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A partir de notre experience d’une consultation de cotherapie pour les couples, nous tentons de conceptualiser le dispositif que nous proposons. Nous commencons par decrire quels sont les « piliers cliniques » qui fondent notre pratique. Ensuite, nous partageons comment notre relation constitue le levier therapeutique essentiel de notre dispositif, grâce a trois elements : le dialogue relationnel, notre liberte a circuler sur le cycle de l’ambiance, autant entre alterite et egalite qu’entre position « intra » et « meta » et enfin, troisieme element indispensable, le plaisir de travailler ensemble.

International audience; Background The increased risk of upper gastrointestinal bleeding (UGIB) related to direct oral anticoagulants (DOACs) as compared to vitamin K antagonists (VKA) remains debated. Aims To describe the epidemiology and outcomes of UGIB in patients treated with oral anticoagulants. Methods A prospective, multicentre study in French general hospitals enrolled all consecutive patients with UGIB during one year. Patients treated with oral anticoagulants were retrieved from the cohort. Main outcomes were mortality and rebleeding during the first 6 weeks and need for non-endoscopic treatment (surgery or interventional radiology). Results Among the 2498 patients included, 475 (19%) had an oral anticoagulant, mostly with VKA (267 patients [56.2%]). Baseline characteristics were similar between the groups except for renal failure and cirrhosis that were more prevalent in the VKA group. Gastroscopy was normal in 73 patients (15.3%); peptic lesions were the main cause of UGIB (n = 233, 49%). Endoscopic treatment was performed in 128 patients (26.9%), leading to bleeding resolution in 74% (n = 95). Mortality rate at 6 weeks was 12.4% (59 patients), and was higher in the VKA group compared to DOACs (16.1% vs 7.8%, P < 0.01). By multivariate analysis, only the Charlson index >= 5 and UGIB occurrring in in-patients were independently associated with mortality. Rebleeding (56 patients [11.8%]) and need for non-endoscopic treatment (18 patients [3.8%]) were not associated with the type of anticoagulant. Conclusion DOACs do not alter outcomes of UGIB as compared to VKA. Comorbidities and associated treatment are the most important factors worsening the prognosis of UGIB.

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.

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.

There is debate over the effects of long-term oral fluoroquinolone therapy in patients with advanced cirrhosis. We performed a randomized controlled trial to evaluate the effects of long-term treatment with the fluoroquinolone norfloxacin on survival of patients with cirrhosis.We performed a double-blind trial of 291 patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy. The study was performed at 18 clinical sites in France from April 2010 through November 2014. Patients were randomly assigned to groups given 400 mg norfloxacin (n = 144) or placebo (n = 147) once daily for 6 months. Patients were evaluated monthly for the first 6 months and at 9 months and 12 months thereafter. The primary outcome was 6-month mortality, estimated by the Kaplan-Meier method, censoring spontaneous bacterial peritonitis, liver transplantation, or loss during follow-up.The Kaplan-Meier estimate for 6-month mortality was 14.8% for patients receiving norfloxacin and 19.7% for patients receiving placebo (P = .21). In competing risk analysis that took liver transplantation into account, the cumulative incidence of death at 6 months was significantly lower in the norfloxacin group than in the placebo group (subdistribution hazard ratio, 0.59; 95% confidence interval, 0.35-0.99). The subdistribution hazard ratio for death at 6 months with norfloxacin vs placebo was 0.35 (95% confidence interval, 0.13-0.93) in patients with ascites fluid protein concentrations15 g/L and 1.39 (95% confidence interval, 0.42-4.57) in patients with ascites fluid protein concentrations ≥15 g/L. Norfloxacin significantly decreased the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria.In a randomized controlled trial of patients with advanced cirrhosis without recent fluoroquinolone therapy, norfloxacin did not reduce 6-month mortality, estimated by the Kaplan-Meier method. Norfloxacin, however, appears to increase survival of patients with low ascites fluid protein concentrations. ClinicalTrials.gov ID: NCT01037959.

Introduction The use of human albumin for the management of cirrhosis has increased. Recommendations have been published for therapeutic paracentesis (TP), spontaneous bacterial peritonitis (SBP), and type 1 hepatorenal syndrome (HRS). The goal of this survey was to assess the prescription practices of French hepatogastroenterologists. Methods All hepatogastroenterologists were contacted. The questionnaire evaluated (1) the use of albumin in validated indications and (2) the prescription of albumin for nonvalidated clinical situations. Results Responses were analyzed from 451 (50.1%) practitioners. The mean age was 40 years (range, 24 to 67 y). Physicians practiced in a university hospital (47.7%) or a general hospital (45.8%). There were 56.7% senior practitioners. Overall 99.6% of the practitioners compensated for TP. Albumin was used by 87.8% of the physicians, with a fixed dose being used by 84.6%. For SBP, 94% of the physicians used albumin concomitantly with antibiotics. The recommended protocol was followed by 56.2% of the practitioners: more often by senior university hospital practitioners than by senior general hospital practitioners (P=0.015). About 66.5% used albumin infusion for the diagnosis of HRS: used more often by senior university hospital practitioners (P=0.0006). Albumin was used concomitantly with vasopressor treatment by 84%; the dose and the duration varied considerably. About 23.5% used albumin for severe bacterial infection, 47.9% for severe hyponatremia, 43.9% for severe hypoalbuminemia, and 65.9% for hydrothorax. Conclusions In this large French survey, albumin is only prescribed in accordance with recommendations for TP. The schedule for SBP is followed by only 56% of the practitioners. The use of albumin for HRS is not adapted to recommendations, which are not well known, suggesting that they should be more diffused.

