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International audience; Background: Crohn's disease (CD) is a chronic disorder requiring long-term treatment. However, up to 20% of patients interrupt temporarily or permanently anti-TNFα. Primary aim was to identify internal and external factors influencing patient's motivation to pursue anti-TNFα in active CD.Methods: This was a French, multicentre, prospective study enrolling CD patients on anti-TNFα therapy since more than 3 months. Patients completed the Satisfaction of Patients with Crohn's Disease questionnaire (SPACE-Q) and other patient-reported-outcome tools at inclusion visit, and after 6 and 12 months.Results: A total of 274 patients were included: 146 (53.3%) received adalimumab, while 128 (46.7%) infliximab. Most patients (78%) were still treated with anti-TNFα 12 months after enrolment. Patients' perception of necessity (p = 0.01) and concerns (p

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

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.

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.

Background and study aims: The purpose of this study was to describe the real-life conditions of use, efficacy, safety, and acceptability of sodium phosphate (NaP) tablets for colon cleansing in routine medical practice in France. Patients and methods: A total of 996 patients undergoing bowel preparation were enrolled by 108 gastroenterologists in this observational, longitudinal, prospective, multicenter study. The conditions of use of NaP tablets were assessed with a composite endpoint, which included six criteria for patient compliance with the recommended administration scheme and a criterion for the absence of contraindications to NaP use. Results: Adequate use of NaP was reported for 75.1 % of the patients. The main reasons for misuse were a smaller fluid intake than expected with a dose of 4 tablets and noncompliance with age-related contraindications. The quality of cleansing was satisfactory: the Boston Bowel Preparation Scale (BBPS) total score was 7 or higher in 75.4 % of the patients. Gastroscopy associated with colonoscopy in 38.9 % of the patients revealed gastric lesions, which were considered as possibly related to the use of NaP tablets in 10.3 % of them. Vomiting occurred in 9.8 % of the patients, and 0.6 % discontinued bowel preparation after an adverse event. No electrolyte disorders or renal impairment was reported, even if not systematically sought. The acceptability of the NaP tablets was high, particularly among patients who previously had undergone other methods of bowel preparation. Conclusions: Despite being defined according to strict criteria, adequate use of NaP tablets was observed in a high percentage of patients. The quality of colon cleansing and the safety and acceptability of NaP tablets were satisfactory and consistent with data from randomized clinical studies.

BACKGROUND Several studies have suggested the efficacy of baclofen in reducing alcohol consumption, leading to a temporary recommendation for use in France. AIM Our aim was to report our experience in using baclofen in alcohol-dependant patients with or without liver cirrhosis. PATIENTS AND METHODS Consecutive patients from two liver and alcohol units were recruited over a 3-year period and received increasing doses of baclofen associated with social, psychological, and medical care. RESULTS One hundred patients were treated, of whom 65 were cirrhotic. After 1 year, 86 patients were still being followed up. At a mean dosage of 40 mg/day (extremes: 30-210), the median daily alcohol consumption reduced from 80 to 0 g/day (P

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).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.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).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: Aminosalicylates are first-choice treatment for mild-to-moderately active ulcerative colitis (UC); however, multi-dosing regimens are inconvenient. AIM: To compare the efficacy and safety of once- (OD) vs. twice- (BD) daily prolonged-release mesalazine (Pentasa, Ferring, Saint-Prex, Switzerland) for active mild-to-moderate UC in a non-inferiority study. METHODS: Eligible patients (n = 206) were randomised to 8 weeks of mesalazine (4 g/day), either OD with two sachets of 2 g mesalazine granules in the morning (n = 102) or BD with one 2 g sachet in the morning and one in the evening (n = 104). Patients also received 4 weeks of mesalazine enema 1 g/day. Disease activity was assessed at randomisation, weeks 4, 8 and 12 using the UC Disease Activity Index (UC-DAI). Clinical and endoscopic remission (primary endpoint) was assessed after 8 weeks. Patients recorded stool frequency and rectal bleeding in a daily diary. RESULTS: The primary endpoint, non-inferiority in clinical and endoscopic remission with OD vs. BD mesalazine at 8 weeks, was met (intent-to-treat population: 52.1% vs. 41.8%, respectively, 95% confidence interval -3.4, 24.1; P = 0.14). Improvement of UC-DAI score (92% vs. 79%; P = 0.01) and mucosal healing (87.5% vs. 71.1%; P = 0.007) were significantly better, time to remission significantly shorter (26 vs. 28 days; P = 0.04) and safety similar with OD vs. BD dosing. CONCLUSIONS: When combined with mesalazine enema, prolonged-release mesalazine once-daily 4 g is as effective and well tolerated as 2 g twice-daily for inducing remission in patients with mild-to-moderately active ulcerative colitis (Clinicaltrials.gov: NCT00737789).

