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The three-fold objective of this study was to describe the opinions, the population served, and tools used for the management of nonalcoholic fatty liver disease (NAFLD) by French hepato(gastro)enterologists (HGEs).Seventy-five French HGEs working in hospitals or in private practice, who regularly managed patients with NAFLD, completed three questionnaires: one about their opinions about disease management, one on the 10 first patients with NAFLD they saw in February 2020, and the third about the first five patients meeting the 2016 European Association for the Study of the Liver criteria for specialist referral.Management of NAFLD was seen as challenging, complex, time-consuming, and frustrating. Available treatments were considered to be unsatisfactory by most participants. In the whole population studied (671 patients), 41% were obese, 50% overweight, 49% had type 2 diabetes, 61% dyslipidemia, 51% arterial hypertension, 57% nonalcoholic steato-hepatitis (NASH), 37% advanced fibrosis, and 19% cirrhosis. In the subgroup of 313 patients needing specialist referral, the use of liver biopsy was low (30%) and decreasing, whereas vibration-controlled transient elastometry was high (66%) and increasing; blood fibrosis tests were rarely used. NASH was usually diagnosed without liver biopsy. Nutritional counseling was provided to 3/4 patients, physical activity counseling in 1/5. A personalized therapeutic project was defined in less than one-third of patients. Ursodeoxycholic acid and vitamin E were used in a minority of patients.The management of NAFLD is not considered satisfactory by French HGE who care for a relatively severe population. Noninvasive assessment of fibrosis and multidisciplinary management should be improved.

Introduction Sofosbuvir is the first directly-acting antiviral for the treatment of hepatitis C virus. First, the regimens were combinations with sofosbuvir+ribavirin (SR) or with sofosbuvir+ribavirin and pegylated-interferon α-2a (SPR) with cure rates around 90%. The aim of this study was to report the results of these combinations in 'real-life' in France. Materials and methods Main features of patients treated with SR or SPR in 24 hospitals were collected. Undetectable hepatitis C virus week 12 viral load after treatment defined sustained virological response (SVR12). Statistics were performed using StatView software for descriptive analysis and χ for the sub-groups comparisons. Results Two hundred and eleven patients were analyzed. The average age was 56.1. One hundred and seventy-one (89%) patients had a fibrosis score of at least 3. Seventy-nine patients were infected by a genotype 1 (G1). One hundred and thirteen patients were treated with SR and 95 with SPR. In naive patients: with SPR for 12 weeks, SVR12 was 93% in G1, 100% in G3 and 83% in G4. With SR for 12 weeks, SVR12 was 100% in G2 patients (6/6). The safety of these regimens was satisfactory with only two patients who had to stop P due to severe side effects. Multivariate analysis shows a higher SVR in SPR versus SR (odds ratio = 1.28; P = 0.05) and in G2 or G3 versus others (odds ratio = 1.56; P = 0.04). Moreover, Child-Pugh score B or C (P = 0.02), platelets count under 100G/l (P = 0.05) or a past event of ascites (P = 0.04) was independently associated with less SVR. Conclusion This multicenter large study confirms the good results of SR for 12 weeks in G2 naive patients. Finally, a decompensated cirrhosis, a past event of ascites and a baseline low platelet count were strongly associated with poor response.

BACKGROUND AND AIMS To assess the characteristics, care, treatment response, and outcomes of primary biliary cholangitis (PBC) patients recently followed-up by hepato-gastroenterologists in various French and Belgian healthcare settings. METHODS This retrospective cohort study included patients with PBC who recently visited 79 hepato-gastroenterologists in France and Belgium. Data were collected at the time of diagnosis and at last visit and were compared according to biochemical response (BR) to ursodeoxycholic acid (UDCA) (BR), using Paris I-II criteria, and clinical outcomes. RESULTS A total of 436 patients (mean age at diagnosis 57 years, 88% females, median follow-up 5.2 years) were included. Liver biopsy, transient elastography, or none of these two procedures were performed at baseline in 216 (50%), 194 (45%), and 107 (25%) patients, respectively. Late-stage disease (histological stage III or IV, or transient elastography ≥9.6 kPa, or bilirubin >17 µM and albumin

BACKGROUND Recent data suggest that alcohol-related hepatocellular carcinoma (HCC) is diagnosed at a later stage. The aim of this study was to compare HCC characteristics and outcomes in an alcohol-related group (group A) and a non-alcohol-related group (group NA). METHODS A total of 1207 patients with newly diagnosed HCC were prospectively included between May 2008 and October 2009. Patients with multiple causes (alcohol plus another cause) were excluded. Patients were followed every year for 5 years. Recorded variables, including etiologies were tested as prognostic factors of survival in a multivariate Cox model after adjustments for a lead-time bias. RESULTS In all, 894 patients were analyzed: 582 (65.1%) were in group A, and 312 (34.9%) were in group NA. Alcohol-related HCC was more likely to be diffuse and detected in patients with a worse performance status and worse liver function. After adjustments for a lead-time bias, the median overall survival (OS) was 9.7 and 5.7 months in groups NA and A, respectively (P = .0002), and 5.8 and 5.0 months in alcohol-abstinent and alcohol non-abstinent groups, respectively (P = .09). The prognostic role of alcohol disappeared when survival was assessed at each Barcelona Clinic Liver Cancer (BCLC) stage. Patients with HCC detected during a cirrhosis follow-up program (n = 199 [22.3% of the whole cohort]) had increased lead time-adjusted median OS in comparison with patients with HCC diagnosed incidentally (11.7 vs 5.4 months; P < .0001). CONCLUSIONS In comparison with patients with non-alcohol-related HCC, patients with alcohol-related HCC have reduced OS, mainly because of worse liver function and tumor characteristics at diagnosis, as attested by similar survival within each BCLC stage. Cancer 2018;124:1964-72. © 2018 American Cancer Society.

