (GRADE B).

Published
2016

39. Ethanol Effect on Cell Proliferation in the Human Hepatoma HepaRG Cell Line: Relationship With Iron Metabolism

Author

Olivier Loréal, Romain Moirand, Thi Hong Tuoi Do, Martine Ropert, Isabelle Cannie, François Gaboriau, Pierre Brissot, and Gérard Lescoat

Subjects
chemistry.chemical_classification, 0303 health sciences, Cell growth, Medicine (miscellaneous), Transferrin receptor, Biology, Toxicology, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, medicine.anatomical_structure, chemistry, Biochemistry, Transferrin, Hepatocyte, biology.protein, medicine, Viability assay, Ceruloplasmin, Ethanol effect, 030217 neurology & neurosurgery, 030304 developmental biology, Soluble transferrin receptor
Abstract

BACKGROUND: Alcoholism increases the risk of cirrhosis and/or hepatocellular carcinoma development. Iron, like ethanol, modulates the cell growth. However, the relationship between alcohol and iron toward hepatocyte proliferation has not been clearly elucidated. The purpose of this study was to evaluate, in the human HepaRG cell line model, the impact of ethanol on hepatocyte proliferation in relation to modulations of iron metabolism and the protective effect of iron metabolism manipulation by chelators in alcohol liver diseases. METHODS: The human hepatoma HepaRG cell line model was used. Cell viability was determined by measuring succinate dehydrogenase activity, total protein level by the Bradford method. DNA synthesis was evaluated by [(3)H]-methyl thymidine incorporation. Cytotoxicity was studied by release of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) in culture medium and apoptosis by measuring caspase 3/7 activity. Gene expression was analyzed by RT-qPCR. Total iron, soluble transferrin receptor, and ferritin levels were, respectively, measured by colorimetrical, immuno-nephelometrical, and immuno-turbidimetrical methods. Intracellular iron uptake and accumulation was examined by radionuclide (55)Fe (III) measurement and Perls staining. RESULTS: Results showed that ethanol decreased all the parameters associated with HepaRG cell proliferation (cell viability, total protein levels, and DNA synthesis) in a dose- and time-dependent manner. This effect was accompanied by cytotoxicity and apoptosis as evaluated by a significant increase in extracellular enzymes (LDH, AST, ALT) and caspase 3/7 activity, respectively. Ethanol exposure was accompanied by an increased cellular iron uptake, together with increased expression of genes involved in iron transport and storage such as l-ferritin, Divalent Metal transporter 1, transferrin, transferrin receptor 1, and ceruloplasmin. Ethanol impact was intensified by iron-citrate and decreased by iron chelators when added to the culture medium. CONCLUSIONS: The results indicated that (i) ethanol-induced iron metabolism dysfunction could be one of the underlying mechanisms of ethanol antiproliferative effect and (ii) exogenous iron may accentuate ethanol hepatoxicity. These data suggest that iron metabolism manipulation by chelators may be a useful therapeutic approach in alcohol-related liver diseases.

Published
2010

40. Marqueurs biologiques de l'alcoolisme

Author

Olivier Loréal, P. Brissot, Romain Moirand, A Le Gruyer, and C Le Lan

Subjects
business.industry, Medicine, business, Molecular biology
Published
2010

41. Iron induction of ferritin synthesis and secretion in human hepatoma cell (Hep G2) cultures

Author

Yves Deugnier, Olivier Loréal, Romain Moirand, Nicole Pasdeloup, J. F. Dezier, Pierre Brissot, and Gérard Lescoat

Subjects
Nitrilotriacetic Acid, Carcinoma, Hepatocellular, Iron, Stimulation, In Vitro Techniques, Ferric Compounds, Albumins, Tumor Cells, Cultured, medicine, Humans, Prealbumin, Secretion, chemistry.chemical_classification, Hepatology, biology, Liver Neoplasms, Transferrin, Albumin, Molecular biology, Stimulation, Chemical, Hep G2, Ferritin, Transthyretin, medicine.anatomical_structure, chemistry, Biochemistry, Hepatocyte, Ferritins, biology.protein
Abstract

