Marc Ferrante

Universitair Ziekenhuis Leuven, Louvain, Flanders, Belgium

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Publications (180)1600.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Patients with inflammatory bowel disease (IBD) have a higher risk of developing thromboembolic events (TE) compared with the healthy population. Aim: This study aimed to describe a cohort of IBD patients with a history of TE focusing on recurrence of TE, disease activity and IBD medication at the time of TE and surgery before TE. Materials and methods: In a retrospective monocentric cohort study, we included IBD patients in whom an arterial and/or venous TE occurred. Results: Eighty-four IBD patients with a history of TE (63% Crohn's disease, 44% men) and a mean age of 45±15 years were included; 25/84 patients (30%) were identified to have recurrent TE. Seventy out of 84 (83%) developed a venous TE, with a deep vein thrombosis as the major manifestation (28/70, 40%), followed by a pulmonary embolism (16/70, 23%). At the time of TE, 60/84 (71%) patients were diagnosed with active disease. In all, 23% patients were on 5-aminosalicylic acids, 36% on steroids, 18% on azathioprine, 5% on methotrexate, 12% on biologicals and 23% were not receiving specific IBD treatment. Moreover, within a 6-month period preceding the TE, 28/84 (33%) patients underwent surgery, of whom 17% received thromboprophylaxis at hospital discharge. Conclusion: We confirm the association between disease activity and the occurrence of TE. A substantial number of patients had additional risk factors such as recurrence of TE. In all, 36% received steroids at the time of TE and 33% underwent recent surgery, of whom only a minority received thromboprophylaxis at hospital discharge. Further efforts are required to increase thromboprophylaxis in at-risk patients.
    European journal of gastroenterology & hepatology 10/2015; DOI:10.1097/MEG.0000000000000495 · 2.25 Impact Factor
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    ABSTRACT: Background and aims: Fecal microbiota transplantation is a successful therapy for patients with refractory Clostridium difficile infections. It has also been suggested as a treatment option for inflammatory bowel disease, given the role of the intestinal microbiota in this disease. We assessed the impact of fecal microbiota transplantation in patients with inflammatory bowel disease and studied predictors of clinical (non)response in microbial profiles of donors and patients. Methods: Fourteen refractory patients (8 ulcerative colitis and 6 Crohn's disease) underwent ileocolonoscopy with fecal microbiota transplantation through naso-jejunal (n=9) or rectal tube (n=5). Efficacy was assessed by endoscopic healing at week 8, clinical activity scores and C-reactive protein measurement. Fecal microbiota was analyzed by 16S rDNA pyrosequencing. Results: There was no significant improvement among the 6 patients with Crohn's disease at week 8 following fecal microbiota transplantation. One patient experienced temporary clinical remission for 6 weeks. In contrast, 2/8 patients with ulcerative colitis had endoscopic remission at week 8 and of the 6 remaining patients with ulcerative colitis, one reported temporary remission for 6 weeks. The donor microbiota richness and the number of transferred phylotypes were associated with treatment success. Persistent increased C-reactive protein two weeks after transplantation was predictive for failure of response. Conclusion: Fecal microbiota transplantation led to endoscopic and long-term (> 2 years) remission in 2 out of 8 ulcerative colitis patients. Higher donor richness was associated with successful transplant. Therefore, fecal microbiota transplantation with donor pre-screening could be a treatment option for selected refractory ulcerative colitis patients.
    Journal of Crohn s and Colitis 10/2015; DOI:10.1093/ecco-jcc/jjv203 · 6.23 Impact Factor
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    ABSTRACT: Objective: Pouchitis is the most common complication after colectomy with ileal pouch-anal anastomosis (IPAA) for UC and the risk is the highest within the 1st year after surgery. The pathogenesis is not completely understood but clinical response to antibiotics suggests a role for gut microbiota. We hypothesised that the risk for pouchitis can be predicted based on the faecal microbial composition before colectomy. Design: Faecal samples from 21 patients with UC undergoing IPAA were prospectively collected before colectomy and at predefined clinical visits at 1 month, 3 months, 6 months and 12 months after IPAA. The predominant microbiota was analysed using community profiling with denaturing gradient gel electrophoresis followed by quantitative real-time PCR validation. Results: Cluster analysis before colectomy distinguished patients with pouchitis from those with normal pouch during the 1st year of follow-up. In patients developing pouchitis, an increase of Ruminococcus gnavus (p<0.001), Bacteroides vulgatus (p=0.043), Clostridium perfringens (p=0.011) and a reduction of two Lachnospiraceae genera (Blautia (p=0.04), Roseburia (p=0.008)) was observed. A score combining these five bacterial risk factors was calculated and presence of at least two risk factors showed a sensitivity and specificity of 100% and 63.6%, respectively. Conclusions: Presence of R. gnavus, B. vulgatus and C. perfringens and absence of Blautia and Roseburia in faecal samples of patients with UC before surgery is associated with a higher risk of pouchitis after IPAA. Our findings suggest new predictive and therapeutic strategies in patients undergoing colectomy with IPAA.
