Jacques Denis

A survey of patterns of practice and perception of NAFLD in a large sample of practicing gastroenterologists in France

BACKGROUND & AIMS Most studies on non-alcoholic fatty liver disease (NAFLD) originate from tertiary care centers with an academic interest. How this emerging entity is accepted and managed by a wider body of gastroenterologists is unknown, despite significant implications for the diagnosis of at-risk subjects and the utilization of healthcare resources. METHODS We conducted a survey among 352 French, board-certified gastroenterologists from a large variety of practices to understand the clinical burden, perceived severity, and management patterns of NAFLD. RESULTS Half of participants saw >30 new cases (equal to HCV) of NAFLD and 40% >5 new cases of NASH-cirrhosis yearly. Only 20% of patients were referred by endocrinologists; conversely, gastroenterologists overwhelmingly referred NAFLD patients for assessment of metabolic co-morbidities. In patients with metabolic risk factors, a majority of physicians considered the diagnosis of NAFLD, even if other liver diseases co-existed. The diagnosis heavily relies on aminotransferases, hence patients with normal ALT are usually not diagnosed. Liver biopsy is performed for fibrosis staging but not for the diagnosis/grading of steatohepatitis, and mainly decided based on non-invasive fibrosis procedures. Pharmacological treatment is used despite a lack of clear evidence of efficacy. Physicians monitor patients themselves, usually twice a year. CONCLUSIONS NAFLD is recognized and accepted as a disease in itself with potentially severe outcomes. Most at-risk patients are currently missed because of non-referral by endocrinologists and no exploration of those with normal aminotransferases. The medical need for the diagnosis and treatment of NAFLD is real in the community of gastroenterologists at large.

Epidemiological and prognostic factors involved in upper gastrointestinal bleeding: results of a French prospective multicenter study.

BACKGROUND AND STUDY AIMS The mortality rate from upper gastrointestinal bleeding (UGIB) remains high, at 5 % - 10 %. The aim of the current study was to describe the epidemiological characteristics, prognostic factors, and actual practice in a cohort of patients with UGIB admitted to French general hospitals. METHODS From March 2005 to February 2006, a prospective multicenter study was conducted at 53 French hospitals. A total of 3298 patients admitted for UGIB were enrolled consecutively. Patient data were collected up to the date of discharge from hospital. RESULTS Data were available for 2130 men and 1073 women (mean age 63 ± 18 years), one-third of whom were taking drugs that would increase the risk of UGIB. The two main causes of bleeding were peptic ulcers (38 %) and esophagogastric varices (EGV) or portal hypertensive gastropathy (24.5 %). Mean Rockall score was 5.0 ± 2.3. Endoscopy was performed on 96 % of patients (within 24 hours in 79 %), and 66 % of those with ulcers and 62.5 % of the EGV patients underwent hemostatic therapy when indicated. Rebleeding occurred in 9.9 % of the patients, and 8.3 % died. Independent predictors of rebleeding were: need for transfusion (odds ratio [OR] 19.1; 95 % confidence interval [95 %CI] 10.1 - 35.9); hemoglobin < 10 g/dL (OR: 1.7; 95 %CI 1.1 - 3.3); Rockall score (OR: 1.4 for each 1 point score increase; 95 %CI 1.0 - 1.9), systolic blood pressure < 100 mmHg (OR: 1.9; 95 %CI 1.4 - 2.5), and signs of recent bleeding (OR: 2.4; 95 %CI 1.7 - 3.5). Independent predictors of mortality were: Rockall score (OR: 2.8; 95 %CI 2.0 - 4.0), co-morbidities (OR: 3.6 for each additional co-morbidity; 95 %CI 2.0 - 6.3), and systolic blood pressure < 100 mmHg (OR: 2.1; 95 %CI 1.8 - 2.8). Rockall score, blood pressure and co-morbidities were taken as continuous variables meaning that the OR was 1.4 for every point increase, it was the same for blood pressure. CONCLUSION UGIB still occurs mainly as a result of peptic ulcers and portal hypertension in France, and causes significant rates of mortality. There is scope for improvement via better prevention (better use of UGIB-facilitating drugs), endoscopic therapy, and management of co-morbidities.

