Genome-wide association of IL-28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C in a Tunisian population.

BACKGROUND:   A polymorphism upstream of interleukin (IL)-28B was recently identified to be associated with a 2-fold difference in sustained virologic response (SVR) to pegylated interferon-alpha and ribavirin therapy in a large cohort of treatment-naive, adherent patients with chronic hepatitis C (CHC) virus genotype 1 (HCV-1) infection. AIM: We sought to confirm the polymorphism's clinical relevance by intention-to-treat analysis evaluating on-treatment virologic response and SVR. METHODS: We perform a prospective study in gastroenterology unitof tunis'military hospital in collaboration with immunology unit, military center of blood transfusion and laboratory of biochemistry of childrens' hospital of Tunis. HCV patients were genotyped as CC, CT or TT at the polymorphic site rs12979860 and TT, TG or GG at the polymorphic site rs8099917. Viral kinetics and rates of rapid virologic response (RVR, week 4) and SVR were compared by IL-28B type in a tunisian population. RESULTS: 154 patients including 80 healthy blood donors(sexratio: 1, mean age: 40.35 ±10.15 years) and 74 patients treated for CHC (39 men and 35 women; mean age = 51.7± 9.4 years) were enrolled. 35.6% of patients were genotyped as CC at the polymorphic site rs12979860 and 69.1% as TT at the polymorphic site rs8099917. The CC IL-28B type at rs12979860 was associated with a greater likelihood of SVR (77% vs 31.9%; p<0.001; OR: 7.11 [2.37-21.35]) compared with CT and TT. The CC IL-28B type at rs12979860 wasn't associated with improved of rapid virologic response (RVR). In a multivariate logistic regression model, the rs12979860 CC genotype predicted SVR (p<0.001; OR: 7.11 IC95% [2.37-21.35]). The TT IL-28B type at rs 8099917 wasn't associated with improved RVR and SVR compared with TG and GG. CONCLUSION: In treatment-naive HCV patients treated with pegylated interferon and ribavirin, a polymorphism upstream CC at the site rs12979860 of IL-28B is associated with increased sustained virologic response and effectively predicts treatment outcome.

Cholestatic hepatitis due to Ecballium elaterium ingestion.

Ecballium elaterium is an herbaceous plant belonging to the Cucurbitaceae family. This plant is fairly common in the Mediterranean regions. It is frequently consumed in infusion, mixture of fruit or even in aerosol in cases of fever or flu. This plant is known for its respiratory and ocular toxicity. Hepatotoxicity has never been described in the literature. We report a case of acute cholestatic hepatitis due to Ecballium elaterium in a 39 years old patient, with no past medical history.

[Endoscopic treatment of Zenker's diverticulum with soft diverticuloscope: a first Tunisian experience]. / Traitement endoscopique du diverticule de Zenker par un diverticuloscope souple: Une première expérience Tunisienne.

INTRODUCTION: Zenker's diverticulum is an acquired hernia from the posterior pharyngeal mucosa developed in the pharyngo-esophageal junction. The gold standard for diagnosis is pharyngo-esophageal barium swallow study. Open surgery with cricopharyngeal myotomy has long been the conventional treatment. Actually, endoscopic treatment is an efficient alternative to resolve the problem with shorter surgery duration and less complication. AIM: We report 3 cases of patients with Zenker's diverticulum treated with endoscopic approach in our department between 2013 and 2014. CASE REPORT: There were three men aged 71, 79 and 62 years admitted to our department with symptomatic Zenker's diverticulum. Predominant symptoms were dysphagia and regurgitation. Diverticulotomy with a flexible endoscope was performed for all patients, using argon plasma coagulation in the first case and a needle-knife in the two others. Hemostatic clips were placed at the end of the procedure. There was no complication in the last two cases. Perforation at the left lateral side of the cervical diverticulum was observed in the first patient solved by diet and antibiotics. We performed a pharyngo-esophageal barium swallow study before and after the intervention in all patients showing significant regression of the diverticulum and we observed a complete regression of clinical symptoms. CONCLUSION: Treatment with endoscopic approach using a flexible endoscope and a diverticuloscope for good exposure of the diverticulum is a safe procedure offering a rapid improvement of symptoms with a lower risk of complications and a shorter duration of hospitalization compared to surgical treatment.