    Gut 10/2015; DOI:10.1136/gutjnl-2015-309398 · 14.66 Impact Factor

  • Journal de Chirurgie Viscerale 10/2015; 152(5):A15. DOI:10.1016/S1878-786X(15)30029-2
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    ABSTRACT: Background The detrimental effect of smoking on development and progression of Crohn's disease (CD) is generally accepted.AimWe evaluated the awareness of smoking risks in the Belgian inflammatory bowel disease (IBD) population.Methods In the out-patient clinic of a tertiary referral centre, 625 consecutive patients with CD, 238 patients with ulcerative colitis (UC) and 289 non-IBD controls, filled out a simple questionnaire. This questionnaire included data on smoking behaviour and awareness of smoking-related health effects, including effects on IBD.ResultsAt diagnosis, more CD patients were active smokers compared to UC (40% vs. 17%, P < 0.001). Remarkably, smoking cessation rates after diagnosis were similar for CD and UC (both 56%, P = 0.997). The great majority recognised a detrimental influence of smoking on general health (98–99%), lung cancer (95–97%), myocardial infarction (89–92%) and stroke (78–87%). Although CD patients more frequently acknowledged risks of smoking on their disease, only 37% were aware of a link with CD development, 30% of increased surgical rates and 27% of increased post-operative CD recurrence. Active smokers more frequently denied an increased risk of surgery and higher post-operative CD recurrence. Intriguingly, within the active smokers with CD, those not willing to quit smoking most often denied a potential bad influence of smoking. Taking into account disease duration, previous surgery, education level, working status and nicotine dependence, we were unable to define specific subgroups of patients requiring extra education.Conclusion Although patients with Crohn's disease were better informed on the detrimental effects of smoking, the awareness rate was still low.
    Alimentary Pharmacology & Therapeutics 10/2015; 42(11):n/a-n/a. DOI:10.1111/apt.13423 · 5.73 Impact Factor
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    ABSTRACT: Background: Anti-tumor necrosis factor (TNF) therapy has become a standard therapy for severe inflammatory bowel diseases (IBD), but its effect on B lymphocytes is largely unexplored. In this study we investigated peripheral blood B cells, B-cell subsets, and CD40 expression in patients with IBD before and during anti-TNF therapy with infliximab (IFX). Methods: Blood was taken from healthy controls (n = 52) and patients with active IBD before (n = 46) and/or during anti-TNF therapy (n = 55). B-cell markers were detected by immunofluorescent staining and FACS analysis. Patients were classified as responders or nonresponders to anti-TNF therapy. Results: We found a numerical deficiency of circulating CD19 B cells, a lower activation state (CD40 expression) and lower proportions of CD5 B cells and IgMIgDCD27 preswitched memory cells among B cells in active patients with IBD before IFX therapy compared with healthy controls. IFX treatment increased CD19 B-cell numbers as well as the proportions of named B-cell subsets in responders but not in nonresponders. IFX more effectively upregulated CD40 expression in responders than in nonresponders. Restoration of B cells correlated with the biological response to therapy (C-reactive protein). Trough serum levels of IFX correlated with the number of B cells during therapy. Conclusions: A lower number of circulating B cells, a low CD40 expression, and a decrease in the proportion of CD5 and in the preswitched memory subset characterize active IBD. Restoration of these abnormalities correlates with the clinical response to anti-TNF therapy. The mechanism for this effect on B cells should be further explored.
