Jean-Baptiste Nousbaum

Epidemiology and course of acute upper gastro-intestinal haemorrhage in four French geographical areas

Objective To compare incidence rates and epidemiological characteristics of acute upper gastrointestinal haemorrhage (AUGIH) in France with those of other European studies. Design Population‐based multi‐centre prospective survey. Setting 29 public hospitals and 96 private specialists in gastroenterology in four administrative areas in France during 1996. Subjects A total of 2133 AUGIH patients 18 years and over were included in the six‐month study. Outcome measures Incidence and mortality. Results The overall incidence in France was 143 cases per 100 000 persons per year, classified as out‐patients (16%), emergency admissions (59%) and in‐patients (25%). The incidence rates increased with age except for in‐patients, and were higher in males. Peptic ulcer (36.6%), varices (13.7%) and erosive disease (12.3%) were the most frequent diagnoses. In 677 patients (31.7%), aspirin, antiinflammatory drugs or corticosteroids were taken on the 7 days before bleeding. The overall mortality (out‐patients excluded) was 14.3% (10.7% for emergency patients and 23% for in‐patients). Mortality was associated with comorbidities (especially malignancies, cirrhosis, asthma or respiratory deficiency), was lower in emergency patients using non‐steroid anti‐inflammatory drugs, and higher in in‐patients using corticosteroids. Conclusions In France, patients with AUGIH are frequently managed as out‐patients. Gastrotoxic drug use is frequently associated with AUGIH and constitutes a strategic opportunity for preventive treatment. Discrepancies between countries are not clearly explained either by demographic factors or by drug use, but this may be related to the emphasis on AUGIH in in‐patients. Eur J Gastroenterol Hepatol 12:175‐181

Diagnostic accuracy of the Multistix 8 SG reagent strip in diagnosis of spontaneous bacterial peritonitis

Recent studies have shown that the diagnosis of spontaneous bacterial peritonitis (SBP) can be rapidly obtained using leukocyte esterase reagent strips. However, published studies were restricted to one or two centers, and the number of patients with SBP was thus limited. The aims of the current prospective multicenter study were: (1) to assess the diagnostic accuracy of the Multistix 8SG urine test for the diagnosis of SBP; and (2) to assess the prevalence of SBP. From January to May 2004, 2 reactive strips were tested independently in inpatients with cirrhosis and in outpatients undergoing paracentesis. Cultures of ascitic fluid were performed at the bedside using aerobic and anaerobic blood culture bottles. Two thousand one hundred twenty‐three paracenteses were performed in 1,041 patients from 70 centers. One hundred seventeen samples, obtained from 91 patients, had ascites polymorphonuclear cell (PMN) counts ≥250/μl (range, 250–34,000), among which 56 were associated with positive ascitic fluid cultures. The prevalence of SBP was 5.5% in the whole population, 9% in inpatients, and 1.3% in outpatients (P < 0.0001). The prevalence of SBP was 0.57% in asymptomatic outpatients versus 2.4% in symptomatic outpatients (P = 0.04). Using a threshold of 2+ for positivity of the reagent strip, sensitivity was 45.3% for the diagnosis of SBP, specificity was 99.2%, positive predictive value was 77.9%, and negative predictive value was 96.9%. Conclusion: This study confirms the low prevalence of SBP in asymptomatic outpatients according to a priori defined criteria, and indicates an absence of diagnostic efficacy for this specific strip test. (HEPATOLOGY 2007;45:1275–1281.)

