Laurent Peyrin-Biroulet

Publications of Laurent Peyrin-Biroulet

• Long-term outcome after first intestinal resection in pediatric-onset Crohn's disease: A population-based study.

  Authors: Médina Boualit, Julia Salleron, Dominique Turck, Mathurin Fumery, Guillaume Savoye, Jean-Louis Dupas, Eric Lerebours, Alain Duhamel, Véronique Merle, Antoine Cortot, Jean-Frédéric Colombel, Laurent Peyrin-Biroulet, Corinne Gower-Rousseau

  Inflammatory bowel diseases. 05/2012;

  BACKGROUND: To describe long-term postoperative evolution of pediatric-onset Crohn's disease (CD) and identify predictors of outcome we studied a population-based cohort (1988-2004) of 404 patientsBACKGROUND: To describe long-term postoperative evolution of pediatric-onset Crohn's disease (CD) and identify predictors of outcome we studied a population-based cohort (1988-2004) of 404 patients (0-17 years), of which 130 underwent surgery. METHODS: Risks for a second resection and first need for immunosuppressors (IS) and/or biologics were estimated by survival analysis and Cox models used to determine predictors of outcome. Impact of time of first surgery on nutritional catch-up was studied using regression. RESULTS: In all, 130 patients (70 females) with a median age at diagnosis of 14.2 years (interquartile range: 12-16) were followed for 13 years (9.4-16.6). Probability of a second resection was 8%, 17%, and 29% at 2, 5, and 10 years, respectively. In multivariate analysis, age <14, stenosing (B2) and penetrating (B3) behaviors and upper gastrointestinal location (L4) at diagnosis were associated with an increased risk of second resection. Probability of receiving IS or biologics was 18%, 34%, and 47% at 2, 5, and 10 years, respectively. In multivariate analysis, L4 was a risk factor for requiring IS or biologics, while surgery within 3 years after CD diagnosis was protective. Catch-up in height and weight was better in patients who underwent surgery within 3 years after CD diagnosis than those operated on later. CONCLUSIONS: In this pediatric-onset CD study, mostly performed in a prebiologic era, a first surgery performed within 3 years after CD diagnosis was associated with a reduced need for IS and biologics and a better catch-up in height and weight compared to later surgery. (Inflamm Bowel Dis 2012;).

• IBD: Mucosal healing-EXTENDing our knowledge in Crohn's disease.

  Authors: Silvio Danese, Laurent Peyrin-Biroulet

  Nature reviews. Gastroenterology & hepatology. 04/2012;

• Methyl donor deficiency impairs fatty acid oxidation through PGC-1α hypomethylation and decreased ER-α, ERR-α and HNF-4α in rat liver.

  Authors: Shabnam Pooya, Sébastien Blaise, Maira Moreno Garcia, Jean Giudicelli, Jean-Marc Alberto, Rosa-Maria Guéant-Rodriguez, Elise Jeannesson, Naig Gueguen, Aude Bressenot, Bénédicte Nicolas, Yves Malthiery, Jean-Luc Daval, Laurent Peyrin-Biroulet, Jean-Pierre Bronowicki, Jean-Louis Guéant

  Journal of hepatology. 04/2012;

  BACKGROUND: Folate and cobalamin are methyl donors needed for synthesizing methionine, which is the precursor of S-adenosylmethionine, the substrate of methylation in epigenetic and epigenomicBACKGROUND: Folate and cobalamin are methyl donors needed for synthesizing methionine, which is the precursor of S-adenosylmethionine, the substrate of methylation in epigenetic and epigenomic pathways. Methyl donor deficiency produces liver steatosis and predisposes to metabolic syndrome. Whether impaired fatty acid oxidation contributes to this steatosis remains unknown. METHODS: We evaluated the consequences of methyl donor deficient diet in liver of pups from dams subjected to deficiency during gestation and lactation. RESULTS: The deprived rats had microvesicular steatosis, with increased triglycerides, decreased methionine synthase activity, S-adenosylmethionine and S-adenosylmethionine/S-adenosylhomocysteine ratio. We observed no change in apoptosis markers, oxidant and reticulum stresses, and carnityl-palmitoyl transferase1 activity and a decreased expression of SREBP-1c. Impaired beta-oxidation of fatty acids and carnitine deficit were the predominant changes, with decreased free and total carnitines, increased C14:1/C16 acylcarnitine ratio, decrease of oxidation rate of palmitoyl-CoA and palmitoyl-L-carnitine and decrease of expression of novel organic cation transporter 1, acylCoA-dehydrogenase and trifunctional enzyme subunit alpha and decreased activity of complexes I and II. These changes were related to lower protein expression of ER-α, ERR-α and HNF-4α and hypomethylation of PGC-1α co-activator that reduced its binding with PPAR-α, ERR-α and HNF-4α. CONCLUSION: The liver steatosis resulted predominantly from hypomethylation of PGC1-α, decreased binding with its partners and subsequent impaired mitochondrial fatty acid oxidation. This link between methyl donor deficiency and epigenomic deregulations of energy metabolism opens new insights on pathogenesis of fatty liver disease, in particular in relation with the foetal programming hypothesis. (250 words).