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 & 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.

BACKGROUND: Non-organ-specific autoantibodies (NOSAs) are frequently found in the sera of patients with Hepatitis C Virus (HCV) infection. However, no conclusive answers have been produced concerning the clinical relevance of these antibodies. AIM: To determine whether a relationship might exist between the presence of NOSA and the severity of liver disease in chronic hepatitis C. METHODS: 186 treatment-naive chronic hepatitis C patients were studied consecutively for autoantibodies. Liver biopsies were analyzed according to the Metavir score. RESULTS: NOSAs were present in 75 patients (40%). Anti-nuclear antibodies were found in 32% of patients (speckled pattern), anti-smooth muscle in 15% without F-actin specificity, anti-mitochondria in 0.5%, and anti-LKM1 in 0.5%, respectively. No liver-cytosol1 or soluble liver antigen antibodies were detected. There was a highly significant correlation between the positivity of NOSA and the degree of inflammation and hepatocellular injury (p = 0.001) and also with the degree of fibrosis (p < 0.0001). The presence of NOSA was associated with higher aspartate aminotransferase, gamma-glutamyl-transpeptidase, gamma-globulin and immunoglobulin G levels. By contrast, no differences were observed regarding age, gender, route of infection, duration of disease, HCV genotypes or viral load. CONCLUSION: NOSAs were associated with the most severe forms of chronic HCV infections.

Background/Aims Portosystemic shunting, whether surgical or transjugular intrahepatic, has been a cornerstone of therapy for Budd–Chiari syndrome. However, the long-term impact of shunt dysfunction remains unknown. We have assessed this long-term impact in patients with surgical shunting. Methods Thirty-nine consecutive patients operated on between 1978 and 2000 were analyzed using time-dependent multivariate Cox model. Results Median follow-up was 110 months. Prosthetic shunts and high preshunt portal venous pressure were predictors of subsequent shunt dysfunction. Among 19 patients with persistently patent shunt, as compared to 20 patients with shunt dysfunction, 1 versus 18 developed refractory ascites; 1 versus 7 had variceal bleeding; 7 versus 2 had encephalopathy; 3 versus 11 (55%) died or underwent liver transplantation; and 0 versus 10 died from end-stage liver disease. Shunt dysfunction was associated with a shorter survival ( p =0.001). Out of 20 patients with shunt dysfunction, seven had successful revision of the shunt. None of these seven patients had refractory ascites after revision or died from end-stage liver disease. Conclusions In patients with Budd–Chiari syndrome treated with portosystemic shunting, shunt dysfunction has a major impact on morbidity and mortality.

Summary Aim of the study The aim of this retrospective multicenter study was to collect data from patients with chronic alcoholic pancreatitis and cystic dystrophy of the duodenal wall in order to better understand the outcome after medical, endoscopic and/or surgical treatment. Patients and methods The data from medical records of 23 patients consecutively seen in ten primary referral centers from January 1990 to July 2004 were studied. Clinical, biological, and endoscopic features as well as imaging findings were recorded. Response to treatment was noted. Results Twenty-three patients (20 men), aged 45 years (range: 30-66), with chronic alcohol intake, cystic dystrophy of the duodenal wall, and previously known (N = 14) or simultaneously diagnosed (N = 9) chronic pancreatitis were included. Symptoms most frequently encountered were abdominal pain (N = 22) and weight loss (N = 16). An abdominal ultrasound was available for 10 patients, abdominal computed tomography for 22, upper endoscopy for 18, and endoscopic ultrasonography for 22. Endoscopic ultrasonography enabled diagnosis of cystic dystrophy of the duodenal wall in 19/22 patients. Six patients were symptom-free after alcohol withdrawal. Seven patients received octreotide 200 to 400 mg per day, 5 of whom subsequently underwent surgery (71%). Fourteen patients out of 23 were operated on (61%), 11 of whom underwent pancreaticoduodenectomy and remained symptom-free for 47 months follow-up. Mean follow-up was 56 months (range: 2-78) for non surgical patients (39%) and 47 months (range: 12-108) for surgical patients (61%). Conclusion Cystic dystrophy of the duodenal wall complicating chronic alcoholic pancreatitis may be the revealing sign of pancreatitis. Endoscopic ultrasongraphy is the most reliable imaging method for diagnosis. Pancreaticoduodenectomy is the most frequently employed definitive treatment.