Argon plasma coagulation in the management of symptomatic gastrointestinal angiodysplasia: experience in 69 consecutive patients.

BACKGROUND: Gastrointestinal angiodysplasias are associated with a high bleeding risk. AIM: to evaluate the efficiency of argon plasma electrocoagulation in the treatment of gastrointestinal angiodysplasia and to identify predictive factors of success of this technique. METHODS: Retrospective study of patients with bleeding gastrointestinal angiodysplasia treated with argon plasma electrocoagulation in the digestive endoscopy unit of the military hospital in Tunis between January 2000 and December 2011. RESULTS: 69 patients with a mean age of 68.7 years were included.The endoscopic treatment resulted in a rise in hemoglobin value from 7.3 to 9.3 g/ dl (p = 0.0001) and a decrease of transfusion requirements from 2.5 to 0.1 units of packed red cells (p <0.0001). It allowed to avoid surgery for 93.6% of patients with complex medicalhistory. Recurrence of bleeding was observed in 33.3% of patients after a mean time of 12.3 months. In a multivariate analysis, no factors were independently associated with the recurrence of bleeding. The overall survival without rebleeding at 1 and 2 years were 50% and 42% respectively. CONCLUSION: Argon plasma coagulation is an easy, effective and safe treatment of bleeding angiodysplasia. This technique is particularly interesting for patients with multiple medical problems, where surgical treatment could be burdened by significant morbidity and mortality risk.

Predictors of successful endoscopic colonic polypectomy.

BACKGROUND: Endoscopic polypectomy is the technique of choice for resection of colorectal polyps and has a major interest in the prevention of colorectal cancer. The aim of this study was to evaluate the technique, results and tolerance of colonic polypectomy. METHODS: We conducted a retrospective study including 200 consecutive patients with colorectal polyps and who underwent therapeutic endoscopic polypectomy, performed at the endoscopy unit of the Military Hospital in Tunis, between december 2008 and december 2012. RESULTS: Hundred and forty men and 60 women were included. The average age was 58.5 ± 14.5 years. The polyp was unique in more than half of cases. The most frequent location was the sigmoid colon (30.5%). Approximately, » of the polyps was larger than 10 mm. According to the Paris endoscopic classification, 78% of polyps were sessile (Is). Seventy-two percent of polyps were adenomas. Twentyfive per cent of them contained a villous component, 40 % were advanced adenomas and 3% malignant adenomas. Regarding polypectomy, 232 polyps (64%) were treated by the cold forceps, 68 polyps (18.5 %) by the diathermic snare and 63 (17.5 %) by a mucosal resection. Thirty-one percent of polypectomy were fragmented. The evaluation of the efficacy of treatment among adenomas and potentially malignant tumors, had identified 36% of treatment failure. The common independent predictive factor of fragmented resection and treatment failure were the size ≥ 10 mm (p <10-3). Among a total of 363 polypectomies, 23 (6.3%) were complicated, by 11 procedural bleeding, 11 micro-perforations and 1 delayed hemorrhage. The common independent predictive factor of these complications was the size ≥ 10 mm (p <10-3). During following, there were 12 residual polyps (6%), 36 new polyps (18%) and 6 colorectal cancers (3%). The only independent predictive factor of an unfavorable course was the multiplicity of polyps. The colorectal polyps-free survival was 90.2% at 12 months and 88.4% at 24 months. CONCLUSION: The evaluation of colorectal polypectomy in our series had confirmed the effectiveness and the low morbidity of this practice. The polyp size was the only independent predictive factor of both treatment failure and complications.

Screening for viral hepatitis C in a young Tunisian population (more than 175,000 recruits).

