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Abstract Background The frequency of primary resistance to antibiotics in H. pylori isolates is increasing worldwide. In Tunisia, there are limited data regarding the pattern of H. pylori antibiotic primary resistance. Aim To evaluate the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and to detect the mutations involved in clarithromycin resistance. Materials and methods 273 strains isolated from adults and children were enrolled. The primary resistance to clarithromycin, metronidazole and amoxicillin was evaluated by means of E-test minimal inhibitory concentration (MIC). The real-time PCR using Scorpion primers was performed in all cases to assess clarithromycin primary resistance and point mutations involved. Results No resistance to amoxicillin was detected. For adults, resistance to clarithromycin and metronidazole was found respectively in 14.6% and 56.8%, and respectively in 18.8% and 25% in children. Overall, the rates of global primary resistance to clarithromycin and metronidazole in Tunisia were respectively determined in 15.4% and 51.3%. By the use of Scorpion PCR, the A2143G was the most frequent point mutation observed (88.1%), followed by the A2142G (11.9%); the A2142C was not found and 18 of 42 patients (42.8%) were infected by both the resistant and the susceptible genotype. The association of clarithromycin resistance with gender was not statistically significant, but metronidazole resistant strains were isolated more frequently in females (67.8%) than in males (32.2%) and the difference was significant. As for gastroduodenal diseases, the difference between strains isolated from patients with peptic ulceration and those with non peptic ulceration was not statistically significant. When about the distribution of resistant strains to clarithromycin and metronidazole between the three Tunisian cities (Tunis, Menzel Bourguiba and Mahdia), the difference was not statistically significant. Conclusion Local data regarding the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and the main genetic mutation involved in clarithromycin resistance in vivo (A2143G) are necessary to prove a clear need for a periodic evaluation of antibiotic consumption and new therapeutic strategies in Tunisia in order to avoid the emergence of resistant strains.

Abstract Background The immune responses to bacterial products through the pattern recognition receptor (PRR) play a pivotal role in pathogenesis of Crohn's disease. A recent study described an association between CD and some gene coding for bacterial receptor like NOD2/CARD15 gene and TLR4. In this study, we sought to determine whether TLR4 gene was associated with Crohn's disease (CD) among the Tunisian population and its correlation with clinical manifestation of the disease. Methods 90 patients with CD and 80 healthy individuals are genotyped for the Asp299Gly and Thr399Ile polymorphisms by restriction fragment length polymorphism analysis. Results The allele and genotype frequency of the TLR4 polymorphisms did not differ between patients and controls. The genotype-phenotype correlation permitted to show that the Thr399Ile polymorphism was associated with early onset disease. Conclusion this study reported the absence of association between CD and TLR4 gene in the Tunisian population, but this gene could play a role in clinical expression of the disease.

Background: The frequency of primary resistance to antibiotics in H. pylori isolates is increasing worldwide. In Tunisia, there are limited data regarding the pattern of H. pylori antibiotic primary resistance. Aim: To evaluate the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and to detect the mutations involved in clarithromycin resistance. Materials and methods: 273 strains isolated from adults and children were enrolled. The primary resistance to clarithromycin, metronidazole and amoxicillin was evaluated by means of E-test minimal inhibitory concentration (MIC). The real-time PCR using Scorpion primers was performed in all cases to assess clarithromycin primary resistance and point mutations involved. Results: No resistance to amoxicillin was detected. For adults, resistance to clarithromycin and metronidazole was found respectively in 14.6% and 56.8%, and respectively in 18.8% and 25% in children. Overall, the rates of global primary resistance to clarithromycin and metronidazole in Tunisia were respectively determined in 15.4% and 51.3%. By the use of Scorpion PCR, the A2143G was the most frequent point mutation observed (88.1%), followed by the A2142G (11.9%); the A2142C was not found and 18 of 42 patients (42.8%) were infected by both the resistant and the susceptible genotype. The association of clarithromycin resistance with gender was not statistically significant, but metronidazole resistant strains were isolated more frequently in females (67.8%) than in males (32.2%) and the difference was significant. As for gastroduodenal diseases, the difference between strains isolated from patients with peptic ulceration and those with non peptic ulceration was not statistically significant. When about the distribution of resistant strains to clarithromycin and metronidazole between the three Tunisian cities (Tunis, Menzel Bourguiba and Mahdia), the difference was not statistically significant. Conclusion: Local data regarding the primary resistance of H. pylori to clarithromycin, metronidazole and amoxicillin and the main genetic mutation involved in clarithromycin resistance in vivo (A2143G) are necessary to prove a clear need for a periodic evaluation of antibiotic consumption and new therapeutic strategies in Tunisia in order to avoid the emergence of resistant strains. [ABSTRACT FROM AUTHOR]