Chronic granulomatous disease may lead to inflammatory bowel disease with endoscopic and histological aspects similar to that observed in patients with Crohn's disease. Inflammatory symptoms are generally controlled by steroids, but resistant forms may need total colectomy. Therapeutic strategy in steroid-dependent cases is not yet established. We report here the case of a patient with chronic granulomatous enteritis dependent on steroids at a daily dose of 20 mg. Azathioprine made it possible to withdraw steroid therapy without relapse over twenty Months and without infectious complication during the follow up.

Hélène Gilet,1 Benoit Arnould,1 Fatoumata Fofana,1 Pierre Clerson,2 Jean-Frédéric Colombel,10 Olivier D’Hondt,2 Patrick Faure,4 Hervé Hagège,5 Maria Nachury,3 Stéphane Nahon,6 Gilbert Tucat,7 Luc Vandromme,8 Ines Cazala-Telinge,9 Emmanuel Thibout9 1HEOR and Strategic Market Access, Mapi, Lyon, France; 2Orgamétrie, Roubaix, France; 3Hôpital Claude Huriez, Lille, France; 4Clinique Saint-Jean du Languedoc, Toulouse, France; 5Centre Hospitalier Intercommunal, Créteil, France; 6Centre Hospitalier Intercommunal, Le Raincy Montfermeil, France; 7Gastroenterologist, Private Clinical Practice, Paris, France; 8Gastroenterologist, Private Clinical Practice, Reims, France; 9Abbvie France, Rungis, France; 10Icahn School of Medicine at Mount Sinai, New York, NY, USA Background: Severe Crohn’s disease management includes anti-tumor necrosis factor (anti-TNF) drugs that differ from early-stage treatments regarding efficacy, safety, and convenience. This study aimed to finalize and psychometrically validate the Satisfaction for PAtients in Crohn’s diseasE Questionnaire (SPACE-Q©), developed to measure satisfaction with anti-TNF treatment in patients with severe Crohn’s disease. Methods: A total of 279 patients with severe Crohn’s disease receiving anti-TNF therapy completed the SPACE-Q 62-item pilot version at inclusion and 12 and 13 weeks after first anti-TNF injection. The final SPACE-Q scoring was defined using multitrait and regression analyses and clinical relevance considerations. Psychometric validation included clinical validity against Harvey–Bradshaw score, concurrent validity against Treatment Satisfaction Questionnaire for Medication (TSQM), internal consistency reliability, test–retest reliability, and responsiveness against the patient global impression of change (PGIC).Results: Quality of completion was good (55%–67% of patients completed all items). Four items were removed from the questionnaire. Eleven scores were defined within the final 58-item SPACE-Q: disease control; symptoms, anal symptoms, and quality of life transition scales; tolerability; convenience; expectation confirmation toward efficacy, side effects, and convenience; satisfaction with treatment; and motivation. Scores met standards for concurrent validity (correlation between SPACE-Q satisfaction with treatment and TSQM satisfaction scores =0.59), internal consistency reliability (Cronbach’s α=0.67–0.93), test–retest reliability (intraclass correlations =0.62–0.91), and responsiveness (improvement in treatment experience assessed by the SPACE-Q for patients reporting improvement on the PGIC). Significantly different mean scores were observed between groups of patients with different Harvey–Bradshaw disease severity scores.Conclusion: The SPACE-Q is a valid, reliable, and responsive instrument to measure satisfaction with anti-TNF treatment in patients with severe Crohn’s disease and for use in future studies. Keywords: Crohn’s disease, satisfaction, anti-TNF treatment, questionnaire

INTRODUCTION Renal dysfunction has recently been described as a potential complication of tritherapy with telaprevir (TVR) in patients with chronic hepatitis C. This study aimed to identify predictive factors for and consequences of TVR-associated renal dysfunction. PATIENTS AND METHODS A retrospective-prospective study was carried out in 96 patients with chronic hepatitis C, genotype 1, treated with TVR-based tritherapy in 2012-2013, in whom regular serum creatinine measurements were performed during the first 12 weeks of treatment. The patients received standard doses of peginterferon, ribavirin and TVR (2250 mg/day). The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula. RESULTS eGFR decreased significantly from baseline at weeks 4, 8 and 12, the mean maximum decrease being 22.0±23.6 ml/min, with a significant correlation between baseline and minimum eGFR (r=0.58, P

Hepatitis C is frequently associated with immune-mediated diseases, such as cryoglobulinemia. Guillain-Barré syndrome is an acute demyelinating neuropathy of probable immune pathogenesis. We describe two patients with Guillain-Barré syndrome, and associated chronic hepatitis C, the second one previously treated with interferon. The link between both conditions may be hepatitis C being the trigger of this immune polyneuropathy. Guillain-Barré syndrome should be added to the list of conditions associated with hepatitis C.