International audience; BACKGROUND & AIMS:Few people know of autoimmune pancreatitis (AIP), a rare disorder associated with inflammatory bowel diseases (IBD). We aimed to describe phenotype and outcomes of IBD and AIP when associated.METHODS:We performed a retrospective study of cases of AIP in IBD identified from the multicenter Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif in Belgium and France from July 2012 through July 2015. Patients were diagnosed with AIP based on the International Consensus Diagnostic Criteria for AIP. A definitive AIP diagnosis was based on histological analysis of pancreatic resection specimens or samples collected by fine-needle aspiration during endoscopic ultrasound. Patients with probable type 1 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, level of serum immunoglobulin G4, and involvement of other organs. Patients with probable type 2 AIP were identified based on imaging findings, clinical and/or radiologic responses to steroids, and association with IBD. The primary objective was to collect information on the characteristics of AIP in patients with IBD. We also compared features of patients with IBD with and without AIP in a case-control analysis, using multivariate analysis.RESULTS:We analyzed data from 91 individuals with AIP and IBD (47 women) seen at 23 centers (58 had ulcerative colitis [UC] and 33 Crohn's disease [CD]). Eighty-nine patients had type 2 AIP, and 2 patients had type 1 AIP. The mean age at diagnosis of AIP was 35 ± 12 years, and for IBD it was 32 ± 12 years. AIP preceded IBD in 19 patients (21%). Over a mean follow-up period of 5.7 ± 4.9 years, 31 patients (34%) relapsed, 11 patients (12%) developed diabetes, and 17 patients (19%) developed exocrine pancreatic insufficiency. In patients with UC, factors independently associated with AIP included proctitis (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.3; P = .007) and colectomy (OR, 7.1; 95% CI, 2.5-20; P = .0003). In patients with CD, AIP was significantly associated with fewer perianal lesions (OR, 0.16; 95% CI, 0.03-0.77; P = .023), non-stricturing non-penetrating CD (OR, 6.7; 95% CI, 1.25-33.3; P = .0029), and higher rate of colectomy (OR, 27.8; 95% CI, 3.6-217; P = .0029).CONCLUSIONS:In a multicenter retrospective analysis of patients with AIP and IBD, followed for an average of 5.7 ± 4.9 years, we found most to have type 2 AIP. Two-thirds of patients have UC, often with proctitis. One-third of patients have CD, often with inflammatory features. Patients with IBD and AIP have higher rates of colectomy than patients with just IBD.

Summary Background Guidelines recommend antibiotic prophylaxis (AP) in well-selected groups of cirrhotic patients, but the impact of these recommendations has not been assessed in France. Aim To evaluate AP prescription tendencies for gastrointestinal bleeding, and primary and secondary prophylaxis of spontaneous bacterial peritonitis (SBP). Methods Practitioners (n = 1,159) working in general hospitals (GH) or in university hospitals (UH) received a self-administered questionnaire. Results Three hundred and eighty-nine (33.6%; GH 35% and UH 30.4%) practitioners responded. AP was prescribed by 97.7%, 72.3% and 94.8% of practitioners, without significant differences between UH and GH, respectively, for gastrointestinal bleeding (quinolones 48.2%, third-generation cephalosporins 27.7% and amoxicillin-clavulanic acid 22.2%), primary (quinolones 97.2%) and secondary prophylaxis of SBP (quinolones 99%). For gastrointestinal bleeding, ofloxacin (47.6%) and norfloxacin (37.4%) were the main quinolones prescribed, and ceftriaxone (77%) was the main third-generation cephalosporin prescribed. The principal reasons for prescribing AP were a decrease in bacterial infection (88.9% for gastrointestinal bleeding, 91.3% for primary and 94.3% for secondary prophylaxis of SBP), a recommendation by a consensus conference (83%, 38% and 74.4% respectively) and an improvement in survival (72.8%, 41.3% and 57.7% respectively). Only 31.7% of practitioners (39.6% for UH vs. 28.6% for GH; P = 0.038) believed that AP may reduce the risk of bleeding recurrence. Reported side effects (28%) of AP mainly concerned the risk of quinolone resistance (62% of cases). Conclusion Antibiotic prophylaxis is well-recognized by French practitioners, but its routine use depends on the expertise of practitioners. Quinolones remain the main antibiotic class prescribed irrespective of the type of prophylaxis.