    Inflammatory Bowel Diseases 09/2015; 21(12). DOI:10.1097/MIB.0000000000000554 · 4.46 Impact Factor
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    ABSTRACT: Background and aims: Surgery for Crohn's disease (CD) can be complicated by an enhanced inflammatory response. This retrospective study aims to compare the inflammatory response measured by C-reactive protein (CRP) in patients operated for CD with patients undergoing similar surgery for colorectal cancer (CRC). Methods: All CD patients undergoing an ileocaecal resection between February 2001 and December 2013 were retrieved from a prospectively maintained database. The same number of patients with a CRC of the ascending colon, undergoing a laparoscopic right hemicolectomy between March 2009 and June 2014, were retrieved from a CRC database. CRP level during the first 7 postoperative days was used as primary outcome. Results: 112 consecutive CD patients (male 40.2%; median age: 32.3 yrs; interquartile range, IQR: 25.2 - 45.1) and 112 consecutive CRC patients (male 53.6%, median age 71.6 yrs; IQR: 64.7 - 77.5) were included. Postoperative CRP level in the CD group was on average 27% higher compared to the CRC group (p=0.02). The day-specific differences in CRP values were 21% (p = 0.021, 95% CI: 3% - 41%), 41% (p = 0.005, 95% CI: 11% - 79%), 49% (p = 0.007, 95% CI: 11% - 96%) and 49% (p = 0.006, 95% CI: 12% - 100%) higher for CD patients at day 1, 4, 5 and 6 respectively. The difference in postoperative CRP level was partially due to differences in preoperative CRP level.ConclusionCD patients develop a higher postoperative CRP level, probably reflecting an enhanced postoperative inflammatory response, which may be triggered by a higher preoperative inflammatory state.
    Journal of Crohn s and Colitis 09/2015; DOI:10.1093/ecco-jcc/jjv161 · 6.23 Impact Factor
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    ABSTRACT: Background & aims: Prediction of primary non-response (PNR) to anti-TNFs in inflammatory bowel disease (IBD) is direly needed to select the most optimal therapeutic class for a given patient. We developed a matrix-based prediction tool to predict response to infliximab (IFX) in Crohn's disease (CD) patients. Methods: This retrospective single-center study included 201 anti-TNF naïve CD patients who started with IFX induction therapy. PNR occurred in 16 (8%) patients. Clinical, biological (including serum TNF and the IBD serology 6 panel (Prometheus Laboratories)) and genetic (the 163 validated IBD risk loci) markers were collected prior to start. Based on the best fitted regression model, probabilities of primary response to IFX were calculated and arranged in a prediction matrix tool. Results: Multiple logistic regression withheld three final independent predictors (P<0.05) for PNR: age at first IFX, (OR [95% CI] of 1.1 [1.0-1.1]), BMI (0.86 [0.7-1.0]) and prior surgery (4.4 [1.2-16.5]). The accuracy of this prediction model did not improve when the genetic markers were added (AUC from 0.80 [0.67-0.93] to 0.78 [0.65-0.91]). The predicted probabilities for PNR to IFX increased from 1% to 53% depending on the combination of final predictors. Conclusions: Readily available clinical factors (age at first IFX, BMI and prior surgery) outperform serologic and IBD risk loci in prediction of primary response to infliximab in this real-life cohort of CD patients. This matrix tool could be useful for guiding physicians and may avoid unnecessary or inappropriate exposure to IFX in IBD patients unlikely to benefit.
    Journal of Crohn s and Colitis 09/2015; DOI:10.1093/ecco-jcc/jjv156 · 6.23 Impact Factor
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    ABSTRACT: A defect in regulatory T cells (Tregs) may be involved in the pathogenesis of inflammatory bowel diseases (IBD). Several subsets of human Foxp3 Tregs (activated and resting Tregs) have now been identified, as well as an IL-10 and IFN-γ double producing Foxp3 type 1 regulatory-like T cell (Tr1L). We have quantified these Tregs in patients with active IBD and during therapy with infliximab (IFX). Blood samples were obtained from healthy controls (n = 54) and patients with active IBD, either before (n = 62) or during IFX therapy (n = 75). Tregs were identified by immunofluorescent staining and flow cytometry analysis. Resting and activated Foxp3 Tregs can be differentiated from Foxp3effector T cells (Foxp3 Teff) by the expression of CD45RA. Tr1L are identified as CD4CD45RACD25CD127Foxp3 T cells. A numerical deficiency of circulating resting Tregs, activated Treg cells, and Tr1L was documented in patients with active IBD. Baseline levels of these Treg subsets predicted clinical responses to IFX. We documented an upregulation of all 3 subsets during IFX therapy. Moreover, after therapy, significant differences in Treg subsets were seen between responders and nonresponders to IFX. Restoration of Tregs correlated with the clinical and biological response to IFX therapy. Trough serum levels of IFX positively correlated with the proportion of activated Treg cells and Tr1L during therapy. IFX therapy, when successful, results in upmodulation of the different types of Treg cells in the blood of patients with IBD. This effect might be relevant for understanding the mechanism of action of anti-TNF agents.