Epidemiology of chronic hepatitis B infection in France: risk factors for significant fibrosis - results of a nationwide survey

Background  Epidemiological data concerning hepatitis B are scarce in France.

A national French survey on the use of growth factors as adjuvant treatment of chronic hepatitis C

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.)

Prevalence and risk factors of bacteriuria in cirrhotic patients: a prospective case-control multicenter study in 244 patients

BACKGROUND/AIMS 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. METHODS The prevalence and risk factors of bacteriuria on admission were determined by a multicenter prospective case-control study. RESULTS 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%; p<0.001). By univariate analysis, female sex and ongoing diuretic treatment were associated with bacteriuria (p<0.0001 and p<0.04, respectively). Pughs grade, ascites and bladder residual volume were not associated with bacteriuria. By multivariate analysis, female sex (p<0.0001) and Child-Pugh score (p<0.03) 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. CONCLUSION 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.

Coeliac disease in chronic hepatitis C: a French multicentre prospective study

Background  A prevalence of 1.2% of coeliac disease (CD) in patients with chronic hepatitis C was recently reported, suggesting a possible epidemiological link between these two diseases. However, other studies have not found this relationship.

Epidemiology and adherence to guidelines on the management of bleeding peptic ulcer: A prospective multicenter observational study in 1140 patients

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.

Treatment of chronic hepatitis C with pegylated interferon and ribavirin in treatment-naive patients in 'true life': a plea in favor of independent postmarketing evaluations.

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

Hépatite chronique C: gestion des effets indésirables du traitement.

Resume Le traitement de l’hepatite chronique C, bien codifie maintenant avec l’association d’un interferon pegyle alpha et de la ribavirine, permet d’obtenir une guerison dans plus de la moitie des cas. Les resultats sont encore meilleurs, et atteignent pres de 70 % de reponse virologique prolongee, lorsque le traitement est optimise. Malgre ces succes therapeutiques, un pourcentage non negligeable de malades est en echec therapeutique, principalement a cause des effets indesirables du traitement qui aboutissent a des reductions de doses ou a une interruption prematuree du traitement. Les principaux effets secondaires en cause sont la fatigue, des douleurs musculaires et articulaires, les troubles de l’humeur et du sommeil, la depression, l’anemie et la leucopenie. Ces divers effets secondaires peuvent modifier considerablement la qualite de vie des malades. Il est donc important de les prendre en charge rapidement apres leur apparition, ou meme de tenter de les anticiper. Il apparait essentiel d’assurer une education therapeutique bien adaptee de facon a ce que le malade puisse mieux comprendre son traitement et y adherer plus facilement afin d’obtenir une plus grande chance de guerison.

Prevention of relapse in patients with chronic non-A, non-B/C hepatitis who respond to alpha-interferon. A controlled multicenter trial of low-dose maintenance therapy

We tested the efficacy of maintenance treatment with alpha-2a interferon, 1 megaunit thrice weekly for 6 months, in preventing relapse of non-A, non-B/C hepatitis in remission after treatment with alpha interferon given thrice weekly according to the following dose schedule: 3 megaunits for 3 months, 2 megaunits for 2 months and 1 megaunit for 1 month. Fifty-three patients with hepatitis C in remission were randomly allocated to a treatment group (n = 26) or a control group (n = 27). A relapse (aminotransferase activity > 1.5 times the upper limit of normal) occurred in 46% of the controls and 35% of the treated patients (NS). Maintenance treatment had no significant influence on histopathologic changes evaluated by three independent observers: in both groups the overall score for histologic lesions improved between the initiation of interferon therapy and the end of the study. We conclude that relapses in patients with non-A, non-B/C hepatitis in remission after treatment with alpha interferon at tapering doses are not prevented by maintenance therapy with low-dose alpha interferon. Journal of Hepatology.