Resume La mutation du facteur V Leiden, responsable d’une resistance a la proteine C activee, est une affection prothrombotique observee chez environ 20 % des malades ayant un premier episode de thrombose veineuse profonde. Nous rapportons le cas d’une femme de 30 ans, suivie pour des crises douloureuses abdominales recidivantes, hospitalisee pour un infarctus du grele par thrombose mesenterique veineuse et arterielle, ayant necessite une resection etendue du grele. Le bilan a la recherche de facteurs de risque de thrombose mettait en evidence une resistance a la proteine C activee secondaire a une mutation homozygote du facteur V Leiden. Un traitement anticoagulant au long cours etait institue. Des douleurs abdominales inexpliquees doivent faire evoquer une ischemie mesenterique, laquelle peut etre secondaire a une mutation du facteur V Leiden.

Claire Marant1, Benoit Arnould1, Alexia Marrel1, Céderic Spizak1, Jean-Frédéric Colombel2, Patrick Faure3, Hervé Hagege4, Marc Lemann5†, Stéphane Nahon6, Gilbert Tucat7, Luc Vandromme8, Emmanuel Thibout9, Gérard Goldfarb91Mapi Values, Patient-Reported Outcomes, 27 rue de la Villette, Lyon, France; 2Hepatology and Gastroenterology Department, Hôpital Claude Huriez, Lille, France; 3Hepatology and Gastroenterology Department, Clinique Saint-Jean du Languedoc, Gastrologie, Toulouse, France; 4Hepatology and Gastroenterology Department, Centre Hospitalier Intercommunal, Créteil, France; 5Hepatology and Gastroenterology Department, Hôpital Saint Louis, Paris, France; 6Hepatology and Gastroenterology Department, Centre Hospitalier Intercommunal, Le Raincy Montfermeil, France; 7Gastroenterologist, Clinical practice, Paris, France; 8Gastroenterologist, Clinique de Courlancy, Reims, France; 9Abbott France, Rungis, France †Deceased.Purpose: To develop a self-administered questionnaire assessing patients’ satisfaction with treatments in Crohn’s disease for use in clinical research and epidemiological studies.Patients and methods: Semi-directive interviews (16) were conducted with patients with severe Crohn’s disease treated with anti-tumor necrosis factor alpha (anti-TNFα). Transcripts were analyzed and concepts related to satisfaction with treatment were extracted and organized into a model. Items were generated using patients’ words. The resulting test version was tested for relevance and comprehension with 7 patients and revised accordingly; the new version was tested with 5 other patients and revised to provide the pilot version. A clinician advisory board was involved at each milestone of the development.Results: The test questionnaire assessed treatment satisfaction through 67 items, organized into 5 sections: treatment efficacy, side-effects, convenience and constraints, overall impact, and satisfaction. Conceptual content of the questionnaire includes comparison with prior state and with expectations, satisfaction, acceptability, and intentions. The questionnaire was generally well accepted and understood by patients; few modifications were made in the structure and item formulation. After the second round of comprehension tests, the pilot version contained 62 items; the questionnaire was named Satisfaction of PAtients in Crohn’s diseasE (SPACE©).Conclusion: The questionnaire is a unique tool to assess treatment satisfaction in patients with Crohn’s disease. A scoring and validation study is currently being performed to finalize and establish its scoring, as well as its psychometric properties.Keywords: Crohn’s disease, anti-TNF treatment, questionnaire, patient satisfaction, patient-reported outcome

Juxtapapillary diverticula are often associated with biliary lithiasis. The aim of this study was to compare the prevalence of juxtapapillary diverticula in choledocholithiasis and in cholecystolithiasis without common bile duct stones. The results of 520 consecutive retrograde cholangiographies were retrospectively analysed. The prevalence of juxtapapillary diverticula was higher in patients with biliary lithiasis than in patients without: 26.0% vs 10.5% (p less than 0.001). However, juxtapapillary diverticula were more frequently encountered in patients with choledocholithiasis than in those with gallbladder lithiasis or previous cholecystectomy and a stone-free common bile duct: 40.0% vs 10.2% (p less than 0.001). There was no significant difference between the patients with cholecystolithiasis alone and those without biliary lithiasis. Among the patients with previous cholecystectomy or with gallbladder lithiasis, common bile duct stones were more frequently found in patients with juxtapapillary diverticula than in those without: 80.3% vs 40.6% (p less than 0.001). These data suggest that juxtapapillary diverticula are associated only with choledocholithiasis and not with gallbladder lithiasis.