    Inflammatory Bowel Diseases 08/2015; 21(10). DOI:10.1097/MIB.0000000000000509 · 4.46 Impact Factor
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    ABSTRACT: Background: The occurrence of thromboembolic events (TE) is an important extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The aim of this study was to compare fibrinolysis and clot lysis parameters between (1) patients with IBD and healthy controls and (2) patients with IBD with TE (IBD + TE) and without TE (IBD − TE). Methods: One hundred thirteen healthy controls and 202 patients with IBD, of which 84 patients with IBD + TE and 118 patients with IBD − TE, were included in this case–control study. Three clot lysis parameters (area under the curve, 50% clot lysis time, and amplitude) were determined using a clot lysis assay. Plasminogen activator inhibitor 1 (PAI-1) and thrombin activatable fibrinolysis inhibitor concentrations were determined by enzyme-linked immunosorbent assay. Results: PAI-1 antigen, active PAI-1, and intact thrombin activatable fibrinolysis inhibitor concentrations, as well as 50% clot lysis time and area under the curve, were significantly associated with the presence of IBD (all P < 0.05). The median time between TE and plasma collection was 5.0 (1.8–11.0) years. Comparing IBD + TE versus IBD − TE, active to total PAI-1 ratio (0.36 [0.24–0.61] versus 0.24 [0.13–0.40]), area under the curve (31 [24–49] versus 22 [13-31]), 50% clot lysis time (110 [64–132] versus 95 [70–126] minutes), and amplitude (0.295 [0.222–0.436] versus 0.241 [0.168–0.308]) were significantly higher in IBD + TE (all P <0.05) and remained higher after adjustment for age, gender, C-reactive protein, type of disease, presence of comorbidities, and disease activity. Conclusions: Patients with IBD have an altered clot lysis profile compared with healthy controls. Clot lysis parameters differ significantly between patients with IBD with and without a history of TE and should be included in the risk assessment.
    Inflammatory Bowel Diseases 08/2015; 21(11). DOI:10.1097/MIB.0000000000000531 · 4.46 Impact Factor

  • Acta gastro-enterologica Belgica 06/2015; 78(1):26-9. · 0.91 Impact Factor

  • Digestive Disease Week; 05/2015
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    ABSTRACT: Prophylactic azathioprine (AZA) is efficacious in preventing postoperative Crohn's disease (CD) recurrence. However, it is unknown if AZA should be started immediately after surgery. We compared efficacy of systematic versus endoscopy-driven AZA in preventing CD recurrence at week 102. CD patients undergoing curative resection with ileocolonic anastomosis and at higher risk of recurrence were included in this prospective, multicenter trial. Patients were randomized to systematic AZA initiated ≤2 weeks from surgery, or endoscopy-driven AZA where therapy was only initiated in case of endoscopic recurrence (Rutgeerts' score ≥i2) at weeks 26 or 52 following surgery. The primary endpoint was endoscopic remission (i0-i1) at week 102. Secondary endpoints included complete endoscopic remission (i0), and clinical remission. The study was prematurely stopped due to slow recruitment. Between 2005 and 2011, 63 patients (28 male, median age 36 years) were randomized to systematic (n=32) or endoscopy-driven AZA (n=31). Twenty-one patients withdrew prematurely (8 clinical recurrence, 6 adverse reactions to AZA, 7 patient's preference). In the endoscopy-driven AZA group, 14 patients had to initiate AZA (11 at week 26, 3 at week 52). Endoscopic remission was achieved by 50% in the systematic and 42% in the endoscopy-driven AZA group (p=0.521). No difference in secondary endpoints could be determined. Systematic AZA therapy in patients at higher risk of postoperative CD recurrence is not superior to endoscopy-driven treatment. Early postoperative endoscopic evaluation between week 26-52 seems most appropriate to guide further therapy, but larger studies are warranted. (, Number NCT02247258). Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email:
    Journal of Crohn s and Colitis 04/2015; 8(8). DOI:10.1093/ecco-jcc/jjv076 · 6.23 Impact Factor