Anti-inflammatory drugs and variceal bleeding: a case-control study

Background Non-steroidal anti-inflammatory drugs (NSAIDs) can have severe gastrointestinal effects and cause peptic ulcers to bleed. Acute bleeding from oesophageal varices is a major complication of cirrhosis of the liver. Aims To investigate the role, using a case-control study, of NSAIDs in first bleeding episodes associated with oesophageal or cardial varices in cirrhotic patients. Patients/Methods A structured interview was conducted of 125 cirrhotic patients with bleeding mainly related to oesophageal varices and 75 cirrhotic controls with oesophageal varices who had never bled. Results Cirrhotic patients who were admitted for bleeding related to portal hypertension were more likely to have used NSAIDs during the week before the index day (31 of 125 (25%)) than the cirrhotic controls (eight of 75 (11%); odds ratio = 2.8, p = 0.016). Use of aspirin alone or combined with other NSAIDs was also more prevalent in the cases (21 of 125 (17%)) than in the controls (three of 75 (4%); odds ratio = 4.9, p = 0.007). Logistic regression analysis showed that NSAID use (p = 0.022, odds ratio = 2.9, 95% confidence interval = 1.8 to 4.7) and variceal size (p<0.001, odds ratio = 4.0, 95% confidence interval = 1.4 to 11.5) were the only variables independently associated with the risk of bleeding. Conclusions Aspirin, used alone or combined with other NSAIDs, was associated with a first variceal bleeding episode in patients with cirrhosis. Given the life threatening nature of this complication, the possible benefit of this treatment should be weighed against the risk shown here. No firm conclusions could be drawn on non-aspirin NSAIDs used alone.

Phenotype-genotype correlation in haemochromatosis subjects

Abstract Haemochromatosis is a common autosomal recessive genetic disorder of iron metabolism. A candidate gene was recently identifed (HLA-H) and two amino acid substitutions (C282Y and H63D) were characterized. Haemochromatosis probands (n = 478) from Brittany were selected from their iron status markers, primarily serum iron, serum ferritin and transferrin saturation. We investigated the relationships between haemochromatosis phenotype and genotypes at the HLA-H locus and surrounding markers. As already reported, we observed that the C282Y substitution is unambiguously associated with the haemochromatosis phenotype, haemochromatosis patients homozygous for the substitution (Tyr/Tyr) accounting for 81.2% of all haemochromatosis patients. A clear heterogeneity in serum ferritin and transferrin saturation values, and in iron removed by phlebotomy was observed among haemochromatosis patients that is correlated with the presence of two subgroups of individuals homozygous and non-homozygous for the mutant allele C282Y, the latter being characterized by lower phenotypic values. In this subgroup, sequencing did not reveal any other mutation in the HLA-H gene, hence the genotype remained unclear. Thus, an additional non-genetic cause, other mutations or another gene can not be excluded as explanations for the results in these patients.

Factors associated with liver steatosis and fibrosis in chronic hepatitis C patients.

UNLABELLED Liver steatosis is a common finding in patients infected with hepatitis C virus (HCV). Host and viral factors have been associated with steatosis, but their relative contributions have not been clearly addressed. It has been suggested that steatosis plays a role in the progression of liver fibrosis. AIMS To assess: a) factors associated with steatosis in patients infected with hepatitis C virus; b) their impact on liver fibrosis. PATIENTS AND METHODS Three hundred and fourteen untreated patients were included. Lifetime alcohol consumption was estimated. Liver fibrosis, inflammation and necrosis were assessed using the METAVIR score. Body mass index (BMI) was determined. The scoring system for steatosis was as follows: 0, no steatosis; 1, less than 10%; 2, 10% to 30%; 3, 30% to 70%; 4, more than 70% of hepatocytes affected. RESULTS In univariate analysis, steatosis was associated with elevated BMI (P=0.001), excessive alcohol intake (P=0.005), genotype 3 (P<0.001) and moderate to severe histological activity (P=0.01). Multivariate analysis showed that steatosis correlated with two independent factors: genotype 3a (OR=60.7; 95% CI: 7.6-483.4) (P<0.001) and BMI (OR=4.86; 95% CI: 1.8-13.15) (P=0.002). In univariate analysis, severe fibrosis (F2-F3-F4) was associated with older age (P<10(-5)), male gender (P=0.001), disease duration (P<0.006), BMI (P<10(-4)), alcohol intake (P<10(-6)), severity of histological activity (P<10(-5)) and steatosis (P<10(-6)). In multivariate analysis, three independent factors were associated with severe fibrosis: disease duration > 10 years (OR=3.17; 95% CI: 0.65-15.4) (P=0.015), presence of steatosis (OR=3.17; 95% CI: 1-9.99) (P<0.049) and genotype 3a (OR=5.56; 95% CI: 1.4-22.1) (P=0.015). CONCLUSION In patients with chronic hepatitis C, steatosis is significantly associated with genotype 3 infection and high BMI. Steatosis is an independent risk factor associated with severe fibrosis. These results have major implications for the management of patients with chronic hepatitis C.

