Elisabeth Monnet

Geographical variations of inflammatory bowel disease in France: A study based on national health insurance data

Background and Aim: A north‐south gradient in inflammatory bowel disease (IBD) incidence has been found in Europe and the United States. Its existence is inferred from comparisons of registries that cover only small portions of territories. Several studies suggest that IBD incidence in the north has reached a plateau, whereas in the south it has risen sharply. This evolution tends to reduce the north‐south gradient, and it is uncertain whether it still exists. In France, patients with IBD are fully reimbursed for their health expenses by the national health insurance system, which is a potential source of data concerning the incidence of IBD at the national level. The aim of this study was to assess the geographical distribution of Crohns disease (CD) and ulcerative colitis (UC) in France and to test the north‐south gradient hypothesis. Methods: This study was conducted in metropolitan France and included patients to whom IBD reimbursement was newly attributed between January 1, 2000 and December 31, 2002. Data provided relate to age, sex, postcode area of residence, and IBD type. The mapping of geographical distribution of smoothed relative risks (RR) of CD and UC was carried out using a Bayesian approach, taking into account autocorrelation and population size in each département. Results: In the overall population, incidence rates were 8.2 for CD and 7.2 for UC per 100,000 inhabitants. A clear north‐south gradient was shown for CD. Départements with the highest smoothed RR were located in the northern third of France. By contrast, the geographical distribution of smoothed RR of UC was homogeneous. Conclusions: This study shows a north‐south gradient in France for CD but not for UC.

C-Reactive protein predicts short-term mortality in patients with cirrhosis

BACKGROUND & AIMS We aimed at improving prediction of short-term mortality in cirrhotic inpatients by evaluating C-reactive protein (CRP) as a surrogate marker of systemic inflammatory response syndrome (SIRS). METHODS One-hundred and forty-eight consecutive cirrhotic patients with Child-Pugh score ≥ B8 and without hepatocellular carcinoma were prospectively included and followed for 182 days. The primary end point was 6-month survival. RESULTS Main baseline characteristics were as follows: alcoholic liver disease in 88.5%; bacterial infection in 37%; hepatorenal syndrome in 7% of cases. CRP range was 1-240 mg/L (median 26 mg/L); 42 patients (28.4%) had SIRS as defined by ACCP/SCCM-criteria. CRP levels were higher in patients with SIRS (50 vs. 21 mg/L; p<0.0001), infection (46 vs. 27 mg/L; p<0.0001), and alcoholic hepatitis (44 vs. 32 mg/L, p=0.049). Forty-two patients died within the first 6 months of follow-up. Short-term mortality was associated with extrahepatic co-morbidities (p=0.002), high MELD score (p<0.001; AUROC=0.67), renal failure (p=0.008), elevated blood lactates (p<0.001), and high baseline CRP levels (p=0.003; AUROC=0.63; best cut-off value at 29 mg/L). Among patients with baseline CRP ≥ 29 mg/L, 32 still had CRP ≥ 29 mg/L at day 15 (group A). Group A was associated with 6-month mortality in the overall population (p<0.001) and also through sensitivity analyses restricted to patients without infection or alcoholic hepatitis. Multivariate analysis (Cox) adjusted for age identified three predictors of mortality: high MELD score (HR=1.08; 95% CI: 1.03-1.12; p<0.001), extrahepatic co-morbidities (HR=2.51; 95% CI: 1.31-4.84; p=0.006), and CRP level (group A) (HR=2.73; 95% CI: 1.41-5.26; p=0.003). The performance of the three variables taken together for predicting death was 0.80 (AUROC). CONCLUSIONS In Child-Pugh score ≥ B8 cirrhotic patients, persistent CRP levels ≥ 29 mg/L predicted short-term mortality independently of age, MELD, and co-morbidities, and better than infection or clinically-assessed SIRS.