Background & Aims The Baveno VI consensus meeting concluded that an early transjugular intra-hepatic porto-systemic shunt (TIPS) must be considered in high-risk patients with cirrhosis, presenting with variceal bleeding (VB) (Child B + active bleeding at endoscopy or Child C10-13 patients). Whether this therapeutic approach is feasible in a real-life setting remains unclear. The aim of this study was to determine (i) the proportion of patients eligible for early-TIPS among patients with cirrhosis and VB, (ii) the proportion of these patients who underwent early-TIPS placement and the main reasons for discarding TIPS, and (iii) the outcomes of patients who experienced early-TIPS placement. Methods A large, national, prospective, multicentre audit of academic and non-academic centres, in which all French centres recruiting patients with gastrointestinal bleeding were invited to participate. All consecutive patients with cirrhosis and portal hypertension-related bleeding were included. Results A total of 964 patients were included (58 centres: 26 academic, 32 non-academic; patient characteristics: male sex 77%; age 59.6 ± 12.1 years; aetiologies of cirrhosis (alcoholic 67%, viral 15%, other 18%); source of bleeding (oesophageal varices 80%, gastric varices 11%, other 9%); active bleeding at endoscopy 34%; Child A 21%, B 44%, C 35%. Overall, 35% of the patients were eligible for early-TIPS, but only 6.8%, displaying less severe cirrhosis underwent early-TIPS placement. The main reason for discarding TIPS was a lack of availability. The actuarial probability of survival at one year was significantly increased in early-TIPS patients (85.7 ± 0.07% vs. 58.9 ± 0.03%, p = 0.04). The severity of liver disease was the only parameter independently associated with improved one-year survival. Conclusion In this real-life study, one-third of the patients with cirrhosis, admitted for VB fulfilled the criteria for early-TIPS placement, whereas only 7% had access to TIPS. TIPS was restricted to patients displaying less severe cirrhosis. The severity of liver disease was the only parameter that influenced survival. Lay summary Bleeding from oesophageal or gastric varices is a severe complication of cirrhosis, related to an increased pressure in the portal vein perfusing the liver. Some patients are described as “severe”, either because their liver disease is already severe, or because the bleeding is very important. Those patients could benefit from a prothesis, placed inside the liver by an interventional radiologist, aiming to decrease the pressure in the portal vein, just after the control of bleeding by medications and endoscopic treatment. New studies are warranted to demonstrate a real beneficial effect of this therapeutic attitude, which is not adopted in real-life practice, as shown by this national French audit of practice.

Summary Aims To determinate the topographical distribution of key diagnostic histological features of lymphocytic colitis (LC) and collagenous colitis (CC) and to establish what correlations may exist between the histological findings and the causes and severity of MC. Patients and methods Patients with MC were included in a prospective multicentre French study from September 2010 to October 2012. MC was diagnosed by performing total colonoscopy with multiple biopsies of the rectum and colon collected in separate jars and analyzed separately for each site (descending and sigmoid colon, transverse colon, ascending colon). CC was defined as a subepithelial collagen layer > 10 μm thick and LC as an intraepithelial lymphocyte (IEL) count > 20 lymphocytes per 100 epithelial cells without any associated thickening of the subepithelial collagen. Results Ninety-five patients, 69 with LC 26 and with CC, were included in the analysis. The sensitivity of the biopsies for diagnosing MC was maximum in the transverse colon and minimum in the rectum. Rectal and left colonic biopsies resulted in the diagnosis of CC and CL in 93% and 94% of cases, respectively. All the remaining cases of MC were diagnosed by performing additional biopsies beyond the splenic flexure. In patients with LC, a higher rate of IELs was associated with the absence of abdominal pain (P = 0.01) and a shorter duration of diarrhea (P = 0.001). In patients with CC, a lower level of collagen thickness in the basement membrane was associated with the presence of an autoimmune disease (P = 0.02). Conclusion More than 90% of cases of microscopic colitis were diagnosed in this study by performing rectal and left colonic biopsies.

The aim of this study was to determine the mortality and re-bleeding rates, and the risk factors involved, in a cohort of patients with previous diverticular bleeding (DB).In 2007, data on 2462 patients with lower gastrointestinal (GI) bleeding were collected prospectively at several French hospitals. We studied the follow-up of patients with DB retrospectively. The following data were collected: age, mortality rates and re-bleeding rates, drug intake, surgery and comorbidities.Data on 365 patients, including 181 women (mean age 83.6 ± 9.8 years) were available. The median follow-up time was 3.9 years (IQR 25-75: 1.7-5.4). Of these, 148 patients died (40.5%). Among the 70 patients (19.2%) who had at least one re-bleeding episode, nine died and three underwent surgical procedures. Anticoagulation and antiplatelet therapy was discontinued in 70 cases (19.2%). The independent risk factors contributing to mortality were age 80 years (HR = 3.18 (2.1-4.9);In this cohort, the rates of mortality and DB re-bleeding after a median follow-up time of 3.9 years were 19.2% and 40.5%, respectively. The majority of the deaths recorded were not due to re-bleeding.