Influence of the HCV subtype on the virological response to pegylated interferon and ribavirin therapy.

The hepatitis C virus genotype is considered to be the most important baseline predictor of a sustained virological response in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The influence of the subtype on the sustained virological response was investigated in patients infected with genotypes 1, 4, 5, or 6. This study was done on 597 patients with chronic hepatitis C who were given pegylated interferon and ribavirin for 48 weeks. The overall rate of sustained virological response in the 597 patients was 37.8%. Univariate analysis indicated that the sustained virological response of patients infected with subtype 1b (39%) tended to be higher than that of patients infected with subtype 1a (30.6%; P = 0.06) and it was similar to those patients infected with subtypes 4a (51.3%; P = 0.12) or 4d (51.7%; P = 0.16). Multivariate analysis indicated that five factors were independently associated with sustained virological response: the age (OR 0.97; 95% CI = 0.95–0.99), absence of cirrhosis (OR: 2.92; 95% CI = 1.7–5.0; P < 0.01), absence of HIV co‐infection (OR: 2.08; 95% CI = 1.2–3.5; P < 0.01), low baseline plasma HCV RNA concentration (OR: 1.74; 95% CI = 1.2–2.6; P < 0.01), and the subtype 1b (OR: 1.61; 95% CI = 1.0–2.5; P = 0.04) or subtypes 4a and 4d (OR: 2.03; 95% CI = 1.1–3.8; P = 0.03). In conclusion, among difficult‐to‐treat genotypes, the subtype 1a is associated with a lower response to anti‐HCV therapy than subtypes 1b, 4a, and 4d. J. Med. Virol. 81:2029–2035, 2009.

Epidemiology and long term survival of gastric carcinoma in the French district of Finistere between 1984 and 1995.

OBJECTIVES The aims of this study were to evaluate trends in incidence, clinical characteristics, treatment regimen and prognosis of gastric carcinoma in the area of Finistere (France) during a 12-year period. METHODS Between 1984 and 1995, the Finistere Registry of GastroIntestinal Tract Tumors listed 2 139 patients with gastric carcinoma in a population of 838 627 inhabitants. Curative resection and operative mortality were analyzed by logistic regression. Prognostic factors were determined using the Kaplan-Meier method and the Cox model. RESULTS When comparing the second period (1990-1995) to the first period (1984-1989) we observed: a) a decrease of standardized incidence (13.2 vs. 15.6/100 000 inhabitants/year in males and 5.4 vs. 7.0/100 000 inhabitants/year in females); b) a significant increase of linitis plastica (21.4% vs. 10.9%) and infiltrative tumors (53.1 vs. 31.2%) (P<0.0001); c) no variation in tumor stage at diagnosis; d) a significant increase in curative resection (65.7% vs. 45.0%; P<0.0001); e) no variation in operative mortality; f) the absence of improvement of survival rate; the latter was 29% at 2 years, 19% at 5 years and 11% at 10 years during the second period. Multivariate analysis showed that the main prognostic factors of gastric carcinoma were age, tumor stage and the type of surgical procedure. CONCLUSION This study showed a decrease in the incidence of gastric carcinoma over time and an increase of linitis plasticia and infiltrative forms. Despite improvement in management of patients, the global prognosis of gastric carcinoma did not improve significantly over a 12-year period of observation.