Background: Anti-TNFα associated to seton drainage has a central role in the treatment of complex perineal Crohn's fistulas (PAF). A precise treatment protocol is lacking., Aims: to evaluate the results of this combined treatment and identify predictive factors of response., Methods: It was a retrospective study which included all patients with complex PAF treated with Anti-TNFα., Results: We included 49 patients, mean age of 31.6 years. 17 patients had an active rectal involvement. 35 patients had azathioprin. After the induction, 43 patients had a clinical response. Maintenance therapy was started in 45 cases. After a median of 19 months of Anti-TNFα, 24 patients had a clinical remission (with radiological remission in 20), 17 a partial clinical response, and 4 were in failure. After clinico-radiologic remission setons were removed in all patients, 46% of patients who stopped Anti-TNFα treatment after clinico-radiologic remission relapsed. Absence of rectal involvement and Clinical remission after induction were the independent predictive factors of achieving a clinical remission under maintenance therapy with Anti-TNFα (p=0.016) and clinico-radiological remission (p=0.028)., Conclusion: An Anti-TNFα based treatment combined with long term loose seton drainage have contributed to the high rates of both clinical and radiological responses in this study. Obtaining a "deep" clinico-radiological remission should be the target of the treatment. Stopping the Anti-TNFα should be avoided even after obtaining such response.

Background: Thiopurines have proven efficacy in inflammatory bowel disease. However, their use is limited by adverse effects in a subset of patients., Aims: The present study aimed to evaluate toxicity profile and identify clinical predictive factors of thiopurine adverse effects in inflammatory bowel disease patients., Methods: A retrospective longitudinal study was conducted among inflammatory bowel disease patients treated with thiopurines. Multiple logistic regression was used to identify risk factors for thiopurine adverse effects., Results: A total of  210 patients were enrolled in the study. Mean age at disease onset was 29.8±11.4 years.  One hundred sixty-nine (169) patients had Crohn's disease, 29 had ulcerative colitis and 12 had indeterminate colitis. During a median follow-up of 28.5 ± 20 months, 56 patients (26.6%) had thiopurine-related adverse effects including digestive intolerance (n=14; 6.6%), immunoallergic reactions (n=8; 3.8%), myelotoxicity (n=25; 11.9%) and hepatotoxicity (n=8; 3.8%). Treatment withdrawal was reported in 19 patients (9%).  The only independent predictive factor for thiopurine adverse effects found in this study was steroid-dependence (OR= 3.96; 95% CI: 1.07- 14.53; p= 0.038)., Conclusions: Almost a quarter of inflammatory bowel disease patients treated with thiopurines developed adverse effects. These adverse effects lead to drug withdrawal in almost 9% of patients either as monotherapy or as in combination with biologic therapies.  Steroid-dependent patients were significantly at higher risk for thiopurine-related toxicity.

Background - Crohn's disease is a clinically heterogeneous condition. Our aim was to identify the phenotype evolution of Crohn's disease over time according to the Montreal Classification and to precise predictive factors of the need for immunosuppressant treatment or surgery. Methods - We included Crohn's disease patients who were followed up for at least 5 years. We excluded patients who were lost to follow up before five. Patients were classified according to the Montreal classification for phenotype at diagnosis and five years later. The evolution of phenotype over time and the need for surgery, immunosuppressive or immunomodulatory drugs were evaluated. Results - One hundred twenty consecutive patients were recruited: 70 males and 50 females. At diagnosis, 68% of patients belong to A2 as determined by the Montreal classification. Disease was most often localized in the colon. The disease location in Crohn's disease remains relatively stable over time, with 93.4% of patients showing no change in disease location. Crohn's disease phenotype changed during follow up, with an increase in stricturing and penetrating phenotypes from 6% to 11% after 5 years. The only predictive factor of phenotype change was the small bowel involvement (OR=3.7 [1.2-7.6]). During follow-up, 82% of patients have presented a severe disease as attested by the use of immunosuppressive drugs or surgery. The factors associated with the disease severity were: small bowel involvement (L1), the stricturing (B2) and penetrating (B3) phenotypes and perineal lesions (OR=17.3 [8.4-19.7]; 12 [7.6-17.2]; 3[1.7-8.3] and 2.8 [2.2-5.1] respectively), without association with age, sex or smoking habits. Conclusion - Crohn's disease evolves over time: inflammatory diseases progress to more aggressive stricturing and penetrating phenotypes. The ileal location, the stricturing and penetrating forms and perineal lesions were predictive of surgery and immunosuppressant or immunomodulatory treatment.