Introduction and aim Data on the efficacy and tolerance of interferon-free treatment in chronic hepatitis C (CHC) in elderly patients are limited in phase II-III trials. Material and methods A prospective cohort of adult patients with CHC treated in French general hospitals. Results Data from 1,123 patients, distributed into four age groups, were analyzed. Of these, 278 were > 64 years old (fourth quartile) and 133 were > 73 years old (tenth decile). Elderly patients weighed less, were more frequently treatment-experienced women infected with genotype 1b or 2, while they less frequently had genotype 3 or HIV coinfection, but had more frequent comorbidities and drug consumption. Half of the patients had cirrhosis, whatever their ages. The main treatment regimens were sofosbuvir/ledipasvir (37.8%), sofosbuvir/daclatasvir (31.8%), sofosbuvir/simeprevir (16.9%), sofosbuvir/ribavirin (7.8%); ribavirin was given to 24% of patients. The overall sustained virological response (SVR) rate was 91.0 % (95% CI: 89.292.5%) with no difference according to age. Logistic regression of the independent predictors of SVR were albumin, hepatocellular carcinoma and treatment regimen, but not age. The rate of severe adverse events (66 in 59/1062 [5.6%] patients) tended to be greater in patients older than 64 years of age (21/261,8.1%), but the only independent predictors of SAE by logistic regression were cirrhosis and baseline hemoglobin. Patient-reported overall tolerance was excellent in all age groups, and patient-reported fatigue decreased during and after treatment, independent of age. Conclusions The high efficacy and tolerance of interferon-free regimens is confirmed in elderly patients in real-life conditions.

Summary Background and aims According to clinical trials, the treatment of patients with chronic hepatitis C (CHC) with second-generation direct acting antiviral agents (DAAs) is highly efficient and well tolerated. The goal of this study was to investigate the effectiveness and safety of various combinations of these drugs during their first 2 years of use in the real-world practice of French general hospitals. Methods Data from patients treated with all-oral DAAs in 24 French non-academic hospital centers from March 1, 2014 to January 1, 2016, were prospectively recorded. The sustained virological response 12–24 weeks after treatment (SVR 12-24) was estimated and severe adverse events (SAE) were evaluated and their predictive factors were determined using logistic regression. Results Data from 1123 patients were analyzed. The population was 69% genotype (G) 1, 13% G3, 11.5% G4, 5% G2, 49% with cirrhosis and 55% treatment-experienced. The treatment regimens were sofosbuvir/ledipasvir (38%), sofosbuvir/daclatasvir (32%), sofosbuvir/simeprevir (17%), ombitasvir + paritaprevir + ritonavir (5%) (with dasabuvir 3.5%), and sofosbuvir/ribavirin (8%). Ribavirin was given to 24% of patients. The SVR 12-24 was 91.0% (95% CI: 89.2–92.5%). Sofosbuvir-ribavirin was less effective than other regimens. The independent predictors of SVR 12-24 by logistic regression were body weight, albumin, previous hepatocellular carcinoma and treatment regimen (sofosbuvir/ribavirin vs. others). Sixty-four severe adverse events (SAE) were observed in 59 [5.6%] patients, and were independently predicted by cirrhosis and baseline hemoglobin. Serum creatinine increased during treatment (mean 8.5%, [P Conclusions Second generation DAAs combinations are as effective and well tolerated in a « real-world » population as in clinical trials. Further studies are needed on renal tolerance.

International audience; Background: Data on infectious endocarditis (IE) in patients with liver cirrhosis (LC) are sparse. We aimed to describe the characteristics and predictors of mortality from IE in patients with LC.Patients and methods: Overall, 101 patients with LC and 101 controls with IE matched for sex, age, date of IE, and diabetes were retrospectively selected in 23 liver units between 2000 and 2013.Results: Mean age was 60.8±10.5 and 60.6±11.5 years in LC and controls, respectively. Causes of cirrhosis (Child-Pugh A/B/C: 10.4%/41.7%/47.9%, MELD score: 17±7.8) were excess alcohol intake (79.6%), viral hepatitis (17.3%), and metabolic syndrome (14.3%). Previous history of cardiopathy was found in 24.8% of LC (prosthetic valve 8.9%) and 37.6% of controls (P=0.07). The most frequent bacteria involved were gram-positive cocci. LC had significantly fewer aminoglycosides (P=0.0007), rifamycin (P=0.03), and valve surgery (P=0.02) than controls. The proportion of patients who died following cardiac surgery was similar between the two groups (9.7% for LC vs. 8.7% for controls, P=1). In-hospital mortality for Child-Pugh C patients was significantly higher than controls (61.4 vs. 23%, P