LOW EXPOSURE TO SUNLIGHT IS A RISK FACTOR FOR CROHN?S DISEASE

Aliment Pharmacol Ther 2011; 33: 940–945

Predictive factors of alcohol relapse after orthotopic liver transplantation for alcoholic liver disease

OBJECTIVES The objective of this prospective study was to determine whether sociological and/or alcohol-related behavioral factors could be predictive of relapse after orthotopic liver transplantation for alcoholic liver disease. METHODS Fifty-five liver-transplanted patients out of a series of 120 alcoholic cirrhotic patients were enrolled in a randomized prospective study. This study was initially designed to compare the 2 year survival in intent-to-transplant patients versus in-intent-to-use conventional treatment patients. For all patients, an identical questionnaire was completed at inclusion, and every 3 months for 5 years to collect data on alcohol-related behavior factors. RESULTS Fifty-one patients fulfilled the criteria for the study. The mean follow-up was 35.7 months (range: 1-86). Rate of alcohol relapse was 11% at one year and 30% at 2 years. Alcohol intake above 140 g a week was declared by 11% and 22% of patients at one and 2 years, respectively. The only variable leading to a significantly lower rate of relapse was abstinence for 6 months or more before liver transplantation (23% vs 79%, P=0.0003). This variable was also significant for patients whose alcohol intake was greater than 140 g per week (P=0.003) (adjusted relative risk=5.5; 95%CI=1.3-24.5; P=0.02). Multivariate analysis (Cox model) showed that abstinence for 6 months or more before liver transplantation was the unique predictive variable. CONCLUSION In this prospective study of 51 patients transplanted for alcoholic liver disease, abstinence before liver transplantation was the only predictive factor of alcohol relapse after liver transplantation.

Environmental risk factors in Crohn's disease and ulcerative colitis: an update

Rapid increase in Crohns disease (CD) and ulcerative colitis (UC) incidence in developed countries, occurrence of CD in spouses and lack of complete concordance in monozygotic twins are strong arguments for the role of environmental factors in inflammatory bowel disease (IBD). Only two environmental factors have an established role in IBD. Smoking is a risk factor for CD and a protective factor for UC; appendectomy is a protective factor for UC. Many other environmental factors for IBD have been investigated. These are infectious agents, diet, drugs, stress and socio-economic factors. They are detailed in this paper. Among them, adherent invasive E. coli, infectious gastroenteritis, oral contraceptives and antibiotics could play a role in CD. To date, three theories integrate environmental factors to pathogenesis of IBD: hygiene, infection and cold chain. Much work remains to be done to identify risk factors for IBD. As exemplified by smoking, research of environmental risk factors of IBD is useful since it may lead to an improved disease course among patients and perhaps, to appropriate prevention among predisposed subjects. Further studies in this field are eagerly awaited.

Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial

BACKGROUND & AIMS Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial. METHODS A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1g/kg on day 3; albumin group [ALB]: n=96) or antibiotics alone (control group [CG]: n=97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 μmol/L). The secondary endpoint was 3-month survival rate. RESULTS Forty-seven (24.6%) patients died (ALB: n=27 vs. CG: n=20; 3-month survival: 70.2% vs. 78.3%; p=0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p=0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p=0.88). By multivariate analysis, MELD score (p<0.0001), pneumonia (p=0.0041), hyponatremia (p=0.031) and occurrence of renal failure (p<0.0001) were predictors of death. Of note, pulmonary edema developed in 8/96 (8.3%) patients in the albumin group of whom two died, one on the day and the other on day 33 following albumin infusion. CONCLUSIONS In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients.