Introudction Crohn's disease (CD) is a lifelong condition. Multiple imaging investigations are often performed during follow-up. This could cause overexposure to radiation. The aim of our study was to determine mean radiation dose in patients  with  at least a 5-year course of CD and to determine possible risk factors associated with exposure to high doses of radiation. Methods We conducted a retrospective study including patients whose CD was diagnosed between 1998 and 2005. Epidemiologic features of patients, characteristics of the disease,  types of imaging investigations that were performed during follow-up and cumulative radiation effective dose were determined. Risk factors associated with exposure to high doses of radiation were then determined. Results One hundred sixty seven patients were included.  There were 92 males (55.1%) and 75 females (44.9%) with mean age at dianosis of 31.4±12.3years. Global radiation dose was 18.8±18.9 mSv. Twenty seven patients (16,2%) were exposed to more than  35 mSv and 4 patients (2.4%) had an exposure  of more than  75 mSv. Use of Infliximab, age at disease onset ≤ 24 years old and number of flares ≥ 8  were independent risk factors of radiation exposure more than 35 mSv with adjusted Odds ratios (OR) : 2.5 [2.1- 5.3]; 1.6 [1.2- 4.7] and 3.2 [2.1- 7.8] respectively. Similarly,  use of Infliximab and number of flares ≥ 8  were independent risk factors of radiation exposure more than 75 mSv with adjusted OR : 4.3 [2.8-9.5] and 7 [3.2-11.2] respectively. Conclusion Radiation risk seems to be increased with severe course of  CD. Both referring physicians and radiologists have the responsibility to minimise radiation exposure. Entero-magnetic resonance imaging (Entero-MRI)  may reduce this risk.

Background: Nocturnal gastroesophageal reflux has been shown to be associated with the more severe forms of gastroesophageal reflux disease (GERD), particularly with extraesophageal manifestations as well as complications of mucosal damage., Aim: To determine the frequency of nocturnal gastro esophageal reflux disease on 24-hour esophageal pH monitoring in patients with digestives or extra-digestives symptoms and to evaluate the clinical and pHmetric characteristics of nocturnal reflux in these patients., Methods: We conducted a retrospective study based on results of 24- hour esophageal pH monitoring during a 11-year period in patients with or without digestive symptoms of gastroesophageal reflux disease. The nocturnal gastroesophgeal reflux was defined., Results: We studied 696 patients (299 men, 397 women; mean age: 34.05 years). Gastroesophageal reflux was found in 350 patients (50%). Nocturnal reflux was observed in 240 patients (34.3%), mostly in association with pathological reflux in the total period (223 cases). Compared to the diurnal period, the nocturnal period was characterized by fewer number of reflux episodes (21.9±27.4 vs 67.4±5.,1 ; p<0.0001), more longer duration of reflux episodes (24.4±37.9 minutes vs 13.9± 17.5 minutes ; p<0.001), and a lower symptomatic correlation (26% vs 45% ; p=0.0005)., Conclusion: Nocturnal reflux is associated with overall reflux on the 24 hour examination. Nocturnal period is characterized by longer reflux episodes, less number of reflux episodes and less symptomatic correlation.