Asymptomatic bacterascites is defined as the presence of bacteria in ascitic fluid without clinical features of peritonitis or increased ascitic fluid polymorphonuclear cells. Asymptomatic bacterascites is a controversial entity, and little information is available regarding its spontaneous evolution. Clinical features, bacteriological data and outcome in 22 cirrhotic patients with asymptomatic bacterascites are reported and are compared with those of a group of 36 cirrhotic patients with spontaneous bacterial peritonitis. Eleven patients had gram-negative bacteria and 11 had one gram-positive bacteria. Only in three patients (13.6%) did peritonitis develop. Twelve patients received no antibiotic therapy, and in none did peritonitis develop. At 1 month, 27% of patients with asymptomatic bacterascites had died. Patients with asymptomatic bacterascites had less-severe liver disease; they more frequently had gram-positive bacteria in ascitic fluid and had a lower 1-mo mortality rate than did patients with spontaneous bacterial peritonitis. We conclude that asymptomatic bacterascites is usually the transient residence of bacteria in ascitic fluid. Peritonitis rarely develops in patients with asymptomatic bacterascites and, in most of them, antibiotic therapy is not required.

We conducted a national retrospective survey on hospital practitioners to evaluate the magnitude of erythropoietin (EPO) or granulocyte colony-stimulating factor (G-CSF) prescriptions in patients treated for chronic hepatitis C. Four hundred seventy-one questionnaires were sent, and 274 practitioners (58.2%) responded. Forty-six percent of practitioners used EPO, and 31% used G-CSF. The total number of HCV-infected patients receiving antiviral therapy per year was estimated at 6,630 patients, of whom 8.8% and 4% received EPO and G-CSF, respectively. EPO-β was the main EPO molecule prescribed at a median dose of 30,000 IU/wk (range: 2,000-80,000). The indications for prescribing EPO varied greatly, including “fragile patients” (34%), “low” Hb level (8-11 g/dL) (19%), “rapid decline” in Hb level (2-5 g/dL during the first month of therapy) (12%), and symptomatic anemic patients (7%). G-CSF was mainly prescribed for a “low” level of neutrophils ranging from 400 to 750 neutrophils/mm3. In multivariate analysis, independent predictors of EPO and G-CSF prescription were age of practitioner less than 45 years (EPO: OR = 1.96, P = 0.03; G-CSF: OR = 2.27, P = 0.004), practice in university hospital (EPO: OR = 5.89, P < 0.0001; G-CSF: OR = 2.39, P = 0.003), and the high number of CHC treated/year (EPO: OR = 6.18, P < 0.0001; G-CSF: OR = 2.58, P = 0.002). Conclusion: Our survey reveals an important rate of EPO and G-CSF prescriptions but with considerable disparity in the schedule of injections, the molecules used, and above all the indications. The suitable role of EPO and G-CSF as complements to HCV therapy urgently needs to be clarified. (HEPATOLOGY 2007;45:377–383.)

The aim of this retrospective multicenter study was to collect data from patients with chronic alcoholic pancreatitis and cystic dystrophy of the duodenal wall in order to better understand the outcome after medical, endoscopic and/or surgical treatment.The data from medical records of 23 patients consecutively seen in ten primary referral centers from January 1990 to July 2004 were studied. Clinical, biological, and endoscopic features as well as imaging findings were recorded. Response to treatment was noted.Twenty-three patients (20 men), aged 45 years (range: 30-66), with chronic alcohol intake, cystic dystrophy of the duodenal wall, and previously known (N=14) or simultaneously diagnosed (N=9) chronic pancreatitis were included. Symptoms most frequently encountered were abdominal pain (N=22) and weight loss (N=16). An abdominal ultrasound was available for 10 patients, abdominal computed tomography for 22, upper endoscopy for 18, and endoscopic ultrasonography for 22. Endoscopic ultrasonography enabled diagnosis of cystic dystrophy of the duodenal wall in 19/22 patients. Six patients were symptom-free after alcohol withdrawal. Seven patients received octreotide 200 to 400 microg per day, 5 of whom subsequently underwent surgery (71%). Fourteen patients out of 23 were operated on (61%), 11 of whom underwent pancreaticoduodenectomy and remained symptom-free for 47 months follow-up. Mean follow-up was 56 months (range: 2-78) for non surgical patients (39%) and 47 months (range: 12-108) for surgical patients (61%).Cystic dystrophy of the duodenal wall complicating chronic alcoholic pancreatitis may be the revealing sign of pancreatitis. Endoscopic ultrasongraphy is the most reliable imaging method for diagnosis. Pancreaticoduodenectomy is the most frequently employed definitive treatment.

