E Louis

Centre Hospitalier Universitaire de Liège, Luik, Wallonia, Belgium

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Publications (194)663.72 Total impact

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    ABSTRACT: Background Crohn's disease (CD) and ulcerative colitis (UC) are potentially progressive diseases. Few data are available on the prevalence and the factors associated with mild inflammatory bowel diseases (IBD). Aim Our aim was to assess the natural history of mild CD and mild UC and to identify predictive factors of mild evolution over the long term. Methods Retrospective study of IBD patients registered in the database of the university hospital CHU of Liège, Belgium. Mild CD was defined as an inflammatory luminal disease (no stricture, abdominal or perianal fistulae) requiring no immunomodulator (IM), anti-TNF and no surgery. Mild UC was defined as no requirement for IM, anti-TNF and no colectomy. Results Four hundred and seventy-three CD and 189 UC were included (median follow-up: 13 and 11 years respectively). At 1 year, 147 patients had mild CD. At 5 years and the maximum follow-up, 56% and 13% patients still had mild CD, respectively. At 1 year, 142 patients had mild UC. At 5 years and the maximum follow-up, 72% and 44% still had a mild UC, respectively. Factors associated with long-term mild CD and UC were older age at diagnosis and absence of corticosteroids in the first year. In UC proctitis location was associated with mild UC. Conclusions In this cohort, 90% of CD patients and 3/4 of UC with mild disease at 1 year lost their mild disease status over time. An old age at diagnosis was predictive of the persistence of a mild CD and UC.
    No preview · Article · Jan 2016 · Scandinavian Journal of Gastroenterology
  • C. Reenaers · É. Louis
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    ABSTRACT: Ulcerative colitis is a chronic disease progressing to many complications. Impaired quality of life, both physically, professionally and emotionally, is present in the majority of cases. It is linked either to the inflammatory activity of the disease or to the alteration of colonic function due to tissue damage or to the consequences of coloproctectomy. Hospitalization rates are three times higher than the general population and motivated by extensive complications of the disease or investigations and treatments. The long-term consequences of histological inflammation are associated with a twofold risk of colorectal cancer. The surgery rate is 4.9%, 11.6%, 15.6% at 1, 5 and 10 years. The need for surgery is increased in the first years of the diagnosis in case of extensive colitis and if the disease was discovered at a young age. A reduction of inflammatory activity of UC by current treatments, including anti-TNF, leads to improved quality of life and a reduction in hospitalization rates. A reduction in the incidence of colorectal cancer in 5ASA has been demonstrated and, more recently, by purines through their anti-inflammatory activity. We do not currently have data on the effect of anti-TNF. The impact of treatment on surgery rates is controversial from one study to another and must be confirmed.
    No preview · Article · Oct 2015