BACKGROUND: In front of the considerable impact of the viral hepatitis C, the prevention is more than ever a priority, based essentially on the screening. AIM: We realized an epidemiological study in a population of young recruits with the aim of considering prevalence of anti-hepatitis C Virus (anti-HCV) antibodies, describing its epidemiological evolution and establishing a cartography of the viral hepatitis C in Tunisia. METHODS: Epidemiological retrospective study of prevalence was realized from the data of the screening of anti-HCV antibodies from 2003 till 2012 of all the young recruits suggested to be incorporated for the national service or suggested to be recruited as career soldier. The study was exhaustive concerning 175 322 young and healthy male adults aged between 20 and 30 years old, originating from all parts of Tunisia. The screening was realized by third and fourth generation ELISA tests then validated by Immunoblot. RESULTS: The prevalence was 0.11% and the confirmed prevalence was 0.07%. The positive subjects were mainly between 20 and 25 years old (82.32%) and 91.05% were detected within the framework of their incorporations to the national service. The lowest prevalence was 0.07% in 2004, and the highest was 0.17% in 2011, without a significant tendency in the increase or in the decrease during the period of study (r = 0.857 ; p = 0.564). The screening of anti-VHC antibodies had an unequal geographical distribution according to a North-South decreasing gradient. The highest proportions were registered in the North-West (23.23%) and the District of Tunis (22.73%), contrary to the South-East which was weakly affected (3.54%). The governorates with the highest proportions were Tunis (19.19%), Bizerte (11.62%) and Jendouba (8.59%), the governorates of Monastir and Tataouine were weakly affected (0.51%). CONCLUSION: Prevalence of anti-HCV antibodies in the young and male Tunisian population was weak, stable without significant tendency in the increase or in the decrease from 2003 till 2012, characterized by an unequal geographical distribution according to a North-South decreasing gradient.

[Predictive factors of response to peginterferon and ribavirin in Tunisians patients with chronic hepatitis C: report of 141 cases]. / Facteurs prédictifs de réponse à la bithérapie pégylée au cours de l'hépatite chronique c dans une population tunisienne: à propos de 141 cas.

BACKGROUND: The current treatment recommendation for chronic hepatitis c is the combination of peginterferon and ribavirin. AIMS: To report our experience in the treatment of chronic hepatitis c and determine the predictive factors of sustained virologic response. METHODS: Analysis of consecutive patients treated with peginterferon and ribavirine from 1st January 2000 and 31st December 2009. results: 141 patients with an average age of 50 years were included. 75 % of the patients were infected by a VHc of genotype 1. 22.6 % of the patients were cirrhotics. 7 % of the patients (n=10) had to stop the treatment because of severe side-effects. A reduction of the dose was indicated for 16 % of the patients (n=23). Among the 117 patients with the end of treatment virologic response, 24 patients (20.5%) relapse during the 6 months after the end of therapy. The sustained virologic response in intention to treat was 66 % (57.9 % in case of genotype 1-4 and 91 % in case of genotype 2-3). In multivariate analysis, 4 independent factors of sustained virologic response were identified: the male gender, a viral genotype not 1, a pre-therapeutic viral load ≤ 600 000 UI / ml and a rapid virologic response. CONCLUSION: Approximately two thirds of the patients with chronic hepatitis c achieved a sustained virologic response with peginterferon and ribavirin. Our results are comparable to those of the literature. They will credibly be improved by the introduction of the new antiviral agents.

[Outcomes of endoscopic gluing with cyanoacrylate glue of bleeding gastric varices]. / Résultats de l'obturation endoscopique des varices gastriques hémorragiques par colle biologique.

BACKGROUND: Gastric variceal bleeding is associated with significant morbidity and mortality. Its optimal treatment is not yet standardized and glue injection is the most often proposed treatment. The longterm results of this technique are still controversial. AIM: To assess the safety and efficacy of gastric variceal glue injection. METHODS: Consecutive patients that underwent glue injection for gastric variceal bleeding in our endoscopy unit, from January 2000 to August 2011, were assessed. RESULTS: Sixteen patients (9 men, 7 women) underwent cyanoacrylate glue injections for gastric variceal bleeding. The median follow-up period of 13 patients was 33 months (three were lost to follow-up). The average age was 60 years (3 - 80 years). All patients had stigmata of recent bleeding at endoscopy. Patients underwent an average of 2 gluing sessions (1-3 sessions). N-butyl-2-cyanoacrylate (Histoacryl ®) was the most often product used. No significant complications from cyanoacrylate injection were observed. No patient had a recurrent variceal bleeding. During the median follow-up period, two patients died. CONCLUSION: Our data suggest that cyanoacrylate injection therapy is safe and effective for the prevention of short- and long-term bleeding from gastric varices.