IF 7.286; International audience; BACKGROUND:The outcome of cholangiopathy developing in intensive care unit (ICU) is not known in patients surviving their ICU stay.AIM:To perform a survey in liver units, in order to clarify the course of cholangiopathy after surviving ICU stay.METHODS:The files of the liver units affiliated to the French network for vascular liver disease were screened for cases of ICU cholangiopathy developing in patients with normal liver function tests on ICU admission, and no prior history of liver disease.RESULTS:Between 2005 and 2015, 16 cases were retrieved. Extensive burns were the cause for admission to ICU in 11 patients. Serum alkaline phosphatase levels increased from day 11 (2-46) to a peak of 15 (4-32) × ULN on day 81 (12-511). Magnetic resonance cholangiography showed irregularities or frank stenosis of the intrahepatic ducts, and proximal extrahepatic ducts contrasting with a normal aspect of the distal common bile duct. Follow-up duration was 20.6 (4.7-71.8) months. Three patients were lost to follow-up; 2 patients died from liver failure and no patient was transplanted. One patient had worsening strictures of the intrahepatic bile ducts with jaundice. Nine patients had persistent but minor strictures of the intrahepatic bile ducts on MR cholangiography, and persistent cholestasis without jaundice. One patient had normal liver function tests.CONCLUSIONS:In patients surviving their ICU stay, ICU cholangiopathy is not uniformly fatal in the short term or clinically symptomatic in the medium term. Preservation of the distal common bile duct appears to be a finding differentiating ICU cholangiopathy from other diffuse cholangiopathies.

Hepatitis E virus (VHE) is a RNA, non-enveloped, enterically transmitted virus. VHE is present all around the world, with different distribution of its genotypes. VHE of genotypes 1 and 2 predominate in Asia, Africa and in Mexico, responsible for outbreaks transmitted through contaminated water, with an increased mortality in pregnant women. Genotype 3 VHE are globally distributed, with an animal reservoir (swine mainly) endemic in high-income countries. They are transmitted by the ingestion of raw or poorly cooked meat, and possibly by other routes (water, molluscs?) not yet firmly established. Rare post-transfusion hepatitis E cases have been reported. The prevalence of viremic blood donations is around 5 to 10,000 in Europe and in France. Screening tests and/or alternative strategies for viral elimination could be implemented soon.

To describe the characteristics of a cohort of patients with microscopic colitis (MC; lymphocytic (LC) or collagenous (CC) colitis) and to compare them with patients with functional bowel disorder with diarrhea (FBD-D).Between September 2010 and June 2012, patients fulfilling the following inclusion criteria were prospectively included in 26 centers in France: (i) having at least three bowel movements daily with change in stool consistency; (ii) duration of abnormal bowel habit4 weeks; and (iii) normal or near-normal colonoscopy. Each patient underwent a colonoscopy and colonic biopsies. We compared the demographic, clinical, biological, and etiological characteristic of patients with MC (CC and LC) with those of control patients with FBD-D.A total of 433 patients were included: 129 with MC (87 LC and 42 CC), 23 with another organic disease, and 278 with FDB-D, including patients with diarrhea and abdominal pain who met the criteria of Rome III (irritable bowel syndrome with diarrhea) and patients with functional diarrhea without abdominal pain. Logistic regression analysis identified the following independent predictors of MC: age50 years (odds ratio (OR)=3.1, 95% confidence interval (CI)=1.6-5.9), presence of nocturnal stools (OR=2, 95% CI=1.1-3.9), weight loss (OR=2.5, 95% CI=1.3-4.7), duration of diarrhea12 months (OR=2.0, 95% CI=1.1-3.5), recent introduction of new drugs (OR=3.7, 95% CI=2.1-6.6; P0.0001), and the presence of a known autoimmune disorder (OR=5.5, 95% CI=2.5-12).Age50 years, the presence of nocturnal stools, weight loss, the introduction of a new drug, and the presence of a known autoimmune disease increase the probability of MC and thus the indication for colonoscopy with biopsies.

Resume Objectifs Evaluer la prevalence des symptomes extradigestifs (SED) (asthme, douleur pharyngee, enrouement chronique, sensation d’etouffement nocturne, toux chronique, toux nocturne, douleurs thoraciques pseudo-angineuses) suspects dus a un reflux gastro-œsophagien (RGO) dans une population consultant en medecine generale. Comparer la demarche diagnostique et therapeutique adoptee initialement puis lors du suivi a celle recommandee par la conference de consensus franco-belge sur le RGO de l’adulte (1999). Methodes Cette enquete a ete realisee aupres de 578 medecins generalistes (MG). Les differents SED ont ete systematiquement recherches chez tous les patients (≥ 18 ans) consultant sur trois jours. Seuls les patients consideres a priori comme ayant un ou des SED en rapport avec un RGO ont ete inclus dans l’etude. A chaque consultation (C1 a l’inclusion, C2 a 1 mois et C3 a 4 mois), la demarche diagnostique et therapeutique a ete analysee, notee et le degre de certitude du MG sur la responsabilite du RGO dans ces SED quantifie sur une echelle visuelle analogique (EVA). Les criteres ayant conduit les MG a considerer la responsabilite du RGO comme certaine ou douteuse ont ete etudies. Resultats Sur un total de 33 487 consultants, 14 % decrivaient des SED (toux : 6,7 % ; symptome ORL : 7,7 % ; douleur thoracique : 2,3 %). Parmi les patients avec SED, 22 % (1063) ont ete inclus dans l’etude pour suspicion de RGO alors que 45 % (481) ne decrivaient ni antecedents ni symptome digestif typique de RGO. L’attitude diagnostique n’etait pas differente selon que le patient avait des symptomes typiques de RGO associes aux SED (A+) ou non (A−) : 83,7 % des patients (A+) versus 86,5 % (A−) ont recu d’emblee un traitement anti-reflux, 4,9 % (A+) versus 7,9 % (A−) ont eu des examens complementaires et 5,2 % (A+) versus 4,4 % (A−) un avis specialise. Le traitement anti-reflux initial comprenait a 87 % un inhibiteur de la pompe a protons (IPP) [demi-dose : 47 % ; pleine dose : 50 % ; double dose : 2,5 %], un prokinetique dans 3,2 % des cas et un autre medicament dans 13 % des cas. Au terme des quatre mois de suivi, la responsabilite du RGO etait consideree comme certaine chez 74,7 % des patients inclus (794/1063). L’opinion du MG reposait sur la reponse au traitement anti-reflux a 92 %, sur l’endoscopie a 6,7 %, sur la pHmetrie a 0,3 % et sur un avis specialise a 6 % des cas. Conclusions Il existait une difference importante entre les recommandations de la conference franco-belge de consensus sur le RGO de l’adulte et les pratiques observees en medecine generale. La demarche diagnostique et therapeutique etait empirique avec recours aux examens complementaires dans moins de 10 % des cas. Le degre de certitude sur la responsabilite du RGO reposait essentiellement sur la reponse au traitement par les IPP.