  • No preview · Article · Sep 2015
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    ABSTRACT: Pancreatic ductal adenocarcinoma is characterized by a high rate of early metastatic relapse. Surgical resection is still recognized as the cornerstone upfront therapy. However, reported 5 years survival rates are inferior to 20-25% even when surgery is followed by chemotherapy. Margins involvement on the surgical specimen (50 to 85%) and lymph node involvement (around 70%) both strongly impact survival. Median survivals are close to those of locally advanced diseases treated by chemotherapy or chemoradiotherapy, 15 to 16 months. This review focuses on adverse prognostic factors, post-operative outcomes and their impact on multimodality therapy completion rates and survivals in patients undergoing upfront surgery. Current data and emerging results from neoadjuvant series could lead to a change in the therapeutic strategy.
    No preview · Article · Aug 2015
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    ABSTRACT: Off-line sample prefractionations applied prior to biomarker discovery proteomics are options to enable more protein identifications and detect low-abundance proteins. This work compared five commercial methods efficiency to raw serum analysis using label-free proteomics. The variability of the protein quantities determined for each process was similar to the unprefractionated serum. A 49% increase in protein identifications and 12.2% of reliable quantification were obtained. A 61 times lower limit of protein quantitation was reached compared to protein concentrations observed in raw serum. The concentrations of detected proteins were confronted to estimated reference values.
    Full-text · Article · Jul 2015 · EuPA Open Proteomics
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    ABSTRACT: Background/Purpose: Immune-mediated inflammatory disorders (IMIDs) share many genetic risk factors. Pleiotropy may exist at different levels and most of the underlying mechanisms are still to be uncovered. GWAS have identified hundreds of risk loci for IMIDs but causative genes have been identified in only a handful of cases. Recent fine-mapping efforts indicate that only a minority of risk variants are coding. This suggests that most risk variants will be regulatory hence affecting disease risk via eQTL effects. Methods: To aid in the identification of causative genes for IMIDs, we generated transcriptome information (HT12 arrays) for six blood cell types (CD4, CD8, CD19, CD14, CD15 and platelets) and intestinal biopsies at three anatomical locations (ileum, colon, rectum) for 350 healthy Caucasians. The same individuals were genotyped with SNP arrays interrogating > 700K variants, augmented by imputation from the 1KG project. To detect cis-eQTL we tested variants within 0.5 megabase windows centered on the tested probe. The nominal p-value of the best SNP within a cis-window was Sidak-corrected for the window-specific number of independent tests. The corresponding best, Sidak-corrected p-values for each probe were jointly used to estimate their respective false discovery rate.To identify likely causative genes in GWAS identified risk loci variants and also better understand pleiotropic effects, we (i) developed a method that quantifies the correlation between “disease association pattern” (DAP) and “eQTL association pattern” (EAP) and provides an empirical estimate of its significance, and (ii) evaluated the effect of fitting known risk variants as covariates in the eQTL analysis following Nica et al. (2010). We applied both approaches to celiac disease (CE) and rheumatoid arthritis (RA) and the second one to type one diabetes (T1D), multiple sclerosis (MS), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS) and psoriasis (PSO). Results: We detected > 16000 significant cis-eQTL, with a degree of sharing between cell types ranging from 38 to 90% highlighting the utility of our multi-tissue panel. GWAS variants were drivers of ciseQTL effects across the different tissues in 399 tests (23.6%), mostly in CD4 cells, and pinpointing 64 new gene-disease associations (3.7%). The number of shared loci and shared eQTL were highly correlated (rho=0.66).RA and SLE showed the highest degree of sharing. Conclusions: We identified new potential candidate genes for IMIDs and characterized pleiotropic effects through ciseQTL mapping in GWAS loci. These findings could shed a light on IMIDs pathogenesis and co-occurrence. Latest results will be presented.
    No preview · Conference Paper · May 2015
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    ABSTRACT: The therapeutic armamentarium in Crohn's disease includes mesalazine, steroids (including topical drugs), anti-metabolites (purines, methotrexate), anti-TNFα antibodies and, more recently, selective inhibitors of lymphocytes homing (vedolizumab). The efficacy of these drugs has been shown in pivotal phase 3 placebo-controlled trials and meta-analyses. However, the use of these drugs in routine practice still remains ill-defined. Those are rather the cohort studies, natural history data and therapeutic strategy trials that help the clinician to determine, for each individual patient, the treatment leading to an optimal benefit/risk profile, aiming at moving from evidence-based medicine towards personalized medicine.
    No preview · Article · May 2015 · Revue médicale de Liège