• Tolerability of one hour 10mg/kg infliximab infusions in patients with inflammatory bowel disease.

  Authors: Abdenour Babouri, Anthony Buisson, Marc-André Bigard, Laurent Peyrin-Biroulet

  Journal of Crohn's & colitis. 04/2012;

  BACKGROUND AND AIM: In patients with inflammatory bowel disease (IBD) tolerating 2-h infusions of 5mg/kg infliximab scheduled maintenance therapy, the infusion time can be shortened to 1-h with goodBACKGROUND AND AIM: In patients with inflammatory bowel disease (IBD) tolerating 2-h infusions of 5mg/kg infliximab scheduled maintenance therapy, the infusion time can be shortened to 1-h with good tolerability. The tolerability of one 1-hour 10mg/kg infliximab infusion in patients with IBD is unknown. METHODS: Between August and September 2011, 8 patients received one 1-hour 10mg/kg infliximab infusion. All patients were treated in our infusion unit under standard operating procedures. Intravenous steroid premedication was given to all patients. These 8 patients were compared to 26 IBD patients who received one 1-hour 5mg/kg infliximab infusion during the same study period at Nancy University Hospital. The charts of these 34 patients were reviewed to assess tolerability of 1-hour infliximab infusions. RESULTS: A total of 34 patients with IBD on infliximab maintenance therapy (82.4% Crohn's disease, 17.6% ulcerative colitis; 22 females) received one 1-hour 5 or 10mg/kg infusion. Four patients were receiving concomitant immunomodulators. No severe infusions reactions were reported in the 34 IBD patients. Two mild acute reactions (7.7%) and two delayed reactions (7.7%) occurred in the 5mg/kg infliximab group. We did not observe any acute or delayed infliximab reactions in the 10mg/kg patients group. CONCLUSIONS: In patients with inflammatory bowel disease receiving infliximab scheduled maintenance therapy, 1-hour infusion time for 10mg/kg infliximab appears to be well tolerated. Large prospective studies are needed to confirm our findings.

• Dietary beliefs and behavior among inflammatory bowel disease patients.

  Authors: Camille Zallot, Didier Quilliot, Jean-Baptiste Chevaux, Carina Peyrin-Biroulet, Rosa Maria Guéant-Rodriguez, Estelle Freling, Benjamin Collet-Fenetrier, Nicolas Williet, Olivier Ziegler, Marc-André Bigard, Jean-Louis Guéant, Laurent Peyrin-Biroulet

  Inflammatory bowel diseases. 03/2012;

  BACKGROUND: We investigated dietary beliefs and behavior in a large population of adult inflammatory bowel disease (IBD) patients and evaluated their impact on patients' social life. METHODS: ABACKGROUND: We investigated dietary beliefs and behavior in a large population of adult inflammatory bowel disease (IBD) patients and evaluated their impact on patients' social life. METHODS: A questionnaire of 14 items was administered to all consecutive IBD patients followed at the Nancy University Hospital Department of Gastroenterology from February to July 2011. RESULTS: A total of 244 patients participated in the survey; 15.6% (n = 38) of patients believed that diet could initiate the disease, while 57.8% (n = 141) believed that food can play a role in causing a relapse. Forty percent (107/244) of patients identified food as a risk factor for relapse. Seventy-three percent of respondents reported having already received nutritional advice. The majority of respondents (47.5%, n = 116) reported that the disease had changed the pleasure of eating. Only one-quarter of patients had a normal diet in case of relapse. Almost two out of three patients (66.8%, n = 163) reported not eating certain foods they usually like to eat in order to prevent a relapse. Dietary beliefs and behavior had an impact on their social life for one-fifth of patients. Excluding food was associated with refusing outdoor dining for fear of causing relapse (P = 0.006) and not sharing the same menu as the other members of the family living under the same roof (P = 0.002). CONCLUSIONS: The majority of IBD patients are avoiding certain foods. Dietary beliefs and behavior have a strong impact on their social life. (Inflamm Bowel Dis 2012;).