Background & Aims Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associe aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. Methods We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. Results Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03). Conclusions In an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn's disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer.

International audience; BACKGROUND AND AIMS: Bleeding from gastric varices is more severe than that from esophageal varices, but its management remains debated. We aimed to determine how French hepatogastroenterologists manage cirrhotic patients with gastric varices.METHODS: Hepatogastroenterologists (n=1163) working in general or university hospitals received a self-administered questionnaire.RESULTS: Overall, 155 hepatogastroenterologists (13.3%) from 112 centers (33.3%; 39/40 university hospitals, 73/296 general hospitals) answered. Primary prophylaxis was used by 98.1% of hepatogastroenterologists as follows: β-blockers 96.1% (93.8 vs. 97.0%; university vs. general hospitals respectively; P=0.57), glue obliteration 16.9% (17.2 vs. 16.3%; P=0.88), and transjugular intrahepatic portosystemic shunt (TIPS) 8.0% (12.7 vs. 4.6%; P=0.12). To manage bleeding, university hospitals had greater local access to glue obliteration (95.4 vs. 68.2%; PCONCLUSION: The management of gastric varices in France is heterogeneous across centers. University hospitals have better access to techniques such as glue obliteration and TIPS. As bleeding from gastric varices has a poor outcome, guidelines should be established to standardize clinical practices and design further studies.

International audience; OBJECTIVES: We aimed to assess the performance of a new strip (Periscreen) for the rapid diagnosis of spontaneous bacterial peritonitis (SBP). METHODS: Ascitic fluid (AF) of cirrhotic patients hospitalized between March 2014 and August 2015 was independently tested by two readers using the new strip, which has four colorimetric graduations (negative, trace, small, and large). SBP was diagnosed on neutrophils in ascites>250/mm(3). Ascites not related to portal hypertension were excluded. RESULTS: Overall, 649 patients from 21 French centers were included and 1,402 AF (803 AF samples from 315 outpatients and 599 samples from 334 inpatients) were assessed. Eighty-four AF samples (17 AF in 9 outpatients and 67 AF in 31 inpatients) were diagnosed as SBP. The prevalence of SBP was 6% (2.1% in outpatients vs. 11.2% in inpatients; P

International audience; BACKGROUND AND AIMS: Tenofovir disoproxil fumarate (TDF) demonstrated potent and sustainable antiviral efficacy and a good safety profile in patients with chronic hepatitis B (CHB) in controlled clinical trials. Real-world data are important to confirm effectiveness and safety data in patient populations encountered in routine clinical practice. METHODS: This non-interventional, prospective, 36-month study included treatment-naive and treatment-experienced patients with CHB initiating their first TDF regimen (monotherapy or combination therapy) in routine clinical practice in France. Clinical, virologic, biochemical, compliance, and safety data were collected. RESULTS: Data from 440 consecutive patients from 58 centers were analyzed. The majority of the cohort was male (71 %), hepatitis B "e" antigen-negative (HBeAg-) (74 %), and treatment-experienced (56 %); 11 % were aged \textgreater/=65 years; and comorbidities were reported in 39 %. After 12 months, 92 % of the overall cohort achieved virologic response (HBV DNA \textless69 IU/mL) which was maintained to 36 months (96 %); virologic response was achieved by \textgreater90 % of patients irrespective of HBeAg status, age, or prior treatment history. At 36 months, 77 % of patients had normal alanine aminotransferase levels. Fourteen patients lost hepatis B surface (HBs) antigen, and seven seroconverted to anti-HBs. TDF was well tolerated over the 36-month study, including in 14 women who became pregnant during the study. Median estimated glomerular filtration rate did not change markedly from baseline irrespective of prior treatment history. CONCLUSIONS: TDF demonstrated potent virologic and biochemical responses across a broad range of patients reflective of routine clinical practice. The safety profile was consistent with results from pivotal trials