Background: Crohn's disease is a chronic relapsing- remitting affection. It has a strong immunologic component which represent the target of standard therapies including immunosppressants and biological therapies. However, many patients remain refracory or intolerant to these therapies., Aim: The aim of this review is to determine the effects of stem cell transplantation in patients with refractory Crohn's disease., Methods: Systematic review of observational studies, clinical trials and case reports that focused on the effectiveness and safety of stem cell transplantation in patients with refractory Crohn's disease., Results: Hematopoietic stem cell transplantation seems to be efficient in maintaining clinical and endoscopic remission in patients with Crohn's disease refractory or intolerant to current therapies. However, it has been associated to high morbidity and mortality due to chemotherapy. Mesenchymal stem cell transplantation could induce remission in patients with fistulising refractory Crohns disease with no severe side effects. Its impact on luminal Crohns disease is still controversial., Conclusion: Stem cell transplantation seems to hold promising in patients with refractory Crohn's disease. However, because of the high morbidity and mortality related to chemotherapy, hematopoietic stem cell transplantation should be used as last resort to control this disease. Effectiveness of mesenchymal stem cell transplantation in luminal Crohn's disease has yet to be proven.

Crohn's disease (CD) and ulcerative colitis (UC) are the principal inflammatory bowel diseases (IBD) which physiopathology is currently poorly elucidated. During these diseases, the participation of the epithelial cell in the installation and the perpetuation of the intestinal inflammation is now clearly implicated. In fact, the intestinal epithelium located at the interface between the internal environment and the intestinal luminal, is key to the homeostatic regulation of the intestinal barrier. This barrier can schematically be regarded as being three barriers in one: a physical, chemical and immune barrier. The barrier function of epithelial cell can be altered by various mechanisms as occurs in IBD. The goal of this article is to review the literature on the role of the epithelial cell in intestinal homeostasis and its implication in the IBD., (© 2013 médecine/sciences – Inserm.)

Background: Celiac disease (CD) is characterized by a malabsorption syndrom. The bone anomalies are one of the principal complications of this disease. The osteoporosis frequency is high: 3.4% among patients having with CD versus 0.2% in the general population., Aim: To study the bone mineral density during the CD, to compare it to a control group and to determine the anomalies of biochemical markers of bone turn over and level of interleukin 6 cytokin (IL6) in these patients., Methods: All patients with CD have a measurement of bone mineral density by dual-energy x-ray absorptiometry (DXA), a biological exam with dosing calcemia, vitamin D, parathormone (PTH), the osteoblastic bone formation markers (serum osteocalcin, ALP phosphates alkaline), bone osteoclastic activity (C Télopeptide: CTX) and of the IL6., Results: 42 patients were included, with a median age of 33.6 years. 52. 8% of the patients had a low level of D vitamine associated to a high level of PTH. An osteoporosis was noted in 21.5% of patients. No case of osteoporosis was detected in the control group. The mean level of the CTX, ostéocalcine and the IL6 was higher among patients having an osteoporosis or ostéopenia compared to patients with normal bone (p = 0,017). The factors associated with an bone loss (osteopenia or osteoporosis) were: an age > 30 years, a weight <50 kg, a level of ALP phosphates alkaline > 90 UI/ml, an hypo albuminemia < 40 g/l and a level of CTX higher than 1.2., Conclusion: Our study confirms the impact of the CD on the bone mineral statute. The relative risk to have an osteopenia or an osteoporosis was 5 in our series. The measurement of the osseous mineral density would be indicated among patients having a CD.

Background: The clinical course of inflammatory bowel disease (IBD) is characterised by a succession of relapses and remissions. A regular and a long term monitoring of such patients is required. Faecal markers, especially calprotectin's use, seem to be useful in these patients. Faecal calprotectin is a reliable maker of intestinal inflammation in IBD. Its level is assessed by a simple and a non invasive test., Aim: We proposed to review main indications and study results of faecal calprotectin test use in IBD patients., Methods: Review of literature., Results: Faecal calprotectin assessment isn't an IBD specific test. Selective use is required to have a good benefit-cost ratio. Prediction of relapses in asymptomatic patients as well as post operative reccurence seems to be the main indications for its use., Conclusion: Mucosal healing assessment after anti-TNF treatment can also be an interesting indication although it isn't well evaluated.