• Colorectal cancer in inflammatory bowel diseases: A population-based study (1976-2008).

  Authors: Laurent Peyrin-Biroulet, Côme Lepage, Valérie Jooste, Jean-Louis Guéant, Jean Faivre, Anne-Marie Bouvier

  Inflammatory bowel diseases. 03/2012;

  BACKGROUND: Few data are available on the incidence, characteristics, treatment, and prognosis of inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) in population-based cohorts.BACKGROUND: Few data are available on the incidence, characteristics, treatment, and prognosis of inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) in population-based cohorts. METHODS: Among the 19,451 new cases of CRC recorded in the Burgundy digestive cancer registry between 1976 and 2008, all cases of IBD-associated CRC were identified. Incidence rates were age-standardized according to the world standard population. Prognosis was determined using univariate and multivariate relative survival. RESULTS: Thirty-eight IBD-associated CRC were identified (ulcerative colitis, n = 29; Crohn's disease, n = 9). The mean age at CRC diagnosis was greater for patients without IBD than those with IBD (70.9 vs. 56.9 years, respectively; P < 0.001). Distributions of gender, stage at presentation, location, and histological type of CRC did not differ from those of sporadic cases. The overall world age-standardized incidence of IBD-associated CRC per 100,000 was 0.11 (standard deviation [SD]: 0.03) for men and 0.06 (SD: 0.02) for women. Only age was independently associated with IBD-associated CRC (odds ratio [OR]: 0.22; 95% confidence interval [CI]: 0.12-0.43; P < 0.001). Treatment modalities did not differ between IBD and non-IBD patients. Five-year relative survival was 51.9% (95% CI: 51.1-52.8%) in non-IBD patients and 41.3% (95% CI: 24.6-57.2%) in IBD patients (P = 0.201). After adjustment for age, gender, and stage at diagnosis, the excess hazard of death was 1.46 times higher in IBD than in non-IBD patients (95% CI: 0.94-2.27; P = 0.070). CONCLUSIONS: Apart from age, the characteristics of IBD-associated CRC were similar to those of non-IBD CRC. The prognosis of CRC may be poorer in patients with IBD than in those without IBD. (Inflamm Bowel Dis 2012;).

• Plasma soluble triggering receptor expressed on myeloid cells-1 in Crohn's disease.

  Authors: Vincent Billioud, Sébastien Gibot, Frédéric Massin, Abderrahim Oussalah, Jean-Baptiste Chevaux, Nicolas Williet, Jean-Pierre Bronowicki, Marc-André Bigard, Jean-Louis Guéant, Laurent Peyrin-Biroulet

  Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 02/2012;

  BACKGROUND: No definite conclusions can be drawn from available data on the accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to assess disease activity in Crohn'sBACKGROUND: No definite conclusions can be drawn from available data on the accuracy of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) to assess disease activity in Crohn's disease. AIMS: Plasma sTREM-1 levels were correlated with disease activity markers in Crohn's disease. METHODS: 191 consecutive patients from a single referral centre (Nancy IBD cohort) were prospectively enrolled between June 1, 2005 and December 12, 2008. Plasma sTREM-1 levels were also assessed amongst 20 healthy controls. RESULTS: The sTREM-1 was detectable in 87 Crohn's disease patients (46%). Plasma sTREM-1 level was higher in Crohn's disease patients (interquartile range, 0-356) than in healthy controls (interquartile range, 0-15.1; P=0.01). It was neither correlated with Crohn's disease activity index (r=0.05, P=0.56), C-reactive protein (r=0.06, P=0.53), nor with albumin (r=-0.041, P=0.66). Crohn's disease activity index, C-reactive protein and albumin median levels were similar between patients with positive sTREM-1 levels and those with undetectable sTREM-1 levels. Azathioprine (P=0.06), infliximab (P=0.68) and methotrexate (P=0.56) did not influence sTREM-1 levels. CONCLUSION: Plasma sTREM-1 does not appear to be an accurate marker of disease activity in Crohn's disease and cannot be recommended for assessing disease activity in these patients.

• Helicobacter pylori serologic status has no influence on the association between fucosyltransferase 2 polymorphism (FUT2 461 G->A) and vitamin B-12 in Europe and West Africa.