International audience; no abstract

Presence of clots in the stomach makes emergency endoscopy difficult in patients with upper gastrointestinal bleeding. We investigated whether the association of erythromycin infusion to gastric lavage could improve stomach cleansing before endoscopy.One hundred patients admitted for upper gastrointestinal bleeding were randomly assigned to receive either gastric lavage plus intravenous erythromycin (250 mg) or gastric lavage plus placebo before endoscopy in a double-blind study. The primary end point was the efficacy of intravenous erythromycin to improve stomach cleansing before endoscopy, assessed by both subjective and objective criteria.Characteristics of patients at admission were similar in both groups. Sixty-six patients had portal hypertension. The gastric mucosa was entirely visualized by the endoscopist in 65% of patients in the erythromycin group, versus 44% in the placebo group (p0.05). The quality of examination of the upper gastrointestinal tract, assessed by using a 10-cm visual analog scale, was better in the erythromycin group (4.2+/-2 vs. 3.3+/-2.2, p0.05). Clots were found in the stomach in 30% of patients in the erythromycin group, versus 52% in the placebo group (p0.05). However, ability to identify the source of bleeding, mean duration of endoscopy, and need for a second-look endoscopy, did not differ between the two groups. Similar results were observed in the subgroup of cirrhotic patients. Erythromycin was well tolerated by all patients.Intravenous erythromycin before endoscopy improves stomach cleansing and quality of endoscopic examination in patients with upper gastrointestinal bleeding, but the clinical benefit is limited.

Summary Aim The guidelines of the American Association for the Study of Liver Diseases recommend performing exploratory paracentesis on each patient with cirrhosis and chronic ascites. The aim of the study was to evaluate the prevalence of spontaneous bacterial peritonitis and culture-negative neutrocytic ascites in a large population of consecutive asymptomatic cirrhotic ascitic ambulatory patients. Methods Patients with cirrhosis and tense ascites hospitalized from January to September 2000 in 5 hepatogastroenterology units prospectively underwent an exploratory paracentesis with cytobacteriological, biochemical and bedside inoculation into aerobic and anaerobic blood culture bottles. Patients studied were not receiving antibiotics except for norfloxacin and had no obvious sign of infection such as fever or hypothermia, chills, unusual abdominal tenderness, de novo or worsening hepatic encephalopathy, recent gastrointestinal bleeding, acute renal failure or marked arterial hypotension. Clinical and biological findings and ascitic fluid cytological and bacteriological results were evaluated at each exploratory paracentesis. The results are given in mean ± standards deviations with range. Results Sixty-seven cirrhotic patients (48M/19F, mean age 59 ± 9 years) had 270 therapeutic paracenteses, preceded by an exploratory aspiration. Fifty-nine patients (88%) had alcoholic cirrhosis. Twenty-five patients (37.3%) received norfloxacin. At first paracentesis 41 (61.2%) and 26 (38.8%) patients were class B and C respectively according to the Child-Pugh classification; the mean Child-Pugh score was 9 ± 1.5. None had suspicion of infection. The mean number of paracenteses was 5 ± 4.3 per patient; 59.6% of the paracenteses (161) were compensated with human albumin. Ascitic protein concentration was 17.5 ± 8.6 g/l, ascitic fluid cell count and number of neutrophils were 127 ± 155/mm 3 and 5.9 ± 14/mm 3 (0-60), respectively. No patient had spontaneous bacterial peritonitis nor culture-negative neutrocytic ascites; 10 cases of monomicrobial bacterascites were observed, all with commensal germs. Conclusions In the absence of obvious signs of infection, the prevalence of spontaneous bacterial peritonitis and culture-negative neutrocytic ascites in asymptomatic cirrhotic outpatients with ascites is near 0%. Moreover, for 100 large volume paracenteses, not performing exploratory paracentesis corresponds to a savings of 5,500 euros, without risk for these patients.

The prevalence and risks factors of bacteriuria in cirrhotics have not been assessed by case-control study, and there are conflicting data concerning the role of liver failure and of ascites. The aims of this study were: i) to evaluate the prevalence of bacteriuria in cirrhotics, ii) to search for associated factors, iii) to evaluate the role of bladder post-void residual volume, and iv) to test the sensitivity of isolated bacteria to norfloxacin.The prevalence and risk factors of bacteriuria on admission were determined by a multicenter prospective case-control study.Two hundred and forty-four cirrhotic patients and 240 controls were studied. Bacteriuria was present in 38 patients (15.6%; IC 5%: 11%-20%) and 18 controls (7.5%; IC 5%: 4.2%-11%; p0.001). By univariate analysis, female sex and ongoing diuretic treatment were associated with bacteriuria (p0.0001 and p0.04, respectively). Pugh's grade, ascites and bladder residual volume were not associated with bacteriuria. By multivariate analysis, female sex (p0.0001) and Child-Pugh score (p0.03) were predictors of bacteriuria. Sensitivity of bacteria to norfloxacin was observed in 94.7%; sterile urine cultures were noted in 95.2% of patients treated with this antibiotic.Bacteriuria is twice as frequent in cirrhotic patients as in matched controls, and there is a trend to association with female sex and liver insufficiency.