Longitudinal study of respiratory health in dairy farmers: influence of artificial barn fodder drying

Factors influencing respiratory consequences of dairy farming have not been extensively investigated to date. To evaluate the effects of barn fodder drying on respiratory symptoms and lung function, a 5 yr follow-up study was performed in the Doubs (France). A cohort of male dairy farmers was analysed in 1990. The initial cross-sectional results suggested that barn-drying fodder may protect dairy farmers from lung function impairment. In 1995, 113 barn-drying farmers (92%) and 231 traditional-drying farmers (84%) were re-analysed. Barn and traditional fodder-drying farmers were compared for prevalence of symptoms and spirometric measures of lung function. After controlling for age, smoking status, altitude and cumulative exposure, barn-drying farmers compared to traditional-drying farmers had a lower prevalence of chronic bronchitis (4 versus 10%; p<0.05) and slightly higher values of forced expiratory volume in one second (FEV1) (p=0.06) and FEV1/vital capacity (VC) (p<0.01). Nevertheless, decline of the respiratory function parameters was not significantly different between the two groups. Variables positively and significantly associated to longitudinal decline of lung function parameters were: age (FEV1, FEV1/VC); altitude (VC, FEV1) and chronic bronchitis and dyspnoea at the initial survey (FEV1/VC). Persistence and emergence of chronic bronchitis, dyspnoea and symptoms at exposure were also significantly associated to an acceleration in the annual decline of the respiratory function. In conclusion, the mode of fodder drying does not seem to significantly influence the decline in lung function. Nevertheless, this study confirms the results of the initial cross-sectional analysis and supports the hypothesis that barn drying fodder may have a protective effect on respiratory health in dairy farming.

Pathologic complete response to preoperative chemotherapy predicts cure in early-stage non-small-cell lung cancer: combined analysis of two IFCT randomized trials.

Introduction: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non–small-cell lung cancer (NSCLC) after neoadjuvant chemotherapy resulted in improved outcome, and to determine predictive factors for pCR. Methods: Eligible patients with stage-IB or -II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique phase-III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. Results: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival was 80.0% compared with 55.8% in the non-pCR group (p = 0.0007). In multivariate analyses, pCR was a favorable prognostic factor of overall survival (relative risk = 0.34; 95% confidence interval = 0.18–0.64) in addition to squamous-cell carcinoma, weight loss less than or equal to 5%, and stage-IB disease. Five-year disease-free survival was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p < 0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (odds ratio [OR] = 4.30; 95% confidence interval = 1.90–9.72). Conclusion: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in stage-IB–II NSCLC. Our study is the largest published series evaluating pCRs after preoperative chemotherapy. The only factor predictive of pCR was squamous-cell carcinoma. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.

Fine‐scale geographic variations of inflammatory bowel disease in France: Correlation with socioeconomic and house equipment variables

Background:In a previous study we found a north–south gradient for Crohns disease (CD) incidence in France. The aim of the present study was to determine if socioeconomic factors may influence the geographic distribution of CD and ulcerative colitis (UC) in France. Methods:Using the national health insurance databases, incidence rates of CD and UC were estimated for each of 341 metropolitan “job areas” in 2000–2002. Relationships between incidence rates and relevant contextual variables from the 1999 French census were tested for significance using a Poisson regression. Mapping of smoothed relative risks (sRR) for CD and UC at the scale of job areas, using a Bayesian approach and adjusting for significant contextual variables, was carried out in order to search for geographic variations. Results:CD incidence rates were negatively related to the percentage of farmers and to the percentage of housing with bathroom and toilets and positively related to the unemployment rate and to the percentage of households below the poverty threshold. Mapping of sRR for CD showed a clear north–south gradient, which was slightly improved after including the percentage of farmers and the percentage of housing with toilets. In UC we found no significant correlation between either incidence and socioeconomic variables or incidence and house equipment variables, and there was no north–south gradient. However, there was a positive and significant correlation between CD and UC incidence. Conclusions:The present study shows that geographic risk factors of CD in France are northern latitude, nonrural areas, and areas with poor sanitary house equipment. Among these factors the most important is northern latitude. (Inflamm Bowel Dis 2009)

Assessment of adrenal function in cirrhotic patients using concentration of serum-free and salivary cortisol

Objective: Because over 90% of serum cortisol is bound to albumin and corticosteroid‐binding globulin (CBG), changes in these proteins can affect measures of serum total cortisol levels in cirrhotics without altering serum‐free and salivary cortisol concentrations.