  Authors: Abderrahim Oussalah, Cyril Besseau, Céline Chery, Elise Jeannesson, Rosa-Maria Guéant-Rodriguez, Guido Anello, Paolo Bosco, Maurizzio Elia, Antonino Romano, Jean-Pierre Bronowicki, Philippe Gerard, Justine Paoli, Patrice Hodonou Avogbe, Nicodème Chabi, Ambaliou Sanni, Emile Amouzou, Laurent Peyrin-Biroulet, Jean-Louis Guéant

  The American journal of clinical nutrition. 02/2012; 95(2):514-21.

  Genomewide association studies have shown a relation between plasma vitamin B-12 concentration and the 461G→A polymorphism of fucosyltransferase 2 (FUT2), a gene associated with susceptibility toGenomewide association studies have shown a relation between plasma vitamin B-12 concentration and the 461G→A polymorphism of fucosyltransferase 2 (FUT2), a gene associated with susceptibility to Helicobacter pylori infection. We evaluated in 2 populations the association of FUT2 461 G→A polymorphism with vitamin B-12 and related metabolic markers and investigated whether the influence of FUT2 on H. pylori serology is part of the mechanisms that underlie these associations. The study included 1282 ambulatory subjects from Europe and West Africa. Blood concentrations of vitamin B-12, folate, homocysteine, and methylmalonic acid were measured. Genotyping was performed by real-time polymerase chain reaction. H. pylori serology testing was performed by using ELISA. In univariate analysis, FUT2 461 A/A genotype was associated with higher plasma vitamin B-12 concentration in the total population (P = 0.0007) as well as in Europe (P = 0.0009) and in West Africa (P = 0.0015). Positivity for H. pylori serology was higher in West Africa (P < 0.0001) and was not associated with low plasma vitamin B-12. The prevalence of H. pylori-positive patients did not differ among FUT2 461 G→A genotypes (P = 0.2068). In multivariate analysis, FUT2 461 G→A genotype (P = 0.0008), but not positive H. pylori serology, was an independent predictor of plasma vitamin B-12 concentration. This study confirms the influence of FUT2 461 G→A polymorphism on plasma vitamin B-12 concentration and showed no influence of H. pylori serologic status on this association in ambulatory subjects from Europe and West Africa.

• Implementing changes in clinical practice to improve the management of Crohn's disease.

  Authors: Remo Panaccione, Toshifumi Hibi, Laurent Peyrin-Biroulet, Stefan Schreiber

  Journal of Crohn's & colitis. 02/2012; 6 Suppl 2:S235-42.

  The introduction of anti-tumour necrosis factor therapies has provided highly effective treatments for Crohn's disease, making it possible to significantly improve the prognosis of patients. However,The introduction of anti-tumour necrosis factor therapies has provided highly effective treatments for Crohn's disease, making it possible to significantly improve the prognosis of patients. However, neither conventional non-biological therapies nor anti-tumour necrosis factor therapies are routinely used to optimum effect. There are several reasons for this, including a lack of specific evidence to guide common clinical questions and a lack of clearly defined treatment targets. This paper suggests some simple changes to the management of Crohn's disease that have the potential to significantly improve patient outcomes. A new treatment target, 'deep remission', which includes mucosal healing as well as clinical remission, may be the first step in defining the successful treatment of Crohn's disease; early clinical studies have demonstrated that this is a readily achievable target. Initiating appropriate treatment early can increase clinical remission rates, improve steroid sparing, induce mucosal healing and prevent structural bowel damage, whereby reducing the need for hospitalization and surgery. There are also clear indications that modifying treatment based on regular objective assessments of disease activity to provide tight disease control can improve patient outcomes in a similar way to that observed in rheumatoid arthritis. These simple changes to management strategy appear to allow the full potential of available treatments to be realized. Clinical studies to further define optimized treatment strategies for Crohn's disease are underway and will provide future direction.

• Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease.

  Authors: Harry Sokol, Laurent Beaugerie, Marc Maynadié, David Laharie, Jean-Louis Dupas, Bernard Flourié, Eric Lerebours, Laurent Peyrin-Biroulet, Matthieu Allez, Tabassome Simon, Fabrice Carrat, Nicole Brousse

  Inflammatory bowel diseases. 01/2012;