Background: Small-bowel videocapsule endoscopy (VCE) is a new technique in evaluation of intestinal involvement in several pathologies. Crohn's disease affects principally terminal ileum. Small bowel involvement in Crohn's disease is not well estimated by endoscopic and radiologic conventional techniques., Aims: To evaluate the performances of VCE in detection of asymptomatic proximal small bowel lesions in consecutive patients with Crohn's disease with terminal ileal involvement, to compare the results of VCE to small bowel radiography and CT-enteroclysis and to determine the therapeutic impact of VCE in these patients., Methods: A prospective study which included Crohn's disease patients with distal ileal involvement, based on radiological or endoscopic findings. We performed in all patients small bowel radiography, CT enteroclysis and VCE. Proximal involvement was characterized by presence of aphtoid, superficial or deep ulcerations in the jejunum or the proximal ileum., Results: We studied 20 patients (12 men, mean age 31.6 years). VCE confirmed the distal ileal involvement in all patients. Significative proximal lesions was observed in nine patients (jejunum only: one case, jejunum and ileum: six cases and proximal ileum: two cases), in most cases aphtoid or superficial lesions. Deep ulcerations were observed in two patients. Small bowel radiography showed proximal ileal lesions in only two patients, and CT-enteroclysis in only one patient. Treatment by azathioprine was prescribed in two patients with severe and extended small bowel lesions in VCE examination., Conclusion: VCE is more accurate than radiologic techniques in detection of small bowel lesions in Crohn's disease. In cases of severe and extended small bowel involvement, VCE can conduct to changes of therapeutic approach.

Background: Data concerning fertility during inflammatory bowel disease are insufficient and sometimes contradictory. The aims of this review are to precise the impact of inflammatory bowel disease on fertility., Methods: Literature review., Results: The risk of infertility seems to be raised at one under group of patients and made to intervene several factors of which, in particular for the Crohn's disease, the activity of the disease and the psychological impact leads by this chronic disorder. The decrease of the fertility, as very feminine as male, during the ulcerative colitis is essentially bound to the surgery. Data concerning the impact of various therapeutic used during inflammatory bowel disease on the fertility are very insufficient and interest especially male fertility.

Background: Infliximab has been an effective chimerical monoclonal antibody in Crohn's disease. Infliximab is available in Tunisia for a few years., Aims: To determine the results of the treatment of Crohn's disease by infliximab., Methods: We undertook a retrospective study relating to all the Crohn's disease patients and treated by infliximab. For all the patients, we specified the indication of the treatment, the result of the induction treatment, the recourse or not to a sequential treatment and the adverse effects of the treatment., Results: Our study related to 20 patients. It was in the majority of the cases an anoperineal and fistulizing form (15 case). Good response to the induction treatment was noted in 15 patients (75%). A sequential treatment by infliximab was undertaken among seven patients, with good results in the short and medium term. A case of death related to the treatment was noted in our series, as mortal milliary tuberculosis appeared under treatment., Conclusion: Infliximab must be reserved for particular situations of the Crohn's disease. The pre-therapeutic assessment must be complete and the monitoring of the patients must be strict, while insisting on the possibility of reactivation of latent tuberculosis in Tunisia.

Aims: To determine the frequency and the predictive factors of colectomy and restorative colo-proctectomy in patients with ulcerative colitis., Methods: We conducted an 11-year retrospective study based on hospitalized ulcerative colitis patients followed up for more than 6 months., Results: From 1995 to 2005, 115 patients were included (50 men, 65 women, mean age: 38.4 years). Mean duration of follow-up was 39.2 months (6 - 145). Colectomy was performed in 20 patients (17%), with an actuarial risk of 16% at 5 years and 35% at 10 years. Proctocolectomy with ileoanal anastomosis was performed in 16 cases and total colectomy with ileorectal anastomosis in 4 cases. In univariate analysis, factors associated with an increased risk of colectomy were pancolitic location (p = 02), acute severe colitis (p < 0.0001), treatment by intravenous corticosteroids (p < 0.0001) and intravenous cyclosporine (p = 0.001). In multivariate analysis, acute severe colitis was the only independent factor associated with colectomy (p = 0.04 OR [CI 95%] :6.66 [1.04 - 50]). In patients with distal location, the independent factor associated with colectomy was colonic extension during follow up (p = 0.04 OR [CI 95%] :7.69 [1.07 - 50]). In patients with pancolitic location, risk of colectomy was associated with acute severe colitis (p = 0.01 OR [CI 95%] :9.09 [1.58 - 50]) and years of hospitalization from 1995 to 1999 (p = 0.02 OR [CI 95%] :7.14 [1.35 - 44])., Conclusion: Although the diffusion of treatment by intravenous cyclosporin, surgery is frequently performed in our ulcerative colitis patients, specially in case of acute severe colitis. Evaluation of colonic extension during the follow-up is associated with an important prognostic impact.