Background & Aims The aim of this study was to determine the influence of coffee and other caffeinated drinks on liver fibrosis of severely obese European patients. Methods A specific questionnaire exploring various types of coffee (regular filtrated coffee and espresso), caffeinated drinks, and chocolate was filled in by 195 severely obese patients. All patients had liver biopsies that were analyzed according to the NASH Clinical Research Network Scoring System. Univariate and multivariate analyses of significant fibrosis were performed. Results Caffeine came mainly from coffee-containing beverages (77.5%). Regular coffee and espresso were consumed in 30.8% and 50.2% of the patients, respectively. Regular coffee, espresso, and total caffeine consumption was similar between patients with and without NASH. While consumption of espresso, caffeinated soft drinks, and chocolate was similar among patients, with respect to the level of fibrosis, regular coffee consumption was lower in patients with significant fibrosis (F ⩾2). According to logistic regression analysis, consumption of regular coffee was an independent protective factor for fibrosis (OR: 0.752 [0.578–0.980], p =0.035) in a model including level of AST (OR: 1.04 [1.004–1.076], p =0.029), presence of NASH (OR: 2.41 [1.007–5.782], p =0.048), presence of the metabolic syndrome (NS), and level of HOMA-IR (NS). Espresso, but not regular coffee consumption was higher in patients with lower HDL cholesterol level, higher triglyceride level, and the metabolic syndrome. Conclusions Consumption of regular coffee but not espresso is an independent protective factor for liver fibrosis in severely obese European patients.

International audience; Background & aims: Hepatitis E virus (HEV) genotypes 3 and 4 cause sporadic cases of infection in developed countries. Being elderly and having an underlying liver disease are the main risk factors for death in this population. Chronic infection has been described in immunocompromised patients. Ribavirin is now the antiviral treatment of choice in solid-organ-transplant recipients with chronic HEV infection. We hypothesized that early short-term treatment of acute HEV infection may be useful for patients with risk factors or undergoing chemotherapy.Methods: Between July 2010 and January 2014, 21 patients diagnosed with acute HEV infection were treated with ribavirin, at 600-800 mg/day for up to 3 months. All serum samples were positive for HEV RNA.Results: Nine patients were treated for severe hepatitis. Six patients were aged >70 years. Four patients were receiving an immunosuppressive therapy for an autoimmune disease and two patients were undergoing chemotherapy for a malignancy. Two patients received a fixed-dose regimen. For all other patients, ribavirin was stopped when HEV became undetectable in the serum. The median duration of ribavirin treatment was 26 days. Two patients developed severe anaemia. Two patients with encephalopathy died. One patient relapsed transiently. All patients were cleared of HEV and regained normalized liver-enzyme levels. Immunosuppressive treatment and chemotherapy could be resumed.Conclusions: Treatment of acute HEV infection using ribavirin seems safe and effective. Short-term treatment tailored to viraemia may be the best regimen for this indication.

Summary Background and objective Mortality of upper gastrointestinal bleeding seems declining. Whether practice guidelines for the management of peptic ulcer bleeding are followed is unknown. We aimed to update epidemiology of peptic ulcer bleeding and to assess the adherence to guidelines in the French community. Methods Between March, 2005 and February, 2006, a prospective multicenter study was conducted including all patients with communautary upper gastrointestinal bleeding. Data from patients with peptic ulcer bleeding were extracted and analyzed. Results Out of 3203 analyzable patients included, 1140 (35.6%) had a peptic ulcer bleeding and 965 of them a duodenal and/or gastric ulcer. Seven hundred and thirty-five were male (64.5%) and mean age was 66.4 years (±18.8). Overall, 699 patients (61.3%) were taking medication inducing upper gastrointestinal bleeding. Two-hundred and sixty-eight (23.5%) patients had endoscopic therapy, 190 (70.9%) of whom had epinephrine injection alone. Among the 349 patients with high risk stigmata on endoscopy (Forrest IA, IB, IIA), 209 (59.9%) underwent endoscopic therapy. One thousand one hundred and seven patients (97.1%) were given proton-pump inhibitors. One hundred and thirty-four patients (11.8%) experienced haemorrhagic recurrence. Forty-eight patients (4.2%) underwent surgery and 61 (5.4%) died. Conclusions Consistently with previous studies, mortality of upper gastrointestinal bleeding seems declining. Further progress lies above all in prevention but also probably in better adherence to therapeutic guidelines and management of comorbidities.