  BACKGROUND: It remains to be shown whether inflammatory bowel disease (IBD) is associated with an increased risk of primary intestinal lymphoproliferative disorders (PILD). We assessed this risk inBACKGROUND: It remains to be shown whether inflammatory bowel disease (IBD) is associated with an increased risk of primary intestinal lymphoproliferative disorders (PILD). We assessed this risk in the CESAME French nationwide prospective observational cohort. METHODS: In all, 680 gastroenterologists enrolled 19,486 patients with IBD (Crohn's disease in 60.3%) from May 2004 to June 2005. Follow-up ended on 31 December 2007. Available biopsy samples and surgical specimens from patients with PILD (n = 14) were centralized for review. The reference incidence of PILD in the general population was obtained from the Côte d'Or registry and was used as a comparator to assess the standardized incidence ratio (SIR). The influence of thiopurine exposure was explored in a nested case-control study. RESULTS: In the CESAME population the crude incidence of PILD was 0.12/1000 patient-years, with a corresponding SIR of 17.51 (95% confidence interval [CI], 6.43-38.11; P < 0.0001). The risk was highest in patients exposed to thiopurines (SIR 49.52, 95% CI 13.49-126.8; P < 0.0001), while it did not reach statistical significance in patients naïve to thiopurines (SIR 4.83, 95% CI, 0.12-26.91; P = 0.37). The odds ratio associated with ongoing thiopurine exposure (vs. naïve) was 2.97 (95% CI, 0.30-infinity; P = 0.38). All 14 cases of PILD were non-Hodgkin's B-cell LD, 78.6% occurred in males, 85.7% arose in IBD lesions, and 45.5% were Epstein-Barr virus-positive. Eleven cases occurred in patients with Crohn's disease. Mean (SD) age at PILD diagnosis was 55.1 (5.6) years and the median time since IBD onset was 8.0 years (interquartile range, 3.0-15.8). CONCLUSIONS: Patients with IBD have an increased risk of developing PILD. (Inflamm Bowel Dis 2012;).

• Diagnosis, prevention and treatment of postoperative Crohn's disease recurrence.

  Authors: Anthony Buisson, Jean-Baptiste Chevaux, Gilles Bommelaer, Laurent Peyrin-Biroulet

  Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 01/2012;

  Ileocolonoscopy remains the gold standard in diagnosing postoperative recurrence. After excluding stricture, wireless capsule endoscopy seemed accurate in small series, but no validated score isIleocolonoscopy remains the gold standard in diagnosing postoperative recurrence. After excluding stricture, wireless capsule endoscopy seemed accurate in small series, but no validated score is available. Ultrasonography is a non-invasive diagnostic method reducing radiation exposure and emerging as an alternative tool for identifying post-operative recurrence. Computed tomography enteroclysis yields objective morphologic criteria that help differentiate between recurrent disease and fibrostenosis at the anastomotic site, but ionising radiation exposure limits its use. Magnetic resonance imaging may be equally powerful than ileocolonoscopy in diagnosing postoperative recurrence and in predicting the clinical outcome using specific MR-scores. Biomarkers such as faecal calprotectin and faecal lactoferrin showed promising results, but their specificity in the postoperative period will require further investigation. Numerous medications have tested to prevent and/or to treat postoperative recurrence. Efficacy of mesalamine is very low and comparable to placebo in most series. Thiopurines have modest efficacy in the postoperative setting and are associated with a high rate of adverse events leading to drug withdrawal. Antibiotics such as metronidazole or ornidazole may be effective, but toxicity and drug resistance prevent their long-term use. Anti-Tumour Necrosis Factor therapy is the most potent drug class to prevent and to treat postoperative recurrence in Crohn's disease.

• Prevalence of cytomegalovirus infection in steroid-refractory Crohn's disease.

  Authors: Xavier Roblin, Sylvie Pillet, Philippe Berthelot, Emilie Del Tedesco, Jean-Marc Phelip, Marie-Laure Chambonnière, Laurent Peyrin-Biroulet, Bruno Pozzetto

  Inflammatory bowel diseases. 01/2012;

• Ulcerative colitis as a progressive disease: The forgotten evidence.

  Authors: Joana Torres, Vincent Billioud, David B Sachar, Laurent Peyrin-Biroulet, Jean-Frédéric Colombel

  Inflammatory bowel diseases. 12/2011;

  In the management of Crohn's disease, earlier aggressive treatment is becoming accepted as a strategy to prevent or retard progression to irreversible bowel damage. It is not yet clear, however, ifIn the management of Crohn's disease, earlier aggressive treatment is becoming accepted as a strategy to prevent or retard progression to irreversible bowel damage. It is not yet clear, however, if this same concept should be applied to ulcerative colitis. Hence, we review herein the long-term structural and functional consequences of this latter disease. Disease progression in ulcerative colitis takes six principal forms: proximal extension, stricturing, pseudopolyposis, dysmotility, anorectal dysfunction, and impaired permeability. The precise incidence of these complications and the ability of earlier, more aggressive treatment to prevent them have yet to be determined. (Inflamm Bowel Dis 2011;).

