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Background/Aim: To investigate the possible association between the polymorphism of the CTLA-4 exon 1 +49 A/G and susceptibility to Crohn′s disease (CD) and ulcerative colitis (UC) in the Tunisian population. Methods: The +49 A/G dimorphism was analyzed in 119 patients with CD, 65 patients with UC, and 100 controls by the polymerase chain reaction-restriction fragment length polymorphism method. Results: Significantly higher frequencies of the CTLA-4 +49A allele and A/A homozygous individuals were observed in patients with CD when compared with controls (pc = 0.0023 and pc = 0.0003, respectively). Analysis of CTLA-4 A/G polymorphism with respect to sex in CD showed a significant difference in A/A genotypes between female patients and controls (pc = 0.0001 and pc = 0.038, respectively). There were no differences in the subgroups of patients with CD. Conclusions: Forty-nine A alleles and AA genotype are associated with CD susceptibility in Tunisians. Other genes involved in the T-cell regulation remain strong candidates for IBD susceptibility and require further investigation.

Aim: Interleukin (IL)-18 can regulate the Th2-mediated immune response and it may be involved in the pathogenesis of Th1 and Th2 chronic inflammatory diseases. This study sought to detect a possible association between two single nucleotide polymorphisms (SNPs) (-137G/C and -607C/A) in the IL-18 gene promoter region and susceptibility to inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) in the Tunisian population. Methods: The (-137G/C and -607C/A) IL-18 polymorphism was analyzed in 105 patients with CD, 59 patients with UC, and 100 controls using the sequence-specific polymerase chain reaction method. Results: The distribution of allele and genotype frequencies illustrate that the -137G/G genotype frequency was significantly higher in UC than in controls (p value corrected (pc) = 0.038). On the other hand, we found a statistically significant association (pc = 0.033) between genotype AA of the IL-18 gene promoter (-607C/A) polymorphism in UC patients and the distal localization of the lesions. In CD, no significant differences were observed at positions -607 and -137. The analysis of IBD patients according to clinical behavior revealed no difference. Conclusion: The two SNPs at position -607 (C/A) and -137 (G/C) in the promoter region of the IL-18 gene was associated with the development of UC but not CD, providing a strong support for an IBD susceptibility gene in the region surrounding IL-18. It remains to be determined precisely how the IL-18 alleles influence the pathogenesis of IBD. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The present study was undertaken to investigate the association between Hepatitis B Virus (HBV) infection and polymorphisms of tumour necrosis factor alpha TNF-α − 308 G > A, TNF-α − 238 G > A and TNF RII VNTR (p75) gene promoter in a Tunisian population. Blood samples were collected from 100 Tunisian patients with HBV infection, 45 with Chronic Hepatitis (CH), 36 with Liver Cirrhosis (LC), 15 with Hepatocellular Carcinoma (HCC) and 200 healthy individuals of similar ethnicity. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping of the analysed polymorphisms was performed using Amplified Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR), Restriction Fragment Length Polymorphism (RFLP) and Variable Number Tandem Repeat PCR (PCR-VNTR). The variant homozygotes − 308 GG were associated with 50% decreased risk of HBV chronic infection (GG vs AA + GA; p = 0.010; OR = 0.50; 95%CI = 0.29–0.85). However, the carriers of minor allele − 308 A have higher risk (1.5 times) to develop a chronic infection than other patients ( p = 0.027; OR = 1.46; 95%CI = 1.04–2.06). The minor allele of − 238 polymorphism was positively associated with virus resistance and the development of chronic infection ( p = 0.043; OR = 1.42; 95%CI = 1.01 1.99). The distribution of − 308, − 238 and TNF RII VNTR (p75) among the three groups differed significantly. For HCC groups, there were statistically significant differences in allele distribution in − 308, − 238 respectively in which A allele remains a risk factor for HBV evolution to HCC ( p = 0.008 and p = 0.026). Haplotype analysis revealed that TNF-α (− 308A; − 238A) was significantly associated to HBV chronic infection and moreover to disease aggravation to HCC stage. Our findings imply that variations in the genes governing the levels of constitutive and inducible TNF-α and TNF RII might be an important risk factor, which could explain the variable outcomes of HBV infection. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D plays a role in regulating the immune response through an immunomodulatory effect, and is probably involved in the pathophysiology of Crohn's disease (CD)., Aim: to assess vitamin D status in patients with CD as well as in healthy controls and to determine associated factors of vitamin D deficiency in patients with CD., Methods: We conducted a prospective study over 18 months, including CD patients with age and sex matched with healthy controls. Suboptimal vitamin D status was defined by vitamin D serum level < 30 ng/ml, vitamin insufficiency by vitamin D serum level between 10 and 30 ng/ml and vitamin deficiency serum level < 10 ng/ml., Results: We included 77 subjects (52 patients with CD and 25 controls) with mean age of 38 years± 11. Most patients and controls had suboptimal levels of vitamin D (98% and 96% respectively) including vitamin D deficiency in 75% and 67%, respectively and vitamin D insufficiency in 25% and 33%, respectively. In univariate analysis, vitamin D deficiency was associated with disease flare-up (p=0.001), anemia (p=0.002), hypo-albuminemia (p=0.002), elevated C-reactive protein (CRP) (p=0.003), Crohn's Disease Activity Index (CDAI) (p<0.001), ileal location (p=0.04) and immunosuppressive therapy (p=0.01). In multivariate analysis, only CDAI was significantly associated with vitamin D deficiency (p=0.003, OR=9.33)., Conclusion: Vitamin D deficiency is common in Tunisian CD patients as well as in controls and is associated with disease activity.