Prognostic Indices for Budd-Chiari Syndrome : Valid for Clinical Studies but Insufficient for Individual Management

OBJECTIVES:Several prognostic indices (PIs) have been proposed for Budd–Chiari syndrome (BCS). However, patient characteristics, causal factors, and treatment outcomes have changed since these indices have been elaborated. Validation in a recent patient population and comparison of predictive accuracy between these PIs are needed.METHODS:A database of 96 BCS patients diagnosed between 1995 and 2005 was analyzed. Cox survival models were fitted with time to liver transplantation or death, and time to invasive therapy or death, as end points. The prognostic values of known indices (Child–Pugh score, model for end-stage liver disease (MELD), Clichy, Rotterdam BCS index, New Clichy, and BCS–TIPS (transjugular intrahepatic portosystemic shunt)) at diagnosis were assessed in Cox models using the chi-square test, the Kent and O’Quigley measure of dependence, and unrestricted bootstrapping analysis. Areas under receiver operating characteristic curves (AUROCs) were built for both end points and compared.RESULTS:All prognostic indices, except BCS–TIPS, were significant predictors of transplant-free and invasive therapy–free survival. However, only 31 and 37% of the variance in transplant-free and invasive therapy–free survival, respectively, were explained by the best performing indices. For transplant-free survival, AUROCs were <0.70. For invasive therapy–free survival, AUROCs were <0.80. For both end points, BCS–TIPS PI AUROCs were significantly lower than others.CONCLUSIONS:Most PIs are valid for transplant-free survival and invasive therapy–free survival in a population of current BCS patients, and thus can be used for stratification in clinical studies. However, predictive accuracy is insufficient to be used for individual patients.

Impact of HFE genetic testing on clinical presentation of hereditary hemochromatosis: new epidemiological data

BackgroundHereditary hemochromatosis (HH) is a common inherited disorder of iron metabolism in Northern European populations. The discovery of a candidate gene in 1996 (HFE), and of its main mutation (C282Y), has radically altered the way to diagnose this disease. The aim of this study was to assess the impact of the HFE gene discovery on the clinical presentation and epidemiology of HH.MethodsWe studied our cohort of 415 patients homozygous for the C282Y allele and included in a phlebotomy program in a blood centre in western Brittany, France.ResultsIn this cohort, 56.9% of the patients were male and 21.9% began their phlebotomy program before the implementation of the genetic test. A significant decrease in the sex ratio was noticed following implementation of this DNA test, from 3.79 to 1.03 (p < 10-5), meaning that the proportion of diagnosed females relatives to males greatly increased. The profile of HH patients at diagnosis changed after the DNA test became available. Serum ferritin and iron values were lower and there was a reduced frequency of clinical signs displayed at diagnosis, particularly skin pigmentation (20.1 vs. 40.4%, OR = 0.37, p < 0.001) and hepatomegaly (11.0 vs. 22.7%, OR = 0.42, p = 0.006). In contrast, fatigue became a more common symptom at diagnosis (68.0 vs. 51.2%, OR = 2.03, p = 0.004).ConclusionThis study highlights the importance of the HFE gene discovery, which has simplified the diagnosis of HH and modified its clinical presentation and epidemiology. This study precisely measures these changes. Enhanced diagnosis of HFE-related HH at an early stage and implementation of phlebotomy treatment are anticipated to maintain normal life expectancy for these patients.

Antibody response of patients with Helicobacter pylori-related gastric adenocarcinoma: significance of anti-cagA antibodies.

ABSTRACT The aim of this study was to search for a specific antibody pattern in sera from patients suffering from Helicobacter pylori-related gastric adenocarcinoma (GAC). The serological response of 22 patients suffering from GAC, 31 patients with gastroduodenal ulcer, and 39 asymptomatic subjects was analyzed using immunoblotting performed with three H. pylori strains: strain ATCC 43579; strain B110, isolated from a patient with ulcers; and strain B225, isolated from a patient with GAC. In addition, the latex agglutination test Pyloriset Dry was used to analyze ambiguous sera. H. pylori seropositivity was 75% in the GAC group, 61.3% in the ulcer group, and 56.4% in the asymptomatic group. Anti-CagA antibodies were found more often in the GAC group (48.8%) and in the ulcer group (47.3%) than in the asymptomatic group (21.2%). These percentages depended on the strain used as an antigen: in the GAC group, the anti-CagA frequencies were 93.3, 40, and 13.3% with strains B225, B110, and ATCC 43579, respectively. Thus the presence of anti-CagA antibodies was increased in patients suffering from H. pylori-related GAC, in particular when the CagA antigen was from a GAC strain. These data suggest the existence of a CagA protein specifically expressed by H. pylori strains isolated from GAC patients.