• Identification of areas of functioning and disability addressed in inflammatory bowel disease-specific patient reported outcome measures.

  Authors: Ulrike Achleitner, Michaela Coenen, Jean-Frédéric Colombel, Laurent Peyrin-Biroulet, Narine Sahakyan, Alarcos Cieza

  Journal of Crohn's & colitis. 12/2011;

  BACKGROUND AND AIMS: Patient-reported outcome measures (PROMs) make it possible to assess health-status problems from the perspective of persons suffering from a disease. The objective of the paperBACKGROUND AND AIMS: Patient-reported outcome measures (PROMs) make it possible to assess health-status problems from the perspective of persons suffering from a disease. The objective of the paper is to examine and compare the contents of PROMs related to IBD based on the World Health Organization's International Classification of Functioning, Disability and Health (ICF) as the frame of reference. METHODS: A systematic literature review (1999-2009) in the databases Medline, EMBASE, PsycINFO, CINAHL and CENTRAL was performed to select IBD-specific PROMs. Abstracts and full-text articles were checked applying predefined eligibility criteria; IBD-specific PROMs were identified. The contents of the identified PROMs were examined by linking the items to ICF categories. The linked ICF categories of the PROMs were then compared. RESULTS: The review resulted in the selection of eight IBD-specific PROMs (e.g., Cleveland Global Quality of Life, Inflammatory Bowel Disease Quality of Life Questionnaire, Inflammatory Bowel Disease Questionnaire-32, Rating Form of IBD Patient Concerns, Short Inflammatory Bowel Disease Questionnaire). In total, 129 items were identified, the majority of which (n=90; 69.8%) could be linked to specific ICF categories. None of the linked categories were contained in all PROMs. The most frequently identified categories were 'b1300 Energy level', 'b5254 Flatulence', 'd910 Community life' and 'd920 Recreation and leisure'. CONCLUSION: The present study provides an overview of IBD-specific PROMs and their items. The results of the content comparison provide valuable information to facilitate and account for the selection of appropriate PROMs for different purposes of data collection in clinical and research settings.

• Incidence of and impact of medications on colectomy in newly diagnosed ulcerative colitis in the era of biologics.

  Authors: Nicolas Williet, Claire Pillot, Abderrahim Oussalah, Vincent Billioud, Jean-Baptiste Chevaux, Laurent Bresler, Marc-André Bigard, Jean-Louis Gueant, Laurent Peyrin-Biroulet

  Inflammatory bowel diseases. 12/2011;

  BACKGROUND: The cumulative incidence of colectomy and the impact of 5-aminosalicylates (5-ASA), azathioprine, and antitumor necrosis factor (TNF) treatment on the long-term need for surgery areBACKGROUND: The cumulative incidence of colectomy and the impact of 5-aminosalicylates (5-ASA), azathioprine, and antitumor necrosis factor (TNF) treatment on the long-term need for surgery are unknown in ulcerative colitis (UC) in the era of biologics. METHODS: This was an observational study of a referral center cohort. The cumulative incidence of UC-related colectomy was estimated using the Kaplan-Meier method. Independent predictors of surgery were identified using Cox proportional hazards regression with propensity scores adjustment. The electronic charts of 151 incident cases of UC from Nancy University Hospital, France, diagnosed between 2000 and 2008, were reviewed through January 2010. RESULTS: The median follow-up time per patient was 58 months. Twenty-one (14%) underwent surgery. The cumulative probabilities of colectomy were respectively 1.3% and 13.5% at 1 and 5 years from the time of diagnosis. The probability of receiving oral mesalamine at 5 years was 68.1%. The corresponding figures were 48.9% for azathioprine and 29.0% for infliximab. For corticosteroids, methotrexate, and cyclosporin these figures were 75%, 8.8%, and 11.5%, respectively. Using multivariate Cox proportional hazards regression analysis after propensity score adjustment, previous use of cyclosporin was the only independent predictor for colectomy (hazard ratio = 4.41; 95% confidence interval 1.75-1.13). CONCLUSIONS: About one-tenth of patients still require colectomy for UC at 5 years in the era of biologics. Oral 5-ASA, azathioprine, and anti-TNF therapy are not associated with a reduced need for colectomy. (Inflamm Bowel Dis 2011;).

• Results from the 2nd Scientific Workshop of the ECCO. I: Impact of mucosal healing on the course of inflammatory bowel disease.