Background: Although bacterial infections are frequent in patients with liver cirrhosis, only isolated cases of bacterial meningitis have been reported. Methods: We have reviewed a series of 16 cases of bacterial meningitis in patients with cirrhosis, diagnosed in a single hospital over a 30-year period. Results: Thirteen patients had alcoholic cirrhosis. On presentation, all patients had fever and most of them had an abnormal mental status (coma in 11 cases), but neck stiffness was not present or was delayed for more than 24 h in seven (43.7%) patients. The cerebrospinal fluid white cell count was always elevated, higher than 1000/μl in ten cases. The cerebrospinal fluid culture was positive in 14 (87.5%) patients. Gram-negative bacilli (mainly E. coli ) and L. monocytogenes were the most frequent pathogens, accounting for nine cases. In contrast, S. pneumoniae and N. meningitidis were found in only four cases. Concurrent bacteremia was present in 12 (75%) cases. Ten patients (62.5%) died. Death was meningitis-related in seven patients and due to decompensated liver cirrhosis after clinical recovery from meningitis in the three other patients. Child-Pugh class C was associated with a higher mortality rate (80%, versus 33% for Child-Pugh class A–B), although the difference did not reach statistical significance. Conclusions: Bacterial meningitis should be suspected in every patient with cirrhosis presenting with a febrile coma. If lumbar puncture must be delayed, or if no causative agent can be identified on cerebrospinal Gram stain despite elevated cerebrospinal fluid white cell count, empirical antimicrobial therapy should be started straightaway with ampicillin plus a third-generation cephalosporin in sufficient doses.

We report here a case of acute pancreatitis revealing Behcet's disease in an 18-year-old woman. Pancreatitis was due to ischemia secondary to severe abnormalities of the celiac trunk arteries with pseudo-aneurysms. The outcome was favourable after the administration of corticosteroids and cyclophosphamide. The patient did not experience relapse of pancreatitis 2 years after diagnosis.

In cirrhotic patients with gastrointestinal hemorrhage, bacterial infections are frequent and play a significant role in mortality. We have previously found that patients with a Child-Pugh's class C or a rebleeding are a subgroup of cirrhotic patients with a high risk of infection. The aims of the study were (1) to validate these indicators and (2) to assess the effectiveness of a systemic antibiotic treatment in preventing bacterial infections in bleeding cirrhotics with a high risk of infection. One hundred and nineteen bleeding cirrhotic patients were divided into 3 groups. Patients with a Child-Pugh's class A-B and no rebleeding (i.e., with a low risk of infection) constituted group 1 (n = 55). Patients with a high risk of infection were randomly allocated to serve as controls (group 2, n = 34) or to receive the ciprofloxacin and a combination of amoxicillin and clavulanic acid for 3 days after hemorrhage (group 3, n = 30). This antibiotic prophylaxis was administered first intravenously and then orally when the bleeding was controlled. The study period was defined as 10 days after hemorrhage. Incidence of bacterial infections was significantly higher in patients from group 2 than in patients from group 1 (52.9% vs. 18.2%; P < .001). Moreover, infections were more severe in group 2: a sepsis syndrome or a septic shock developed in 66.7% of infected patients from this group, but in only 20% of infected patients from group 1. Incidence of bacterial infections was much lower in patients from group 3 than in those from group 2 (13.3% vs. 52.9%; P < .001). Eight patients from group 2 (23.5%) and 4 patients from group 3 (13.3%) died during the first four weeks (P-not significant). Septic shock was the cause of death in 3 patients from group 2 and in only 1 patient from group 3. The cost of antibiotic therapy, including antibiotic prophylaxis in group 3, was $208 +/- $63 per patient in group 2 and $167 +/- $42 per patient in group 3 (P < .05). We conclude that (1) patients with a Child-Pugh's class C and/or a rebleeding are a subgroup of cirrhotic patients with a high risk of infection after gastrointestinal hemorrhage and that (2) in these patients, a prophylactic treatment with systemic antibiotics is very effective in preventing bacterial infections.

AIM: To compare the incidence of spontaneous bacterial peritonitis in cirrhotic outpatients and inpatients undergoing therapeutic paracentesis METHODS: From January 1 to May 31, 2004, 1041 patients from 70 different hospitals underwent 2123 therapeutic abdominal paracentesis (AP) performed as a outpatient procedure in 355 and as inpatient procedure in 686 cases respectively. The following parameters were compared prospectively between outpatients and inpatients: spontaneous bacterial peritonitis (SBP) prevalence, age, gender, cause of cirrhosis, symptoms, score and grade according to Child-Pugh classification, cirrhosis complications, antibiotics treatment, serum creatinine, platelet count and ascitic protein concentration. RESULTS: SBP was observed in 91 patients. In the whole population the SBP prevalence was 8.7% (95%CI: 7.2-10.6) it was 11.7% (95%CI: 9.5-14.3) in inpatients and 3.1% (95%CI: 1.7-5.5) in outpatients (P < 0.00001). SBP prevalence was 8.3% (95%CI: 4.3-15.6) in symptomatic outpatients vs 1.2% (95%CI: 0.4-3.4) in asymptomatic outpatients (P < 0.002). Patients undergoing outpatient AP were significantly different from those undergoing inpatient AP; they were older (61.1 ± 11.1 years vs 59.4 ± 11.7 years; P = 0.028), cause of cirrhosis was less often alcohol (83 .7 vs 88.2%; P < 0.001), Child-Pugh score was lower (8.9 vs 10.1; P < 0.001) and more often B than C (63.7% vs 38%; P < 0.001). In addition, in outpatients the platelet count was higher (161 ± 93 Giga/L vs 143 ± 89 Giga/L; P = 0.003), serum total bilirubin concentration was lower (38.2 ± 60.7 μmol/L vs 96.3 ± 143.3 μmol/L; P < 0.0001), and ascitic protein concentration higher (17.9 ± 10.7 g/L vs 14.5 ± 10.9 g/L; P < 0.001) than in inpatients. CONCLUSION: In asymptomatic cirrhotic outpatients, the incidence of spontaneous bacterial peritonitis is low thus exploratory paracentesis could be avoided in these patients without significant risk.