Chronic granulomatous disease may lead to inflammatory bowel disease with endoscopic and histological aspects similar to that observed in patients with Crohn's disease. Inflammatory symptoms are generally controlled by steroids, but resistant forms may need total colectomy. Therapeutic strategy in steroid-dependent cases is not yet established. We report here the case of a patient with chronic granulomatous enteritis dependent on steroids at a daily dose of 20 mg. Azathioprine made it possible to withdraw steroid therapy without relapse over twenty Months and without infectious complication during the follow up.

Leiden Factor V mutation, associated with resistance to activated protein C, is a prothrombotic state found in 20% of the patients with a first episode of deep-vein thrombosis. We report the case of a 30-Year-old woman with a history of intermittent abdominal pain who developed small bowel infarction requiring extensive small bowel resection. Biological search for prothrombotic disorder showed resistance to activated protein C due to homozygosity for the factor V Leiden mutation. Long-term anticoagulant therapy was initiated. Unexplained abdominal pain may be due to venous mesenteric ischemia, which can be associated with factor V Leiden mutation.

Background and Aims: The endoplasmic reticulum (ER) is a multifunctional organelle involved in synthesis, processing and folding of proteins, lipid biosynthesis, and regulation of calcium and redox homeostasis. Altered ER-function due to accumulation of misfolded/unfolded proteins, oxidative stress or depletion of ER calcium, lead to a condition called “ER-stress”, particularly important in cells with a high burden of protein synthesis as hepatocytes. Efavirenz, a non-nucleoside analog reverse transcriptase inhibitor, is a cornerstone in the combined therapy of HIV1 infection. Despite being considered generally safe, it has been related to development of adverse events such as hepatic toxicity. Here we report the presence of specific ER-stress in human hepatic cells. Methods: Hep3B cells and primary human hepatocytes were exposed to short-term treatment (24h) with clinically relevant concentrations of Efavirenz. General cell biology methods were employed (RNA interference, RT-PCR, Western blot and fluorescence microscopy). Results: ER-stress markers indicative of several ER-stress pathways were up-regulated concentration-dependently by Efavirenz, including the expression of CHOP and GRP78, at protein and mRNA level, and the phosphorylated form of eIF-2a. Furthermore, we also detected an increase in the transcription of ATF4 and XBP-1, and presence of the spliced form s-XBP-1. Efavirenz also induced morphological changes in ER with enhanced ER-content and dilatation of its cisternae, and led to an increase in the cytosolic calcium level. All these changes were similar to those produced by the standard pharmacological ER-stressor, Thapsigargin. On the contrary, while Thapsigargin induced an increment in the mitochondrial calcium level, Efavirenz provoked a decrease. A differential effect was also observed with transient silencing of CHOP. The stimulating effect of Thapsigargin on the generation of reactive oxygen species and the increment in the ER-content was more pronounced in CHOP-depleted cells, but this exacerbated action was not observed when cells were treated with Efavirenz. Conclusions: Clinical concentrations of Efavirenz induce ER-stress in hepatic cells in a compound-specific manner. Given the lifelong and widespread use of Efavirenz in the multidrug therapy of HIV, this novel mechanism of cellular response to drug-induced stress could help to understand the frequent hepatic toxicities that accompany the treatment of HIV1 infection.

perception of QoC compared with patients’ perception showed that patients scored the care dimension “competence” and “costs” higher and “continuity of care” lower than physicians (Table 1). Conclusions: QoC in this Italian IBD cohort is good, and well compares to previously published results in different European Countries. Physicians’ and patients’ perspectives are similar, although physicians overscore continuity of cares and underscore competence and costs compared to patients. The results of this study may contribute to ameliorate standards of practice in order to optimize QoC for IBD in Italy.