  Authors: Laurent Peyrin-Biroulet, Marc Ferrante, Fernando Magro, Simon Campbell, Denis Franchimont, Herma Fidder, Hans Strid, Sandro Ardizzone, Gigi Veereman-Wauters, Jean-Baptiste Chevaux, Mathieu Allez, Silvio Danese, Andreas Sturm

  Journal of Crohn's & colitis. 10/2011; 5(5):477-83.

  Over the past years, mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases. Accumulating evidence indicates that mucosal healing may change theOver the past years, mucosal healing has emerged as a major therapeutic goal in clinical trials in inflammatory bowel diseases. Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalization rates in both ulcerative colitis and Crohn's disease. Mucosal healing may also prevent the development of long-term disease complications, such as bowel damage in Crohn's disease and colorectal cancer in ulcerative colitis. Histologic healing may be the ultimate therapeutic goal in ulcerative colitis, whereas its impact on the course of Crohn's disease is unknown. Complete mucosal healing may be required before considering drug withdrawal. Targeting early Crohn's disease is more effective than approaches aimed at healing mucosa in longstanding disease. Several questions remain to be answered: should mucosal healing be systematically used in clinical practice? Should we optimize therapies to achieve mucosal healing? What is the degree of intestinal healing that is required to change the disease course? Large prospective studies addressing these issues are needed.

• Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease.

  Authors: Laurent Peyrin-Biroulet, Florent Gonzalez, Laurent Dubuquoy, Christel Rousseaux, Caroline Dubuquoy, Cécilia Decourcelle, Alain Saudemont, Mickael Tachon, Elodie Béclin, Marie-Françoise Odou, Christel Neut, Jean-Frédéric Colombel, Pierre Desreumaux

  Gut. 09/2011; 61(1):78-85.

  Objective: Mesenteric fat hyperplasia is a hallmark of Crohn's disease (CD), and C reactive protein (CRP) is correlated with disease activity. The authors investigated whether mesenteric adipocytesObjective: Mesenteric fat hyperplasia is a hallmark of Crohn's disease (CD), and C reactive protein (CRP) is correlated with disease activity. The authors investigated whether mesenteric adipocytes may be a source of CRP in CD and whether inflammatory and bacterial triggers may stimulate its production by adipocytes. CRP expression in the mesenteric and subcutaneous fats of patients with CD and the correlation between CRP plasma concentrations and mesenteric messenger RNA (mRNA) levels were assessed. The impact of inflammatory and bacterial challenges on CRP synthesis was tested using an adipocyte cell line. Bacterial translocation to mesenteric fat was studied in experimental models of colitis and ileitis and in patients with CD. CRP expression was increased in the mesenteric fat of patients with CD, with mRNA levels being 80 ± 40 (p<0.05) and 140 ± 65 (p=0.04) times higher than in the mesenteric fat of patients with ulcerative colitis and in the subcutaneous fat of the same CD subjects, respectively, and correlated with plasma levels. Escherichia coli (1230 ± 175-fold, p<0.01), lipopolysaccharide (26 ± 0.5-fold, p<0.01), tumour necrosis factor α (15 ± 0.3-fold, p<0.01) and interleukin-6 (10 ± 0.7-fold, p<0.05) increased CRP mRNA levels in adipocyte 3T3-L1 cells. Bacterial translocation to mesenteric fat occurred in 13% and 27% of healthy and CD subjects, respectively, and was increased in experimental colitis and ileitis. Human mesenteric adipocytes constitutively expressed mRNA for TLR2, TLR4, NOD1 and NOD2. Mesenteric fat is an important source of CRP in CD. CRP production by mesenteric adipocytes may be triggered by local inflammation and bacterial translocation to mesenteric fat, providing a mechanism whereby mesenteric fat hyperplasia may contribute to inflammatory response in CD.

• Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis.

  Authors: Xavier Roblin, Sylvie Pillet, Abderrahim Oussalah, Philippe Berthelot, Emilie Del Tedesco, Jean-Marc Phelip, Marie-Laure Chambonnière, Olivier Garraud, Laurent Peyrin-Biroulet, Bruno Pozzetto

  The American journal of gastroenterology. 07/2011; 106(11):2001-8.