Variceal band ligation in the prevention of variceal bleeding: a multicenter trial.

BACKGROUND/AIM: Variceal bleeding is a life-threatening complication of portal hypertension with a high probability of recurrence. Treatment to prevent first bleeding or rebleeding is mandatory. The study has been aimed at investigating the effectiveness of endoscopic band ligation in preventing upper gastrointestinal bleeding in patients with portal hypertension and to establish the clinical outcome of patients. PATIENTS AND METHODS: We analyzed in a multicenter trial, the efficacy and side effects of endoscopic band ligation for the primary and secondary prophylaxis of esophageal variceal bleeding. We assigned 603 patients with portal hypertension who were hospitalized to receive treatment with endoscopic ligation. Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The primary end point was recurrent bleeding. RESULTS: The median follow-up period was 32 months. A total of 126 patients had recurrent bleeding. All episodes were related to portal hypertension and 79 to recurrent variceal bleeding. There were major complications in 51 patients (30 had bleeding esophageal ulcers). Seventy-eight patients died, 26 deaths were related to variceal bleeding and 1 to bleeding esophageal ulcers. CONCLUSIONS: A great improvement in the prevention of variceal bleeding has emerged over the last years. However, further therapeutic options that combine higher efficacy, better tolerance and fewer side effects are needed.

Lynch syndrome in Tunisia: first description of clinical features and germline mutations.

PURPOSE: High rates of early colorectal cancers (CRC) are observed in Tunisia suggesting genetic susceptibility. Nevertheless, up to now, no molecular study has been performed in the Tunisian population. In our research, we evaluated the clinical characteristics of Tunisian families suspected of Lynch syndrome and the contribution of DNA mismatch repair (MMR) genes. METHODS: Thirty-one unrelated families suspected of Lynch syndrome were studied. Probands were tested for the presence of germline mutations in the MMR genes MLH1, MSH2, MSH6 and in MUTYH. Available tumours were analysed for microsatellite instability and expression of MMR proteins. Detailed family and medical histories were collected. RESULTS: A total of 134 cancers were noted in the 31 families, the most frequent type of cancer corresponding to CRC (69%), followed by uterine cancer (7.5%). Germline mutations were identified in 11 (35.5%) families (six MSH2, five MLH1, including seven novel mutations), seven of which fulfilled the Amsterdam criteria (sensitivity, 63.6%; positive predictive value, 58.3%). Noteworthy, germline mutations were detected in 52.6% of male patients tested, but in only 8.3% of females (p = 0.02). Moreover, CRC were essentially left sided in families without detected mutation (p = 0.017). Ages of onset of cancers and tumour spectrum were very similar in families with or without MMR germline mutation, contrasting with previous studies performed in other populations. CONCLUSIONS: MMR genes contribute significantly to CRC susceptibility in the Tunisian population. However, the cause of early CRC susceptibility remains unknown in most cases, especially in women and in patients with early left colon or rectal cancer.

[Survival in cirrhosis]. / Survie chez le Cirrhotique Tunisien.

BACKGROUND: Assessment of prognosis in patients with cirrhosis is important so as to plan their management. AIM: To determine the survival rates and to identify indicators associated with shorter life expectancy in Tunisians patients with cirrhosis. METHODS: This is a retrospective study of in-patients with cirrhosis during a 5-years period. We studied clinical and biochemical characteristics of all patients and the occurrence of decompensation or complication. The overall survival, mortality rate and causes of death were reviewed. Univariate and multivariate analysis was performed on all variables to identify parameters associated with a lower life expectancy. RESULTS: We studied 222 patients (60% females) with a mean age of 60 years. Mean follow up was 22 months. The overall survival was 52.5% at 5 years. With univariate analysis, 10 variables were associated with a poor prognosis: male gender, decompensation at admission, Child-Pugh C, esophageal varices, hypertensive gastropathy, occurrence of spontaneous bacterial peritonitis, hepatic encephalopathy, hepato-renal syndrome, hepatocellular carcinoma and portal thrombosis. With multivariate analysis, only male gender was independently correlated with survival. CONCLUSION: In our study, male gender was an uncommon parameter that predicts survival in cirrhotic patient. The Child-Pugh score was a good index for assessing the prognosis.