Gastrointestinal Bleeding Due to Mallory-Weiss Syndrome: Part of a French Prospective Study on Upper GI Bleeding Stephane Nahon*, Jean Henrion, Alexandre Pariente, Bruno Bour, Jean-Paul Latrive, Herve Hagege Service de Gastroenterologie, Centre Hospitalier Le RaincyMontfermeil, Montfermeil, France; Service d’Hepatogastroenterologie, Hopital de Jolimont, Haine Saint Paul, France; Service d’Hepatogastroenterologie, Hopital de Pau, Pau, France; Service d’Hepatogastroenterologie, Hopital du Mans, le Mans, France; Service d’Hepatogastroenterologie, Hopital de Compiegne, Compiegne, France; Hopital de Creteil, Creteil, France Aim: Little data is available on the upper gastrointestinal bleeding (UGIB) associated resulting from Mallory-Weiss syndrome (MWS). The aim of this study was to describe the characteristics and identify the prognostic factors of UGIB associated with MWS. Patients and methods: A subgroup of patients with UGIB secondary to MWS was isolated from the data recorded on UGIB at the French ANGH observatory in 2005 to 2006. The epidemiological characteristics and prognostic factors of the patients in the MWS subgroup were compared with those of patients with peptic ulcer bleeding (n 965). Results: The subgroup studied here consisted of 148 men and 56 women (mean age 52.9 21.3 years), accounting for 6.4% of the all the patients recorded at this observatory. Endoscopic treatment, which was performed in 20.6% of cases (corresponding to 34% of active bleeding), consisted in performing a sclerosing injection alone in 28 cases, associated with a clip in 4 cases, or with a ligature in one case and with argon plasma coagulation in 2 cases. Ligation alone was performed in one case and a clip alone in 5 cases. Patients with MWS were younger (52.9 21.4 vs. 66.6 18.7, p 0.0001), more frequently male (72.5% vs. 64.9%, p 0.04), and tended more frequently to have cirrhosis (17.6% vs. 8.9%, p 0 .0001), to have fewer transfusions (32.5% vs. 71.5%, p 0 .0001), a lower rate of recurrent bleeding (3.9% vs. 12.7%, p 0 .0001), surgery (0.5% vs. 5.3%, p 0.002) and a shorter hospital stay (5.85 4 vs. 9 8.6, p 0.0001). No significant differences were observed between the rates of active bleeding (59.8% vs. 64.8%, p 0.2), endoscopic treatment (20.6% vs 25.4%, p 0.2) or mortality (2.9% vs. 5.7%, p 0.1) in the two groups. The 6 deaths were not directly due to the bleeding but to comorbid conditions. Conclusion: UGIB secondary to MWS is less severe than that due to peptic ulcers and the mortality is mainly due to comorbidities.

perception of QoC compared with patients’ perception showed that patients scored the care dimension “competence” and “costs” higher and “continuity of care” lower than physicians (Table 1). Conclusions: QoC in this Italian IBD cohort is good, and well compares to previously published results in different European Countries. Physicians’ and patients’ perspectives are similar, although physicians overscore continuity of cares and underscore competence and costs compared to patients. The results of this study may contribute to ameliorate standards of practice in order to optimize QoC for IBD in Italy.

In this paper, three cases of grand mal seizures are reported as a complication of pefloxacin at usual doses (400 mg twice a day) in patients with cirrhosis. Grand mal seizures occurred from 12 h to 8 days after the onset of pefloxacin treatment. In 1 case, seizures recurred after inadvertent rechallenge with the drug. Elevated pefloxacin serum levels were demonstrated in 2 cases. Brain computed tomography in all 3 cases and cerebrospinal fluid examination showed normal results. No etiology other than pefloxacin overdose was found. After pefloxacin withdrawal, no recurrence of seizures were observed. Therefore, when pefloxacin treatment is indicated for cirrhotic patients, a reduced dosage and/or careful monitoring of pefloxacin serum levels should be recommended.

Introduction La prise en charge du syndrome de l’intestin irritable (SII) represente une part importante de l’activite du gastroenterologue. La place des traitements alternatifs y est mal connue. L’objectif de cette enquete nationale etait d’evaluer pour la premiere fois le recours a ces therapeutiques et le niveau de satisfaction des patients. Patients et Methodes Les patients inclus etaient adultes et consultaient un gastroenterologue pour un SII. Un questionnaire medical precisait la symptomatologie et les traitements medicamenteux ou alternatifs. Un auto-questionnaire patient anonyme portait sur les professionnels de sante consultes, l’information recue et le niveau de satisfaction vis-a-vis des traitements. Parmi les 790 gastroenterologues sollicites, 644 (81,5 %) ont participe a cette enquete menee de mars a septembre 2008. 2 933 paires de questionnaires medecin-patient etaient analysables. Resultats Les patients etaient en majorite des femmes (72 %), etaient âges de 52 ± 16 ans et souffraient d’un SII depuis 10 ± 11 ans. Il s’agissait d’un nouveau patient pour le gastroenterologue dans 37 % des cas. 82 % des patients estimaient avoir recu l’information souhaitee sur leur SII. Parmi les symptomes les plus frequemment observes on notait : douleur : 91 %, ballonnements : 62 %, constipation : 37 %, epigastralgies : 22 %). Sur une echelle visuelle analogique allant de 0 a 10 le niveau de satisfaction generale des patients sur leur prise en charge etait de 5,1 ± 2,5 et 28 % avaient un niveau de satisfaction ≤ 3. Vis-a-vis du traitement medicamenteux traditionnel, le niveau de satisfaction etait de 4,9 ± 2,4 et 31 % des patients avaient un niveau de satisfaction ≤ 3. 20 % des patients avaient eu recours au cours des 12 derniers mois a un ou plusieurs traitements alternatifs (13 % selon les medecins, p Conclusion Au cours du SII, plus de 80 % des patients considerent leur niveau d’information comme satisfaisant. Les gastroenterologues sous-estiment le recours de leurs patients a des traitements alternatifs. Ce recours est lie a l’anciennete du SII, l’alternance diarrhee-constipation, les ballonnements et l’anxiete-depression. Ces diverses therapeutiques alternatives ne donnent pas un niveau de satisfaction superieur aux traitements traditionnels.