Two sets of prognostic indicators were recently proposed for selection of patients with acute liver failure for emergency liver transplantation. According to the London criteria, patients with non-paracetamol-induced acute liver failure should be referred for liver transplantation when the prothrombin time is >100 s or when any three of the following prognostic indicators are present: age 40 yr; non-A, non-B hepatitis, halothane hepatitis or idiosyncratic drug reaction; duration of jaundice before onset of encephalopathy >7 days; prothrombin time >50 s; serum bilirubin >300 μmol/l. According to the Clichy criteria, in acute viral hepatitis, liver transplantation should be decided in patients with coma or confusion, and Factor V 30 yr). To assess the accuracy of these criteria, 81 non-transplanted patients with non-paracetamol-induced acute liver failure were retrospectively studied. The mortality rate was 0.81. The predictive accuracies, respectively on admission and 48 h before death, were 0.80 and 0.79 for the London criteria, and 0.60 and 0.73 for the Clichy criteria. The positive and negative predictive values, 48 h before death, were 0.89 and 0.47 for the London criteria, and 0.89 and 0.36 for the Clichy criteria, respectively. In the 49 patients with acute viral liver failure, the results of the Clichy criteria were similar. In a subgroup of 24 patients who had not received either fresh frozen plasma or sedative-hypnotic drug, the positive predictive values were equal to 1 for the two sets of prognostic indicators, but the predictive accuracies only slightly increased. Due to low negative predictive values (

International audience; OBJECTIVES: Although there may exist a nosocomial risk of hepatitis C virus (HCV) infection in patients with type 1 or type 2 diabetes, this risk has not been fully investigated thus far and its magnitude is unknown. The aim of this multicenter cross-sectional study was to evaluate the prevalence of, and risk factors for, hepatitis C infection in consecutive hospitalized patients with diabetes and to assess the nosocomial risk and magnitude of HCV infection in these patients. PATIENTS AND METHODS: Consecutive hospitalized patients with diabetes seen in 11 French hepatogastroenterology and diabetology departments were studied. The prevalence of anti-HCV antibodies was compared with that observed in healthy blood donors and individuals seen during routine medical checkup. Diabetic patients with anti-HCV antibodies were compared with patients without anti-HCV antibodies for assessment of risk factors. RESULTS: In total 1561 patients were studied. Independent risk factors for HCV infection were assessed through multivariate analysis. Thirty-three patients (2.11%) had anti-HCV antibodies and 21 (63.70%) had HCV identified risk factors. The prevalence of HCV infection was higher in patients with diabetes than in blood donors (0.08%) or healthy controls (0.20%) (P2) of previous admissions since the onset of diabetes (OR=2.52, P=0.039). CONCLUSION: A nosocomial source of HCV infection in hospitalized diabetic patients is suggested by the increased risk of HCV infection associated with the number of hospitalizations. This may account for at least 36% of cases of HCV infection.