  • No preview · Article · Apr 2015 · Fundamental and Clinical Pharmacology
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    ABSTRACT: Background We aimed to investigate the 163 known loci and top SNP associated with inflammatory Bowel Disease (IBD) in a non- Caucasian Moroccan IBD cohort. Methods We genotyped 549 non- Caucasian Moroccan individuals with 285 IBD patients (211 Crohn's disease (CD), 63 Ulcerative colitis (UC) and 11 Indeterminate colitis (IC)) and 264 controls on custom designed Immunochips from ILLUMINA®. We considered the 163 loci and top SNPs associated with IBD in Caucasian individuals and negative controls matched for the minor allele frequencies (MAF). After quality controls, association analysis was done using PLINK and population stratification was corrected using the first five principal components as covariates. Simulation tests with random groups of SNP (outside the 163 loci and matched for MAF) and regions (outside the 163 IBD loci and matched for the number of independent tests) were used to test the significance of the results. Results We identified 10 regions significantly associated with IBD and UC (Table1). “Table 1: ten top SNP/loci significantly associated with IBD and UC” Surprisingly, none of NOD2 variants were found to be associated with IBD moroccan population. Increasing the sample size of the used cohort will definitively help to detect more IBD loci/SNPs associated with Moroccan IBD. Conclusion This is the first genetic study conducted in a large population of Moroccan IBD patients. Ten loci/top SNP were significantly associated with IBD and UC. Interestingly, none of the NOD2 variants were found to be associated to CD/UC and Moroccan IBD.
    Full-text · Conference Paper · Feb 2015

  • No preview · Article · Jan 2015 · Acta gastro-enterologica Belgica
  • C. Van Kemseke · E. Louis · C. Reenaers
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    ABSTRACT: Anti-TNF agents are highly effective in treating inflammatory bowel diseases, but loss of response and side-effects leading to drug interruption are often reported. New molecules are needed to treat these patients. Vedolizumab is a fully humanized anti-body inhibiting the migration of circulating lymphocytes to the gut by binding the integrin α4β7. In ulcerative colitis, clinical response, remission and mucosal healing were observed at 6 weeks in 47%, 17% and 40% of the patients, respectively. The maintenance study demonstrated 42% and 52% of clinical remission and response at week 52. In Crohn's disease, clinical response and remission were respectively observed in 15% and 31% of the patients at 6 weeks. Clinical remission at week 52 was 39%. The time to clinical response was longer in patients who had failed anti- TNF. The safety profile is excellent with the same proportion of side-effects in the placebo and in the treated groups. The most frequently reported adverse events were pharyngitis and headaches.
    No preview · Article · Jan 2015
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    ABSTRACT: Lifetime prevalence of inflammatory bowel disease (IBD) is reaching an alarming rate of >1/400 in industrialized societies. Improved understanding of disease pathogenesis is essential to develop more effective preventive, diagnostic and therapeutic measures. Genome-wide association studies (GWAS) have identified ~ 160 risk loci contributing to inherited predisposition to IBD, leading to the identification of new perturbed pathways and potential drug targets. Nevertheless, causative genes and variants remain unknown for the vast majority of risk loci. GWAS loci are likely to be regulatory and therefore alter expression levels of other genes. We hypothesize that if an IBD associated SNP is an expression quantitative loci (eQTL)-the " disease-association pattern " (DAP) should mirror the " eQTL association pattern " (EAP) of the causative gene if looking in the right target tissue(s). With this premise, our project aims to detect causative genes implicated in IBD's susceptibility through the evaluation of trans-eQTLs within GWAS loci. To this purpose, nine blood cell types and ileal, colonic and rectal biopsies have been collected for 330 healthy individuals of Northern European descent. All individuals have been genotyped with the OmniExpress