Tunisian consensus on the management of Helicobacter Pylori infection.

Helicobacter pylori infection is the most common infectious disease worldwide. It is associated with duodenal and gastric ulcer disease and the risk of gastric neoplasia. The management of helicobacter pylori infection currently represents a real challenge for clinicians, given the ever-increasing rate of resistance of Helicobacter pyolori to various antibiotics. In this consensus document, we present recommendations adapted to the Tunisian context, including indications for the detection of helicobacter pylori infection, indications for the use of different diagnostic methods, and a therapeutic strategy for the management of Helicobacter pylori infection.

Toxicity profile of thiopurines in inflammatory bowel disease: a retrospective cohort analysis.

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.

Complex perianal fistulas in Crohn's disease: An anti-TNF α based medico-surgical treatment with magnetic imaging assessment.

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.

Radiation exposure in Crohn's disease patients.

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.

Changes of Crohn's disease phenotype over time.

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.

Stem cell transplantation as rescue therapy for refractory Crohn's disease: a sytematic review.

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.

[Epithelial cell in intestinal homeostasis and inflammatory bowel diseases]. / Rôle de la cellule épithéliale dans l'homéostasie intestinale et les maladies inflammatoires chroniques de l'intestin.

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.

[Is there any interest to dose the azathioprine's metabolites during inflammatory bowel diseases?]. / Y a-t-il intérêt à doser les métabolites de l'azathioprine chez les malades ayant une maladie inflammatoire chronique de l'intestin ?

OBJECTIVE: The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population. METHOD: We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1 year. Each patient had a dosage of azathioprine metabolites. RESULTS: We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients. CONCLUSION: Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule.

[Bone metabolism, biochemical markers of bone resorption and formation processes and interleukine 6 cytokin level during coeliac disease]. / Anomalies du métabolisme osseux et résultats des marqueurs biochimiques du remodelage osseux et de l'interleukine 6 au cours de la maladie coeliaque.

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.

[Is APRI score a suitable tool for prediction of fibrosis in Tunisian patients with genotype 1 chronic viral hepatitis C?]. / Le score April est il fiable pour la prediction de la fibrose chez les patients Tunisiens atteints d'hepatite chronique virale C de genotype 1?

BACKGROUND: Therapeutic indications in chronic genotype 1 hepatitis C are based on severity of fibrosis. APRI score is a simple, cheap and reproducible biochemical test. Performances of APRI score in Tunisian population with chronic hepatitis C were not previously prospectively studied. AIM: To evaluate the performances of APRI score in prediction of severity of fibrosis in chronic genotype 1 hepatitis C based on a prospective study. METHODS: We prospectively include patients with chronic genotype 1 hepatitis C and positive viral load. Hepatic biopsy was performed in all included patients and abnormalities were classified according to METAVIR classification. In all patients, APRI score was calculated based on biochemical data collected within the 15 days before hepatic biopsy. RESULTS: We studied 140 patients (46 men, mean age 48.4 years (20 - 65 years)). Mean APRI score was 0.89 (0.18 - 3.72). Statistically significant correlation was observed between APRI score and fibrosis severity (r = 0.31 p < 0.0001). APRI score was higher in patients with severe fibrosis (F2, F3 or F4) compared to patients with moderate fibrosis (F0 or F1) (0.97 + 0.68 vs 0.62 + 0.44; p 0.009). Threshold value of APRI score of 0.72 was associated with area under the curve of 0.65 + 0.05 (0.57 - 0.73), sensitivity of 56.3% and specificity of 75.8% in prediction of severe fibrosis. APRI score was also higher in patients with cirrhosis (1.24 + 0.79 vs 0.85 + 0.61; p = 0.01). Threshold value of 0.86 was associated with area under the curve of 0.69 + 0.07 (0.61 - 0.77), sensitivity of 76.4% and specificity of 65.8% in prediction of cirrhosis. CONCLUSION: APRI score is not a good alternative to hepatic biopsy although a strong correlation with fibrosis severity, because of relatively low area under the curve, sensitivity and specificity in prediction of severe fibrosis and cirrhosis.

[Long-term functional outcome of laparoscopic anti-reflux surgery]. / Résultats fonctionnels à long terme de la chirurgie anti-reflux sous coelioscopie.

BACKGROUND: Medical treatment of gastro esophageal reflux is associated with relapse in 30% of cases. In these patients, the best therapeutic option is surgical treatment, performed laparoscopically.However, there are few data on long-term functional outcome. AIM: To determine long-term results of laparoscopic antireflux surgery the mechanisms involved in patients with worse results. METHODS: We studied patients operated for reflux disease. They had either total or partial laparoscopic fundoplication. These patients were contacted to assess postoperative improvement, satisfaction and asked about the occurrence or not of a persistent postoperative dysphagia. RESULTS: Seventy one patients were included (Nissen in 61% of the cases and Toupet in 39%). After an average period of 52.4 months,80 % of patients were satisfied. 58% were completely improved,while 31% were partially improved after surgery. Persistent reflux symptoms reflux were observed in 8 patients and postoperative dysphagia was reported by 11 patients. Gastroesophageal reflux revealed by chronic cough was the only independent parameter associated with bad functional results in our patients. CONCLUSION: Laparoscopic anti reflux surgery is associated with a high frequency of satisfaction. However, patients with chronic cough respond less better to surgery. Strict selection of the patients before surgery must be done, to improve the functional results after anti reflux surgery.