P0796 NEW DIRECT ACTING ANTIVIRALS FOR HEPATITIS C TREATMENT: FIRST RESULTS IN A REAL-LIFE SETTING IN FRANCE A. Pariente, A.-J. Remy, J.-P. Arpurt, I. Rosa-Hezode, C. Renou, R. Arotcarena, G. Macaigne, H. Lison, F. Bourhis, X. Causse, A. Pauwels, S. de Montigny-Lenhardt, V. Jouannaud, H. Labadie, E. Maringe, J.-H. Salloum, E. Gagea, H. Hagege, B. Lesgourgues, on behalf of Association Nationale des Gastroenterologues des Hopitaux generaux (ANGH). Service d’Hepatogastroenterologie, Centre Hospitalier, Pau, Service d’Hepatogastroenterologie, Centre Hospitalier, Perpignan, Service d’Hepatogastroenterologie, Centre Hospitalier, Avignon, Service d’Hepatogastroenterologie, Centre Hospitalier Intercommunal, Creteil, Service d’Hepatogastroenterologie, Centre Hospitalier, Hyeres, Service d’Hepatogastroenterologie, Centre Hospitalier, Lagny-Marne la Vallee, Service d’Hepatogastroenterologie, Centre Hospitalier, Creil, Service d’Hepatogastroenterologie, Centre Hospitalier, Chambery, Service d’Hepatogastroenterologie, Centre Hospitalier Regional, Orleans la Source, Service d’Hepatogastroenterologie, Centre Hospitalier, Gonesse, Service d’Hepatogastroenterologie, Centre Hospitalier, Aubagne, Service d’Hepatogastroenterologie, Centre Hospitalier, Montfermeil, Service d’Hepatogastroenterologie, Centre Hospitalier Delafontaine, Saint-Denis, Service d’Hepatogastroenterologie, Centre Hospitalier, Beaune, Service d’Hepatogastroenterologie, Centre Hospitalier, Meaux, Service d’Hepatogastroenterologie, Centre Hospitalier, Cholet, France E-mail: alex.pariente@free.fr

The guidelines of the American Association for the Study of Liver Diseases recommend performing exploratory paracentesis on each patient with cirrhosis and chronic ascites. The aim of the study was to evaluate the prevalence of spontaneous bacterial peritonitis and culture-negative neutrocytic ascites in a large population of consecutive asymptomatic cirrhotic ascitic ambulatory patients.Patients with cirrhosis and tense ascites hospitalized from January to September 2000 in 5 hepatogastroenterology units prospectively underwent an exploratory paracentesis with cytobacteriological, biochemical and bedside inoculation into aerobic and anaerobic blood culture bottles. Patients studied were not receiving antibiotics except for norfloxacin and had no obvious sign of infection such as fever or hypothermia, chills, unusual abdominal tenderness, de novo or worsening hepatic encephalopathy, recent gastrointestinal bleeding, acute renal failure or marked arterial hypotension. Clinical and biological findings and ascitic fluid cytological and bacteriological results were evaluated at each exploratory paracentesis. The results are given in mean +/- standards deviations with range.Sixty-seven cirrhotic patients (48M/19F, mean age 59 +/- 9 years) had 270 therapeutic paracenteses, preceded by an exploratory aspiration. Fifty-nine patients (88%) had alcoholic cirrhosis. Twenty-five patients (37.3%) received norfloxacin. At first paracentesis 41 (61.2%) and 26 (38.8%) patients were class B and C respectively according to the Child-Pugh classification; the mean Child-Pugh score was 9 +/- 1.5. None had suspicion of infection. The mean number of paracenteses was 5 +/- 4.3 per patient; 59.6% of the paracenteses (161) were compensated with human albumin. Ascitic protein concentration was 17.5 +/- 8.6 g/l, ascitic fluid cell count and number of neutrophils were 127 +/- 155/mm3 and 5.9 +/- 14/mm3 (0-60), respectively. No patient had spontaneous bacterial peritonitis nor culture-negative neutrocytic ascites; 10 cases of monomicrobial bacterascites were observed, all with commensal germs.In the absence of obvious signs of infection, the prevalence of spontaneous bacterial peritonitis and culture-negative neutrocytic ascites in asymptomatic cirrhotic outpatients with ascites is near 0%. Moreover, for 100 large volume paracenteses, not performing exploratory paracentesis corresponds to a savings of 5,500 euros, without risk for these patients.

We report here a case of acute pancreatitis revealing Behcet's disease in an 18-year-old woman. Pancreatitis was due to ischemia secondary to severe abnormalities of the celiac trunk arteries with pseudo-aneurysms. The outcome was favourable after the administration of corticosteroids and cyclophosphamide. The patient did not experience relapse of pancreatitis 2 years after diagnosis.

Over the past two decades, new treatment modalities have been introduced for the management of variceal bleeding. The aim of this retrospective study in a single center was to assess whether these treatments have improved the prognosis for cirrhotic patients with variceal bleeding. We reviewed the clinical records of all patients with cirrhosis admitted to our Liver Intensive Care Unit due to variceal bleeding during the years 1980, 1985, 1990, 1995, and 2000. Whereas balloon tamponade was still the first-line treatment in 1980, patients treated in 2000 received a vasoactive agent, an endoscopic treatment, and an antibiotic prophylaxis in, respectively, 90%, 100%, and 94% of cases. The in-hospital mortality rate steadily decreased over the study period: 42.6%, 29.9%, 25%, 16.2%, and 14.5% in 1980, 1985, 1990, 1995, and 2000, respectively (P < .05). Mortality decreased from 9% in 1980 to 0% in 2000 in Child-Turcotte-Pugh class A patients, from 46% to 0% in class B patients, and from 70% to 32% in class C patients. This improved survival was associated with a decrease of rebleeding (from 47% in 1980 to 13% in 2000) and bacterial infection rates (from 38% to 14%). On multivariable analysis, endoscopic therapy and antibiotic prophylaxis were independent predictors of survival. In conclusion, in-hospital mortality of patients with cirrhosis and variceal bleeding decreased threefold over the past two decades, in concurrence with an early and combined use of pharmacological and endoscopic therapies and short-term antibiotic prophylaxis. (HEPATOLOGY 2004;40:652–659.)