BACKGROUND Results of treatments for chronic hepatitis C virus are only estimated and disclosed from pivotal trials. AIM To report the 'true life' results of pegylated interferon and ribavirin in treatment-naive patients. METHODS A prospective, multicenter observatory in 22 general hospitals. RESULTS Five-hundred and one patients were included, with 309 men (62%), aged 46 ± 11 years, weighting 70 ± 13 kg, infected with the following hepatitis C virus genotypes: 1 (50%), 2 (12%), 3 (28%), 4 (7.5%), 5 (0.6%). Liver biopsy, available in 436 patients showed stage F3 fibrosis in 24% and F4 in 13%. Two-hundred and seven patients had a comorbid condition. Treatment consisted of interferon alpha 2b in 340 patients and interferon alpha 2a in 161 patients. Dose reductions were necessary in 145 patients (29%). Treatment was prematurely interrupted in 145 patients (29%) owing to lack of efficacy (n =72) or side-effects (n =73). Sustained virological response (SVR) rates were 50% for all patients, and 37.1, 70.5, and 71% for patients with genotype 1, 2 and 3, respectively. At multivariate analysis, age, genotype, and fibrosis severity were the only independent factors of SVR. CONCLUSION In true life, patients are older and more severe, and SVR is about 10% lower than in pivotal trials.

Resume Dans les pays industrialises, l’infection par le virus de l’hepatite E (VHE) a tres longtemps ete consideree comme une pathologie virale rare et importee. Aujourd’hui, elle est a l’origine de cas sporadiques majoritairement autochtones. Les sources de contamination et les modes de transmission restent a ce jour mal identifies. Toutefois, des cas d’hepatite E par consommation de viande animale et de rares cas par transmission parenterale ont recemment ete decrits. De plus, le taux de mortalite rapporte dans les pays industrialises pourrait etre superieur a celui observe dans les pays en voie de developpement. Ce constat pourrait etre la consequence d’une population atteinte plus âgee et plus frequemment porteuse d’une comorbidite hepatique (mortalite de 70 % dans ce groupe de malades). En revanche, alors que la mortalite chez les femmes enceintes est de 20 % dans les pays en voie de developpement, aucun deces pendant la grossesse n’a ete rapporte en cas d’hepatite aigue E autochtone dans les pays industrialises. Enfin, le virus de l’hepatite E pourrait etre a l’origine d’une hepatite chronique chez les malades immunodeprimes principalement chez les malades greffes avec une evolution possible vers la cirrhose.

Summary Background Few data are available on the incidence, risk factors and contamination pathways involved in acute indigenous hepatitis E in developed countries. Aims To draw up an overall picture of hepatitis E cases, to confirm whether or not the majority of the cases were indigenous and to attempt to identify the risk factors and contamination pathways involved in hepatitis E. Methods This study was performed in the framework of a national network (ANGH) including 96 participating centres. The 19 centres with at least one case of acute HEV reported a total number of 53 cases. Results A decreasing South-to-North geographic gradient was observed. A nonspecific clinical profile was observed in many cases. Acute hepatitis E was of indigenous origin in 90% of the patients. The most relevant and/or frequent possible risk factors among the 47 indigenous metropolitan cases were water consumption from a personal water supply, uncooked shellfish consumption and the recent acquisition of a pet pig. Conclusions This national survey confirmed that acute indigenous hepatitis E is an emerging disease in developed countries such as France, and suggests that various risk factors are responsible for acute indigenous hepatitis E contamination in non-endemic countries.

Summary Background Epidemiological data concerning hepatitis B are scarce in France. Aim To describe epidemiological, clinical, virological and histological features of HBsAg-positive patients followed at non-academic hospitals in France. Methods Clinical, biological, virological and histological data of all HBsAg-positive consecutive patients observed from April 1, 2001 to May 31, 2002 in participating centres were recorded prospectively. Multivariate analyses of factors associated with significant fibrosis and cirrhosis were performed. Results Nearly 1166 HBsAg-positive patients were seen in the 58 centres: 671 males and 495 females from metropolitan France (32%) and from outside metropolitan France (68%); mean age 41 ± 15 years. Twenty-nine percent of patients were probable HBsAg inactive carriers, while 50% had chronic hepatitis; 43% of these were HBeAg-positive and 57% HBeAg-negative. Liver biopsy had been performed in 558 (51%) patients; 205 (17.6%) patients had cirrhosis. By multivariate analysis, factors associated with significant fibrosis were: age >40 years (P

International audience; no abstract

Coffee consumption is associated with decreased levels of liver enzyme activities, gamma-GT and aminotransferases (especially when alcohol consumption or increased body mass index are present), a decreased risk of cirrhosis, compensated or not, and of death from cirrhosis (especially from alcoholic cirrhosis), a reduction in fibrosis in various chronic liver diseases and of fibrosis speed of progression in hepatitis C, and with a decrease in the prevalence and incidence of hepatocellular carcinoma. In experimental studies, in animals or in vitro, coffee and some of its components (caffeine, diterpenes, and particularly polyphenols) have shown benefits in term of insulin resistance, lipid metabolism, endothelial function, antioxidant effects (some mediated by Nrf2), apoptosis, glucuronidation, and hepatic fibrogenesis. Therapeutic trials are now awaited.