Illumina array interrogating > 700K genetic variants. Transcriptome analysis has been conducted for all individuals and all cell/tissue types using Illumina HT12 arrays interrogating > 47,000 transcripts. Genotype and transcriptome data have undergone rigorous quality control. Transcriptome data have been pretreated variance stabilizing transformation, QQ normalization and correction for random and fixed effects in each cell type. Only expression probes mapped against Refseq have been considered. Genomic positions have been recovered and probes mapping to more than one genomic position (taking into account splice junctions with Tophat software) with a 96% identity have been discarded. Trans-eQTL mapping will be conducted on a SNP-by-SNP basis using linear regression (additive model) with PLINK software. In order to circumvent genome wide multiple testing penalty, we will test for a given SNP in the genome, any evidence for an excess of low p-values when testing its effect on the expression of genes located on other chromosomes or far away on the same chromosome. Confirmation of putative multigene transregulators will afterwards be performed by RNAseq experiments. We will then quantify the resemblance between DAP in the 160 GWAS-identified risk loci (raw data from IIBDGC plus imputed data) and " multigene trans-EAP " with Spearman's rank correlation. We will also evaluate the biological relevance of this list by performing a network analysis after adding the identified trans targets to the list of previously identified positional candidate genes (mapping to GWAS-identified IBD risk loci). Finally, as a the ultimate proof of causality, the selected genes will be resequenced in 3,000 IBD cases and 3,000 controls, using 600 DNA pools of 10 individuals with Illumina Truseq Amplicon. With this strategy, we expect to detect new causative variants that may constitute new drug targets for IBD. Latest results will be presented.
    Full-text · Conference Paper · Apr 2014
  • J Tack · E Louis · V Persy · D Urbain
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    ABSTRACT: Acid peptic diseases such as peptic ulcer and gastrointestinal reflux disease have a high prevalence; they can have an important impact on the patient's quality of life and generate a considerable health care cost. Proton pump inhibitors are the most potent pharmacological inhibitors of gastric acid secretion currently available and are the mainstay medical therapy for acid peptic diseases. This review provides primary care clinicians with best practice guidelines for optimal use of these drugs.
    No preview · Article · Mar 2014 · Revue médicale de Liège
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    ABSTRACT: Our goals were to assess the prevalence of biological and tissue remission in routine practice in Crohn's disease, and to evaluate the correlation between biological or tissue remission and clinical or demographic characteristics as well as their impact on disease outcome. We performed a retrospective monocenter study. Biological remission was defined by a CRP < 5 mg/I. Tissue remission was defined by the absence of ulcer at endoscopy and/or absence of signs of acute inflammation at MRI. Association with demographic, clinical and laboratory markers was studied by logistic regression models and rates of relapses, hospitalizations and surgeries were compared using the logrank test. Among the 263 patients included, 147 were in clinical remission; 102/147 (69%) were in biological remission. Fifty-six patients also had morphological evaluation: 37 (66%) were in tissue remission. Biological remission was associated with older age, higher hemoglobin and lower BMI. Tissue remission was associated with older age, lower platelets count, absence of previous surgery, and the use of immunosuppressant. Time-to-relapse was significantly longer in patients with biological remission and in patients with tissue remission as compared to patients without biological or tissue remission. Among the patients in clinical remission seen as outpatients, two thirds were either in biological and/or tissue remission. Biological and/or tissue remission was associated with a better outcome than clinical remission alone.
    No preview · Article · Mar 2014 · Acta gastro-enterologica Belgica