In order to determine if iron was able to stimulate specifically ferritin synthesis and secretion in transformed human hepatocytes in culture, human hepatoma cell (HepG2) cultures were submitted to increasing doses of ferric nitrilotriacetate. Iron uptake by the cells was demonstrated by incorporation of 59 Fe and the staining method of Perls. The following results were obtained: 1. iron incorporation within the hepatocytes increased as a function of culture time; 2. during the first 24 h of treatment, ferritin synthesis increased progressively, in parallel to the iron uptake; 3. a dose-dependent significant stimulation of ferritin synthesis and secretion were observed when the medium iron concentration increased from 5 to 20 mumol/l; 4. albumin, transthyretin and transferrin secretions were unaffected. These data demonstrated that, in our hepatocyte culture model, iron load increased the expression of ferritin in a highly specific manner.

Published
2008

42. Pharmacokinetics of Sirolimus (Rapamycin) in Subjects With Severe Hepatic Impairment

Author

Romain Moirand, Alain Patat, Virginia Parks, James J. Zimmerman, and Kyle Matschke

Subjects
Male, medicine.medical_specialty, Administration, Oral, Pharmacology, Severity of Illness Index, Gastroenterology, Pharmacokinetics, Dose adjustment, Internal medicine, Cholecystitis, Humans, Medicine, Pharmacology (medical), In patient, Aspartate Aminotransferases, Child-Pugh - Grade, Aged, Sirolimus, medicine.diagnostic_test, business.industry, Liver Diseases, Hepatic impairment, Matched control, Alanine Transaminase, Bilirubin, Middle Aged, Alkaline Phosphatase, Therapeutic drug monitoring, Area Under Curve, Case-Control Studies, Creatinine, Female, business, Immunosuppressive Agents, Half-Life, medicine.drug
Abstract

Nine subjects with severe hepatic impairment (Child-Pugh grade C) and 9 healthy matched control subjects were given a single 15-mg dose of sirolimus by oral solution. Increases (P < or = .002) in mean whole-blood sirolimus t(1/2) (168%), AUC(0-infinity) (210%), and MRT(oral) (261%), together with a decrease (P = .001) in CL/F (-67%), were observed in subjects with severe hepatic impairment compared with healthy matched controls. Sirolimus pharmacokinetic data in Child-Pugh grade A (n = 13, mild) and B (n = 5, moderate) subjects from a previous identically designed study were available for an inter-study comparison. Overall, mean t(1/2), weight-normalized AUC, and MRT(oral) increased steadily, whereas mean CL/F decreased steadily, with increasing degrees of hepatic impairment. CL/F showed large intersubject variabilities within subject types and extensive overlap among the subject types. The results of this study suggest that an initial sirolimus dose reduction of approximately 60% is appropriate in patients with acute severe hepatic impairment; this should be followed by further dose adjustment, based on therapeutic drug monitoring, until the trough concentrations have stabilized at sirolimus levels existing prior to the onset of acute liver failure.

Published
2008

43. [Realities of alcohol withdrawal]

Author

François, Paille and Romain, Moirand

Subjects
Ethanol, Central Nervous System Depressants, Humans, Patient Compliance, Alcohol Deterrents, Substance Withdrawal Syndrome
Published
2015

44. [Addiction to alcohol]

Author

François, Paille and Romain, Moirand

Subjects
Psychotherapy, Alcoholism, Surveys and Questionnaires, Humans, Algorithms, Biomarkers, Alcohol Deterrents, Alcohol-Induced Disorders
Published
2015

45. Postdetoxification Factors Predicting Alcohol-Related Emergency Room Visits 12 to 24 Months After Discharge: Results from a Prospective Study of Patients with Alcohol Dependence

Author

Romain Moirand, Aymery Constant, Françoise Riou, Caroline Le Lan, Antonia Le Gruyer, École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre Hospitalier Universitaire [Rennes], Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), The study was supported by the funding body of the Rennes University Hospital Addiction Unit, the 'Association Fer et Foie'., Jonchère, Laurent, Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Adult, Male, Emergency Medical Services, Pediatrics, medicine.medical_specialty, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Social Environment, Toxicology, Social support, symbols.namesake, Recurrence, medicine, Emergency medical services, Humans, Prospective Studies, Poisson regression, detoxification, Prospective cohort study, media_common, business.industry, Addiction, Alcohol dependence, Social environment, Middle Aged, Family life, 3. Good health, [SDV] Life Sciences [q-bio], Alcoholism, Psychiatry and Mental health, determinants analysis, emergency room visits, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, symbols, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, prospective study
Abstract