In two transversal studies (totaling around 400 patients), coffee consumption was associated with a significant or borderline-significant reduction in the fibrosis stage. In a third study (HALT-C, around 1000 patients), dealing only with patients having initially severe fibrosis and not cured by a previous antiviral treatment, the prevalence of cirrhosis was lower in coffee drinkers. Histologic inflammation was reduced in one study, but not in the two other studies, with increasing coffee consumption. Hepatitis C virus load was slightly higher, and aspartate transaminase slightly lower, in coffee drinkers. In patients retreated with peginterferon and ribavirin, virologic responses were higher, and tolerance better, in coffee drinkers. Finally, during a 3.5 year follow-up, HALT-C patients drinking coffee had a reduced risk of disease progression. Coffee consumption could be associated with a more benign presentation and spontaneous and posttherapeutic outcomes in patients with chronic hepatitis C. That coffee itself (or its components) or coffee consumption as a surrogate marker of genetic predisposition(s) is responsible for these putative beneficial effects is unknown.

Summary Objectives To evaluate in naive patients with chronic hepatitis C 1- the efficacy and safety of one month interferon alpha (IFN-α) induction regimen; 2- the potential virological benefit of a secondary adjunction of ribavirin among HCV RNA negative patients after 20 weeks of IFN therapy, with or without an initial 4-week IFN induction. Material and methods 151 naive HCV-RNA positive patients presenting with biopsy- proven chronic hepatitis C and elevated ALT were randomised in a 2: 1 ratio in two arms: IFN-α 3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-α 6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. Results Efficacy of IFN-δ induction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47% vs 12%, P = 0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-α alone: 18/28 (64%) vs 10/26 (39%); P = 0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P = 0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P = 0.99). Conclusion A 4 week IFN-α induction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-α for 6 months in HCV-RNA negative patients after 6 months of IFN-α significantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.

Purpose Randomized studies on tamoxifen treatment of hepatocellular carcinoma (HCC) produced conflicting results. The aim of this study was to assess the efficacy of tamoxifen administration in improving overall survival of patients with advanced HCC. Patients and Methods A total of 420 patients with HCC who were not suitable for surgery or local treatment were randomly assigned between April 1995 and May 2000: 210 in the control group and 210 in the tamoxifen group (20 mg/d orally). Patients with WHO performance status greater than 2, belonging to Child-Pugh class C, or with serum creatinine greater than 130 μmol/L were not eligible. Results Tolerance was good and the main reported adverse effects were thrombophlebitis (three patients), nausea (two patients), and hot flushes (three patients). Outcome did not differ between the two treatment arms: estimated median survival was 4.8 and 4.0 months in the tamoxifen and in the control groups, respectively (P = .25). Univariate analysis showed significant association of survival with age, Okuda stage, WHO performance status, Child-Pugh class, intrahepatic tumor stage, alpha-fetoprotein serum concentration, and presence of extrahepatic spread, portal vein thrombosis, hepatomegaly, or hepatalgia. In a Cox proportional hazards model we found a significant beneficial effect of tamoxifen on survival in patients belonging to Okuda I or II stages. Conclusion In this large study, tamoxifen did not improve the survival of patients with advanced HCC, but there is a suggestion that patients without major hepatic insufficiency seem to have some survival benefit. New trials involving this specific population are warranted.

Summary Background : On-demand treatment may be an alternative in the long-term treatment of non-severe gastro-oesophageal reflux disease in patients with frequent symptomatic relapses. Aim : To compare the efficacy of on-demand treatment with rabeprazole 10 mg versus continuous treatment in the long-term treatment of patients with frequent symptomatic relapses of mild to moderate gastro-oesophageal reflux disease. Methods : This randomized, open-label study enrolled patients diagnosed with non-erosive reflux disease or oesophagitis grade 1 or 2 (Savary–Miller classification) reporting frequent symptomatic relapses (requiring ≥2 courses of antisecretory therapy during the previous year), whose intensity is rated at least moderate (>2 on a 5-point Likert scale). After a 4-week selection phase with rabeprazole 10 mg once daily, patients reporting symptom relief (Likert score ≤2) were randomized to receive either rabeprazole 10 mg continuous treatment or on-demand treatment for 6 months. The main evaluation criterion was the rate of symptom relief (scored on the Likert scale) after 6 months. Results : One hundred and seventy-six patients were enrolled in the 4-week selection phase (men, 53%; mean age, 49 years; non-erosive reflux disease, 36.4%; gastro-oesophageal reflux disease 1, 53.4%; gastro-oesophageal reflux disease 2, 10.2%). Rabeprazole relieved symptoms in 88.6% of patients. Of this group, 152 were randomized to the comparative phase to receive rabeprazole 10 mg continuous treatment (once daily) or on-demand treatment (continuous treatment, n = 81; on-demand treatment, n = 71). At month 6 (end point), the symptom relief rate was slightly higher for patients in the continuous treatment group compared with those in the on-demand treatment group: 86.4% versus 74.6%, respectively. This difference was not statistically significant (P = 0.065). For the overall quality of life score, there was no difference between the continuous treatment and on-demand treatment groups (86.25 and 84.94). Mean daily consumption of rabeprazole was significantly lower in the on-demand treatment group versus the continuous treatment group (0.31 tablets versus 0.96 tablets; P