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    ABSTRACT: Dear Editor, We read with great interest the manuscript by Ungar and colleagues describing the temporal evolution of antibodies to infliximab (ATI) in patients with IBD treated with infliximab (IFX).1 By prospectively following 125 patients with IBD, they showed that ATI formation is a dynamic process. Clinically relevant ATI were typically formed within the first 12 months but transient ATI, which are of little clinical significance, can be formed at any time during treatment. They furthermore demonstrated that the evolution of ATI correlates with clinical loss of response and that concomitant immunomodulator use prolonged ATI-free survival, which is in line with previous reports. Nevertheless, patient-related factors possibly influencing ATI formation weren't considered and haven't been studied extensively. We hypothesised that ATI formation may be triggered by HLA-DRB1 alleles, as was shown for immunogenicity to interferon-β therapy in multiple sclerosis.2 We retrospectively analysed 192 patients with IBD: 76 patients developed ATI during IFX maintenance treatment (=ATI+) (44 Crohn's disease (CD), 32 UC) and these were matched with 116 patients (64 CD, 52 UC) who never developed ATI (=ATI−). All patients were antitumour necrosis factor naïve before IFX … [Full text of this article]
    Gut 04/2015; 64(8). DOI:10.1136/gutjnl-2015-309698 · 14.66 Impact Factor
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    ABSTRACT: Data on immunogenicity to adalimumab (ADL) therapy in patients with IBD is limited. We performed additional analyses on the Karmiris cohort using the homogeneous mobility shift assay (HMSA) focusing on the inter-relationship of serum ADL concentration, antibodies-to-adalimumab (ATA), inflammatory markers and sustained response. 536 prospectively collected serum samples were available for analysis of ADL concentration and ATA using HMSA. We studied the role of week 4 serum ADL concentration and immunomodulator (IMM) use on ATA formation with a Cox proportional hazards model. Mixed model repeated measures analysis was performed to assess the independent effects of serum ADL concentration and ATA on C-reactive protein (CRP) and response. ATA was detected in 20% of patients after a median of 34 (12.4-60.5) weeks. ATA-positive samples correlated with lower serum ADL concentration (p<0.001). Cox regression modelling showed that week 4 ADL concentration of <5 µg/mL significantly increased the future risk of ATA formation (HR=25.1; 95% CI 5.6 to 111.9; p=0.0002) and that IMM co-treatment prevented ATA formation (HR=0.23; 95% CI 0.06 to 0.86; p=0.0293). Regression modelling showed a negative correlation between CRP and ADL concentration (p=0.0001) and a positive one with ATA (p=0.0186). The model revealed that both lower serum ADL concentration and ATA were independently associated with future CRP (p=0.0213 and p=0.0013 respectively). ATA positivity was associated with discontinuation of ADL because of loss or response (OR=3.04; 95% CI 1.039 to 9.093; p=0.034). ATA were detected in 20% of patients. Risk of ATA formation increased with lower early serum ADL concentration and in patients not on IMM. ATA and ADL were strongly associated with higher future CRP level and discontinuation of ADL. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Gut 04/2015; DOI:10.1136/gutjnl-2014-307882 · 14.66 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-703-S-704. DOI:10.1016/S0016-5085(15)32386-6 · 16.72 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-108. DOI:10.1016/S0016-5085(15)30371-1 · 16.72 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-240. DOI:10.1016/S0016-5085(15)30789-7 · 16.72 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-62. DOI:10.1016/S0016-5085(15)30215-8 · 16.72 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-864. DOI:10.1016/S0016-5085(15)32930-9 · 16.72 Impact Factor

Publication Stats

3k Citations
1,600.24 Total Impact Points


  • 2004-2015
    • Universitair Ziekenhuis Leuven
      • Department of Gastroenterology
      Louvain, Flanders, Belgium
  • 2014
    • The University of Edinburgh
      • Institute of Immunology and Infection Research
      Edinburgh, Scotland, United Kingdom
    • Tel Aviv Sourasky Medical Center
      Tell Afif, Tel Aviv, Israel
  • 2013
    • Oxford University Hospitals NHS Trust
      Oxford, England, United Kingdom
  • 2006-2013
    • Universitair Ziekenhuis Ghent
      Gand, Flanders, Belgium
  • 2004-2013
    • University of Leuven
      • Translational Research Center for Gastrointestinal Disorders (TARGID)
      Louvain, Flemish, Belgium
  • 2012
    • McGill University Health Centre
      Montréal, Quebec, Canada
    • Nagasaki University
      • Department of Pathology
      Nagasaki, Nagasaki, Japan
  • 2008
    • University of Pennsylvania
      • Department of Medicine
      Filadelfia, Pennsylvania, United States
  • 2005
    • The Catholic University of America
      Washington, Washington, D.C., United States