  Previous studies have suggested an association between cytomegalovirus (CMV) infection and steroid-refractory inflammatory bowel disease. In this study, the use of CMV DNA load during acute flare-upsPrevious studies have suggested an association between cytomegalovirus (CMV) infection and steroid-refractory inflammatory bowel disease. In this study, the use of CMV DNA load during acute flare-ups of ulcerative colitis (UC) to predict resistance to immunosuppressive therapy was evaluated in intestinal tissue. Forty-two consecutive patients (sex ratio M/F: 0.9, mean age: 43.6 years) hospitalized for moderate to severe UC and treated with IV steroids were included prospectively. A colonoscopy was performed for each patient at inclusion; colonic biopsy samples of the pathological tissue, and if possible, of the healthy mucosa, were tested for histological analysis and determination of CMV DNA load by real-time polymerase chain reaction assay. Patients were treated as recommended by the current guidelines. Sixteen patients were found positive for CMV DNA in inflamed intestinal tissue but negative in endoscopically healthy tissue; all of these patients were positive for anti-CMV IgG, three exhibited CMV DNA in blood, and none was positive for intestinal CMV antigen by immunohistochemistry detection. In the 26 remaining patients, no stigmata of recent CMV infection were recorded by any technique. By multivariate analysis, the only factor associated with CMV DNA in inflammatory tissue was the resistance to steroids or to three lines of treatment (risk ratio: 4.7; 95% confidence interval: 1.2-22.5). A CMV DNA load above 250 copies/mg in tissue was predictive of resistance to three successive regimens (likelihood ratio+=4.33; area under the receiver-operating characteristic curve=0.85). Eight UC patients with CMV DNA in inflamed tissue and therapeutic failure received ganciclovir; a clinical remission was observed in seven cases, with a sustained response in five of them. The CMV DNA load determined in inflamed intestinal tissue predicts resistance to steroid treatment and to three drug regimens in UC. Initiation of an early antiviral treatment in these patients might delay the occurrence of resistance to current treatments.

• Ulcerative colitis as a sole mucosal disease: another misunderstanding?

  Authors: Joana Torres, Vincent Billioud, Laurent Peyrin-Biroulet, Jean-Frédéric Colombel

  Gut. 07/2011; 61(4):633.

• Urinary tract infections in hospitalized inflammatory bowel disease patients: A 10-year experience.

  Authors: Laurent Peyrin-Biroulet, Claire Pillot, Abderrahim Oussalah, Vincent Billioud, Nejla Aissa, Mamadou Balde, Nicolas Williet, Adeline Germain, Alain Lozniewski, Laurent Bresler, Jean-Louis Guéant, Marc-André Bigard

  Inflammatory bowel diseases. 07/2011;

  BACKGROUND: Cystitis is the most common genitourinary complication in Crohn's disease (CD). We assessed the prevalence of and risk factors for urinary tract infections (UTI) in inflammatory bowelBACKGROUND: Cystitis is the most common genitourinary complication in Crohn's disease (CD). We assessed the prevalence of and risk factors for urinary tract infections (UTI) in inflammatory bowel diseases (IBD). METHODS: Among the 1173 IBD patients of the "Nancy IBD cohort" seen between January 1, 2000 and December 31, 2009, 56 hospitalized patients had 76 documented UTI. Prevalence of UTI in IBD was calculated using rates of UTI among non-IBD patients hospitalized during the same period. The cases were compared to 175 matched IBD patients without UTI hospitalized during the same period to identify risk factors for UTI. RESULTS: Prevalence of UTI was 4% in IBD patients versus 3.3% in non-IBD patients (P = 0.1). Prevalence of UTI was 4.5% and 2.1% in ulcerative colitis (UC) and CD patients, respectively (P = 0.6). Risk factors for UTI in CD patients were perianal disease (odds ratio [OR] = 2.28, 95% confidence interval [CI], 1.06-4.89; P = 0.04) and colonic disease (OR = 2.42, 95% CI, 1.05-5.58; P = 0.04). Male gender (OR = 0.38, 95% CI, 0.17-0.85, P = 0.02) and noncomplicated behavior (OR = 0.26, 95% CI, 0.11-0.60, P = 0.002) were protective factors against UTI in CD. In UC patients, age over 40 years (OR = 9.59, 95% CI, 1.93-47.74; P = 0.006) and disease duration over 11 months (OR = 10.77, 95% CI, 1.68-68.89, P = 0.01) were risk factors for UTI. Male gender was negatively associated with UTI (OR = 0.04, 95% CI, 0.01-0.36, P = 0.00006). CONCLUSIONS: Hospitalized IBD patients are not at increased risk of UTI. Risk factors for UTI include perianal disease and colonic disease in CD and age and longer disease duration in UC. (Inflamm Bowel Dis 2011;).