Resume Objectif Evaluer l’efficacite diagnostique, le cout, les measures correctives possibles des indications de la coproculture standard pour les diarrhees nosocomiales de l’adulte. Methodes Etude retrospective, sur une periode de 10 mois, des 660 coprocultures standards, dont 256 faites apres le 3e jour d’hospitalisation, realisees chez 528 malades au centre hospitalier de Pau. Resultats Le taux de positivite de la coproculture standard etait de 26/336 malades (7,7 %), et de 37/404 examens (9 %) dans les 3 premiers jours d’hospitalisation, contre 2/192 malades (1%) et 3/256 examens (1%) apres le 3e jour d’hospitalisation (p Conclusion La restriction de la coproculture standard au-dela du 3e jour d’hospitalisation aux malades âges de plus de 64 ans avec comorbidite, aux immunodeprimes et a un contexte epidemique permettrait d’economiser environ 4 300 par mois dans un hopital general de taille moyenne. Aucune restriction systematique ne devrait etre appliquee pour la recherche de C. difficile.

No study on bioclinical criteria predicting a biliary origin for acute pancreatitis has included endosonography as a reference examination. Re-examination of bioclinical parameters deserves consideration in the era where other causes are known (e.g. hereditary, autoimmune).To determine the performance of bioclinical markers in predicting a biliary origin of acute pancreatitis where the diagnosis of biliary lithiasis was established or ruled out using endosonography. Only patients with a first acute episode of pancreatitis were included.213 patients (male: 55%; median age: 56 years) were prospectively included in 14 centres. Causes of acute pancreatitis were: biliary (62%), alcoholic (25%), other (13%). Delay between symptom-onset and admission was48 h in 80%. Endosonography was the sole method establishing the diagnosis of biliary pancreatitis in 15% of patients. At univariate analysis, age, female sex, declared alcohol consumption, elevated aspartate and alanine transaminases on admission, gammaglutamyl transferase, alkaline phosphatase, total bilirubin, lipase, mean corpuscular volume were predictive of a biliary origin. Only age (p0.0001), sex (p0.0008) and alanine transaminase (p0.0004) remained significant at multivariate analysis. At age 50, the respective sensitivity and specificity were 73 and 65%. With an elevated alanine transaminase at 2 times the upper limit of normal range, the respective sensitivity and specificity were 74 and 84%. The probability of a biliary origin of acute pancreatitis could be estimated by the following formula: = 1/1 + exp(4.6967 - 0.0656 x age + 1.1208 x sex - 0.6909 x alanine transaminase).When endosonography is performed to confirm or exclude a biliary origin of acute pancreatitis, age, sex and alanine transaminase at admission are the only factors predictive of a biliary cause.

Congenital dyserythropoietic anemias (CDAs) constitute a rare group of inherited red-blood-cell disorders associated with dysplastic changes in late erythroid precursors. CDA type I (CDAI [MIM 224120], gene symbol CDAN1) is characterized by erythroid pathological features such as internuclear chromatin bridges, spongy heterochromatin, and invagination of the nuclear membrane, carrying cytoplasmic organelles into the nucleus. A cluster of 45 highly inbred Israeli Bedouin with CDAI enabled the mapping of the CDAN1 disease gene to a 2-Mb interval, now refined to 1.2 Mb, containing 15 candidate genes on human chromosome 15q15 (Tamary et al. 1998). After the characterization and exclusion of 13 of these genes, we identified the CDAN1 gene through 12 different mutations in 9 families with CDAI. This 28-exon gene, which is transcribed ubiquitously into 4738 nt mRNA, was reconstructed on the basis of gene prediction and homology searches. It encodes codanin-1, a putative o-glycosylated protein of 1,226 amino acids, with no obvious transmembrane domains. Codanin-1 has a 150-residue amino-terminal domain with sequence similarity to collagens and two shorter segments that show weak similarities to the microtubule-associated proteins, MAP1B (neuraxin) and synapsin. These findings, and the cellular phenotype, suggest that codanin-1 may be involved in nuclear envelope integrity, conceivably related to microtubule attachments. The specific mechanisms by which codanin-1 underlies normal erythropoiesis remain to be elucidated.

Hepatitis E virus (VHE) is a RNA, non-enveloped, enterically transmitted virus. VHE is present all around the world, with different distribution of its genotypes. VHE of genotypes 1 and 2 predominate in Asia, Africa and in Mexico, responsible for outbreaks transmitted through contaminated water, with an increased mortality in pregnant women. Genotype 3 VHE are globally distributed, with an animal reservoir (swine mainly) endemic in high-income countries. They are transmitted by the ingestion of raw or poorly cooked meat, and possibly by other routes (water, molluscs?) not yet firmly established. Rare post-transfusion hepatitis E cases have been reported. The prevalence of viremic blood donations is around 5 to 10,000 in Europe and in France. Screening tests and/or alternative strategies for viral elimination could be implemented soon.