Background Relapse is common in patients with alcohol dependence, even after detoxification. The aims of this prospective study were to investigate changes affecting patients during the first 6 months after discharge from hospitalization for detoxification and to determine the influence of these changes on the likelihood of alcohol-related emergency room (ER) visits in the following 18-month period. Methods The study included 88 patients hospitalized for participation in a detoxification program in the addiction department of a university hospital in Rennes, France. Alcohol consumption, psychiatric symptoms, and life events were investigated by addiction specialists during hospitalization and 6 months afterward. For each patient, the number of alcohol-related ER visits in the last 6 months was prospectively recorded at the hospital 12, 18, and 24 months after hospitalization. The rate ratios of ER visits as a function of sociodemographic variables and changes observed 6 months after discharge were estimated using Poisson regression with autoregressive errors. Results Nearly half of the patients (47.7%) had ER visits in the 12- to 24-month period following discharge. The likelihood of ER visits was higher for patients living with friends/parents and for those with aggravated psychiatric symptoms, negative changes in their family life, and who had a medical follow-up in the 6 months after discharge. In contrast, the likelihood of ER visits was lower for patients living with children and those with improved psychiatric morbidity. Alcohol consumption and psychiatric symptoms at baseline had no significant effect. Conclusions Monitoring changes in psychiatric symptoms and family life early after a detoxification program may help identify patients who are vulnerable to relapse in the subsequent 18-month period. Systematic screening for these changes as early as possible, in combination with appropriate treatment and the establishment of a social support system, could be fundamental in avoiding further relapses and ER visits.

Published
2015

46. Non-invasive assessment of liver fibrosis in C282Y homozygous HFE hemochromatosis

Author

Fabrice Lainé, Marianne Latournerie, Yoann Désille, Yves Deugnier, Romain Moirand, Ludivine Legros, Anne Guillygomarc'h, Dominique Guyader, Caroline Le Lan, Edouard Bardou-Jacquet, Bruno Turlin, Pierre Brissot, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'hépato-gastro-entérologie [Rennes] = Gastroenterology [Rennes], Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], Centre Hospitalier Universitaire [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Biopsy, [SDV]Life Sciences [q-bio], Gastroenterology, Fibrosis, Internal medicine, hyaluronic acid, medicine, Humans, Prospective Studies, Hemochromatosis, Transaminases, liver fibrosis, Hepatology, medicine.diagnostic_test, business.industry, cirrhosis, Homozygote, serum ferritin, Middle Aged, medicine.disease, transient elastography, 3. Good health, Surgery, Liver, ROC Curve, Liver biopsy, Concomitant, Ferritins, Mutation, Elevated transaminases, Elasticity Imaging Techniques, Female, Transient elastography, business, Cohort study
Abstract

International audience; Background & aims - C282Y homozygotes with serum ferritin (SF) levels >1000 μg/L and/or increased serum transaminase levels are at risk of severe F3/F4 fibrosis. Current practical guidelines recommend liver biopsy in such individuals. This prospective observational cohort study aimed to evaluate non-invasive alternative means such as hyaluronic acid (HA) and transient elastography (TE) for the assessment of severe fibrosis in patients with SF >1000 μg/L or elevated transaminases. Methods - Between September 2005 and April 2013, 77 patients diagnosed C282Y homozygotes underwent a liver biopsy because of SF >1000 μg/L and/or increased transaminases according to current guidelines, with concomitant TE. All of them had clinical and biological evaluation, including HA measurement in 52 cases. Results - A total of 19.5% of patients had F3-F4 severe fibrosis. HA was higher in patients with severe fibrosis, but did not accurately predict severe fibrosis. TE was significantly higher in patients with severe fibrosis (17.2 vs. 4.9 kPa; P

Published
2015

47. G08 : Incidence of hepatocellular carcinoma (HCC) and complications in alcoholic compensated cirrhosis. Preliminary results of a multicenter prospective French and belgian cohort (INCA Cirral)