  • No preview · Article · Feb 2014
  • C. Pirard · E. Louis · C. Reenaers

    No preview · Article · Feb 2014 · Journal of Crohn s and Colitis

  • No preview · Article · Feb 2014 · Journal of Crohn s and Colitis
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    ABSTRACT: The thyrogastric autoimmune syndrome (TAS) was described in patients in whom the serum cross-reacted both with gastric parietal cells antigens and thyroid antigens. We report two cases illustrating the spectrum of pathological features of TAS. The first one is a case of Hashimoto's Thyroiditis associated with pernicious anemia, further developing a gastric neuroendocrine tumor during follow up. The second one is a case of Graves' disease and autoimmune reversible gastritis, secondary to Helicobacter Pylori. While type III autoimmune polyendocrinopathy (which includes TAS) is considered to be rare, this was not the case in our experience. A total of 13 % (32/240) of the patients with thyroiditis that we have prospectively followed have also autoimmune gastritis. Helicobacter pylori is clearly implicated in 16 % of the cases of autoimmune gastritis. Infection, malabsorption and gastritis are potentially reversible after bacterial eradication treatment. In the remaining 84 % of patients with gastritis, no histological or serological evidence of Helicobacter pyloriwas found. Gastric autoimmunity is then irreversible, leading to gastric severe atrophy, hypochlorhydria and hypergastrinemia. Hypergastrinemia stimulates enterochromaffin cell hyperplasia, progressing eventually to neuroendocrine tumors. We propose a diagnostic approach to improve the characterization of TAS, including a literature review and discussing some relevant animal models of infectious gastric autoimmunity. Copyright © 2014 por la Sociedad Argentina de Endocrinologia y Metabolismo.
    No preview · Article · Jan 2014
  • J Tack · E Louis · V Persy · D Urbain
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    ABSTRACT: Heartburn, reflux and epigastric pain are frequently encountered symptoms in primary care medicine. Acid peptic diseases such as peptic ulcer and gastrointestinal reflux disease have a high prevalence, can have important impact on patient quality of life and represent a considerable health care cost. Proton pump inhibitors (PPIs) are the most potent pharmacological inhibitors of gastric acid secretion currently available and are the mainstay medical therapy for acid peptic diseases. This review summarizes current evidence on treatment of acid-peptic diseases with proton pump inhibitors and provides primary care clinicians with best practice guidelines for optimal use of these drugs.
    No preview · Article · Dec 2013 · Acta gastro-enterologica Belgica
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    ABSTRACT: Background and aims In Crohn's disease, correlation between clinical assessment and disease activity at tissue level is weak. Our aim was to evaluate the value of serum calprotectin as a biomarker for Crohn's disease. Methods The STORI trial patients (n = 115) were studied at baseline, in clinical remission before infliximab withdrawal, or at the time of relapse after infliximab withdrawal. Forty healthy controls were also studied. Serum calprotectin level was measured by ELISA. Data were analyzed through correlation analyses, Kaplan Meier curves and Cox model, using available Crohn's Disease Activity Index (CDAI), Crohn's Disease Endoscopic Index of Severity (CDEIS), fecal calprotectin and C-reactive protein levels (hsCRP). Results Median serum calprotectin was 8892 ng/mL (range: 410–125,000 ng/mL) in Crohn disease patients as compared with 1318 ng/mL (range: 215.8–3770 ng/mL) in controls (P < 0.0001). Serum calprotectin was significantly higher for active disease (median = 19,584 ng/mL) than for inactive disease (median = 8353 ng/mL) (P < 0.0001). Serum calprotectin correlated with hsCRP (r = 0.4092, P < 0.0001) and CDAI (r = 0.4442, P < 0.0001), but not with CDEIS, on the contrary to fecal calprotectin (r = 0.6458, 0.5515, 0.2577 with P < 0.0001, P < 0.0001, P = 0.019 respectively). In multivariate analysis, serum calprotectin used as a discrete variable (threshold: 5675 ng/ml), appeared complementary to hsCRP (> 5 mg/l) and fecal calprotectin (> 250 μg/g) to predict relapse after infliximab withdrawal (P = 0.0173, 0.0024 and 0.0002; HR: 3.191, 3.561 and 4.120). Conclusions As a CD biomarker, serum calprotectin has a similar profile as hsCRP. It is also complementary to fecal calprotectin and hsCRP for prediction of relapse after infliximab withdrawal.
    No preview · Article · Dec 2013 · Journal of Crohn s and Colitis

Publication Stats

3k Citations
663.72 Total Impact Points

Institutions

  • 1994-2015
    • Centre Hospitalier Universitaire de Liège
      • Department of Pathology
      Luik, Wallonia, Belgium
  • 1998-2013
    • University of Liège
      • • Department of Gastroenterology
      • • Department of Pathology
      • • Department of Pneumology
      Luik, Walloon, Belgium
    • University of Leuven
      Louvain, Flemish, Belgium
  • 2005
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2004-2005
    • Free University of Brussels
      • Department of Gastroenterology
      Bruxelles, Brussels Capital Region, Belgium
  • 1998-1999
    • University of Southampton
      Southampton, England, United Kingdom
  • 1995
    • Province de Liège
      Luik, Wallonia, Belgium