Background Chronic viral hepatitis averages 15% to 20% in heart transplant patients. Several studies have shown that ursodiol may improve liver biochemistry in patients with chronic hepatitis. We used a double-blind randomized controlled trial to evaluate the effect of ursodiol in heart transplant patients with chronic viral hepatitis. Methods Thirty heart patients with chronic viral hepatitis B, C, or non-A-G received ursodiol, 800 mg per day (group 1), and 30 received placebo (group 2) for 12 months. Endpoints were improvement in liver biochemical tests and in total Knodell score. Intent-to-treat and per-protocol analyses were performed. Results At entry, both groups were comparable for all of the studied parameters. During the study period, serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase variations were not different between group 1 and group 2 patients. Knodell score improved in 20% of group 1 patients and in 43% of group 2 patients (NS). Adverse events or mortality were not different in the two groups during the study period. Similar results were observed by intent-to-treat and per-protocol analyses. Conclusions A 12-month course of ursodiol therapy had no effect on liver enzymes or liver histology in heart transplant patients with chronic hepatitis.

747 A 96-WEEK RANDOMIZED TRIAL OF SWITCHING TO ENTECAVIR IN CHRONIC HEPATITIS B PATIENTS WITH A COMPLETE VIROLOGIC RESPONSE TO LAMIVUDINE J. Heo, S.H. Ahn, J.Y. Park, H.Y. Woo, H.J. Lee, W.Y. Tak, S.H. Um, K.T. Yoon, S.Y. Park, Y.S. Seo, C.W. Kim, K.H. Han, M. Cho. Internal Medicine, Pusan National University School of Medicine, Pusan, Internal Medicine, Yonsei University College of Medicine, Seoul, Internal Medicine, Yeungnam University College of Medicine, Internal Medicine, Kyungpook National University College of Medicine, Daegu, Internal Medicine, Korea University College of Medicine, Internal Medicine, Catholic University College of Medicine, Seoul, Republic of Korea E-mail: jheo@pusan.ac.kr

(W+24). Sustained virological response (SVR) defined as HBV-DNA 2000 IU/ml was observed in 24 patients 19/24 were non responders (NPV: 79%). A decline in HBsAg titer 10% at week 12 and week 24, respectively. Conclusions: In patients receiving PEG-IFN plus tenofovir, a SVR was observed in 30% and an HBsAg loss in 11%. Baseline HBsAg titer was predictive of: ≤2000 IU/ml HBsAg loss (100%) and SVR (PPV 50%); >2000 IU/ml non-response (NPV 80%). A lack of ≥10% decline in HBsAg level at week 12 or week 24 allows identifying non-responders with a high NPV 80%. An early (week 12) HBsAg level decline is associated with HBsAg loss.

(W+24). Sustained virological response (SVR) defined as HBV-DNA 2000 IU/ml was observed in 24 patients 19/24 were non responders (NPV: 79%). A decline in HBsAg titer 10% at week 12 and week 24, respectively. Conclusions: In patients receiving PEG-IFN plus tenofovir, a SVR was observed in 30% and an HBsAg loss in 11%. Baseline HBsAg titer was predictive of: ≤2000 IU/ml HBsAg loss (100%) and SVR (PPV 50%); >2000 IU/ml non-response (NPV 80%). A lack of ≥10% decline in HBsAg level at week 12 or week 24 allows identifying non-responders with a high NPV 80%. An early (week 12) HBsAg level decline is associated with HBsAg loss.

To show that germander (Teucrium chamaedrys), an herbal medicine used to facilitate weight loss, may be hepatotoxic and to delineate the nature of the injury.Retrospective study.Liver units of several centers in the French Network of Pharmacovigilance.Seven patients who developed hepatitis after germander administration and who had no other cause of liver injury.Clinical examination, liver function tests, various serologic tests, ultrasonography, and histologic study.Hepatitis characterized by jaundice and a marked increase in serum aminotransferase levels occurred 3 to 18 weeks after germander administration. Liver biopsy specimens in three patients showed hepatocyte necrosis. After discontinuing treatment with germander, jaundice disappeared within 8 weeks and recovery was complete in 1.5 to 6 months. In three cases, germander readministration was followed by the prompt recurrence of hepatitis.Germander may be hepatotoxic, which supports the view that herbal medicines are not always as safe as generally assumed.