Author

Xavier Amiot, Cendrine Chaffaut, Jean Charles Duclos-Vallée, I. Archambaud, Dominique Roulot, Albert Tran, Eric Nguyen-Khac, Odile Goria, Violaine Ozenne, Romain Moirand, Jean-Pierre Zarski, Nicolas Carbonell, V. de Ledinghen, Stanislas Pol, Sylvie Chevret, Alexandre Louvet, Christophe Moreno, V. Bourcier, Thong Dao, Jean-Marc Perarnau, Jean Henrion, Nathalie Ganne, Frédéric Oberti, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier St. Joseph, Department of Gastroenterology, Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
0303 health sciences, medicine.medical_specialty, Cirrhosis, [ SDV ] Life Sciences [q-bio], Hepatology, 030309 nutrition & dietetics, business.industry, Incidence (epidemiology), [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, medicine.disease, Gastroenterology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Hepatocellular carcinoma, Cohort, medicine, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2015

48. P0709 : Survival of patients infected by chronic hepatitis c and f0f1 fibrosis at baseline after a 15 years follow-up

Author

Romain Moirand, Yoann Désille, Yves Deugnier, C. Lelan, Anne Guillygomarc'h, Dominique Guyader, P. Houssel-Debry, I. Renard, Marianne Latournerie, Edouard Bardou-Jacquet, Caroline Jezequel, Fabrice Lainé, Milieux aquatiques, écologie et pollutions (UR MALY), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Eugène Marquis (CRLCC), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Hepatology, business.industry, [SDV]Life Sciences [q-bio], medicine.disease, Gastroenterology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Chronic hepatitis, Fibrosis, Internal medicine, medicine, 030211 gastroenterology & hepatology, 030212 general & internal medicine, Baseline (configuration management), business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2015

49. Decreased Cardiovascular and Extrahepatic Cancer-Related Mortality In Treated Patients with Mild HFE Hemochromatosis

Author

Edouard Bardou-Jacquet, Fabrice Lainé, Romain Moirand, Dominique Guyader, Jean-François Viel, Ghislain Manet, Jeff Morcet, Michèle Perrin, Anne-Marie Jouanolle, Yves Deugnier, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génétique moléculaire, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes], Service de santé publique et d'épidémiologie, CHU Pontchaillou [Rennes], Cadieu, Muriel, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes]

Subjects
medicine.medical_specialty, Survival, Population, Cardio-vascular disease, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Iron overload, education, Hemochromatosis, Cancer, education.field_of_study, Hepatology, business.industry, Hazard ratio, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Confidence interval, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Surgery, Standardized mortality ratio, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, HFE, business
Abstract

International audience; Background & aims - Mortality studies in patients with hemochromatosis give conflicting results especially with respect to extrahepatic causes of death. Our objective was to assess mortality and causes of death in a cohort of patients homozygous for the C282Y mutation in the HFE gene, diagnosed since the availability of HFE testing. Methods - We studied 1085 C282Y homozygotes, consecutively diagnosed from 1996 to 2009, and treated according to current recommendations. Mortality and causes of death were obtained from death certificates and compared to those of the general population. Standardized mortality ratios (SMRs) were used to assess specific causes of death and the Cox model was used to identify prognostic factors for death. Results - Patients were followed for 8.3±3.9 years. Overall the SMR was the same as in the general population (0.94 CI: 0.71-1.22). Patients with serum ferritin⩾2000 μg/L had increased liver-related deaths (SMR: 23.9 CI: 13.9-38.2), especially due to hepatic cancer (SMR: 49.1 CI: 24.5-87.9). Patients with serum ferritin between normal and 1000 μg/L had a lower mortality than the general population (SMR: 0.27 CI: 0.1-0.5), due to a decreased mortality, related to reduced cardiovascular events and extrahepatic cancers in the absence of increased liver-related mortality. Age, diabetes, alcohol consumption, and hepatic fibrosis were independent prognostic factors of death. Conclusions - In treated HFE hemochromatosis, only patients with serum ferritin higher than 2000 μg/L have an increased mortality, mainly related to liver diseases. Those with mild iron burden have a decreased overall mortality in relation to reduced cardiovascular and extrahepatic cancer-related events. These results support a beneficial effect of early and sustained management of patients with iron excess, even when mild.

Published
2015

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