Introduction Une enquete realisee en 2000 avait montre que dans les Centres Hospitaliers Generaux (CHG), 50 % des hepato-gastroenterologues (HGE) estimaient consacrer 10 a 30 % de leur temps a l’oncologie digestive. Le developpement des indications de chimiotherapie (CT) semble s’accompagner d’une activite croissante dans ce domaine. La Federation des Specialistes des Maladies de l’Appareil Digestif a realise une nouvelle enquete par questionnaire, comparable, et dont les resultats concernant les CHG sont rapportes ici. Materiels et Methodes D’octobre 2007 a mars 2008, 3 714 questionnaires anonymes ont ete remis (Assises d’Oncologie Digestive) puis adresses par voie postale aux HGE francais. Ils concernaient leur profil, leur type d’exercice, leur participation aux reunions de concertation pluridisciplinaire de cancerologie (RCP), leur pratique de la chimiotherapie, du suivi endoscopique des cancers, leur pratique des soins palliatifs et leur participation a des essais therapeutiques. Resultats Le taux de reponse global a ete de 45 % (1 663). Les repondeurs avaient un exercice predominant en secteur liberal (48 %), hospitalier non universitaire (27 %) et hospitalo-universitaire (15 %). Parmi les 446 repondeurs des CHG, 31 % etaient âges de 35 a 44 ans, 37 % de 45 a 54 ans, 25 % avaient plus de 54 ans. Les femmes representaient 69 % des moins de 35 ans, moins de 15 % des plus de 45 ans. La part estimee attribuee a la cancerologie etait de 10 a 30 % du temps pour 39 % des repondeurs, > 30 % pour 37 % des repondeurs. La participation aux RCP etait de 95 %. Parmi les repondeurs, 300 (67 %) posaient leurs indications de CT dont 144 pour tous leurs malades, et 283 (64 %) pratiquaient eux-memes la CT, dont 161 pour tous leurs patients. Ceux qui ne pratiquaient pas la CT la deleguaient surtout a des oncologues medicaux. La participation declaree aux essais cliniques etait importante (28 %). Pres de la moitie (44 %) des repondeurs des CHG etait titulaire d’une competence ordinale et/ou du DESC de cancerologie et dans ce groupe, la pratique de la CT atteignait 71 %. L’autre moitie prenait en charge des CT pour 58 %, apres un Diplome Universitaire (DU) ou inter-universitaire (DIU) de cancerologie pour la moitie d’entre eux. Parmi les HGE repondeurs sans competence ordinale, ni DESC, ni DU/DIU, 47 % posaient des indications de CT et 44 % prenaient en charge des CT. Discussion Depuis 2000, la place de l’oncologie digestive dans l’activite des HGE de CHG s’est largement accrue : en 2008, un quart seulement des repondeurs y consacrait moins de 10 % de son temps et plus de la moitie pratiquait la CT, avec une participation massive en RCP. Un nombre important d’HGE prescrivait les CT sans reconnaissance officielle de competence, peut-etre grâce a la presence d’un oncologue de soutien dans leur etablissement. Conclusion L’oncologie digestive est devenue une part tres importante du travail des HGE des CHG, qui appliquent le plan cancer et s’impliquent dans la prise en charge multi-disciplinaire des cancers digestifs. Les demarches en cours, en vue de la validation des acquis de l’experience, devraient permettre une regularisation administrative rapide des conditions de prescription des CT dans certains CHG. Remerciements, financements, autres Enquete financee par un don du laboratoire Sanofi-Aventis.