Isolated hepatic tuberculosis is a rare form of extrapulmonary tuberculosis. We report an exceptional case of a 51-year-old female patient complaining from right upper abdominal quadrant pain, who underwent laparoscopic surgery for millimetric gallbladder polyps. Preoperative ultrasound hepatic morphology and biochemical hepatic tests revealed no abnormalities. There were no clinical patterns for an active tuberculosis. During surgery time, scattered sub-centimeter whitish nodular lesions were discovered on the upper surface of the liver. Although gallbladder pathological examination did not reveal any significant abnormalities, per surgery hepatic biopsy indicated the presence of a giant cell granuloma with caseous necrosis highly suggestive of hepatic tuberculosis. Treatment by anti-bacillary drugs according to local standard protocol was conducted with favorable outcomes. Therefore, diagnosis of hepatic tuberculosis may be considered in endemic countries in totally asymptomatic patients or complaining from unexplained and isolated abdominal pain, in absence of any morphologic or biochemical hepatic abnormalities.

Background: Hepatic hydrothorax is a less common complication of cirrhosis with an estimated prevalence of 10- 15%. In the vast majority of cases, ascites are also present but significant pleural effusion may develop in patients without ascites. Hepatic hydrothorax is associated with cirrhosis whatever its etiology. The prognosis of hepatic hydrothorax remains unclear and is closely related to available therapeutic options. The aim of our study is to determine the prevalence of hydrothorax in cirrhotic patients, detail its clinical and therapeutic characteristics, and study the evolutive profile of cirrhotic patients with hydrothorax by comparing it to those without hydrothorax. We also search predictive factors of development of this complication in cirrhotic patients., Methods: We conduct a retrospective and case-control study including 63 cirrhotic patients with hepatic hydrothorax hospitalized in gastroenterology department of Charles Nicolle hospital of Tunis, during a period of fiveteen years, from January 2000 to January 2015., Results: The prevalence of hydrothorax was 14.5%. The mean age was 62 ± 14 years (range, 22- 86 years). The sex ratio H/F was 1.52. Hepatic hydrothorax was symptomatic in 35 patients. It was right-sided in 60%, left-sided in 24% and bilateral in 16% of cases. Hydrothorax was on average size abundance in 54% of cases. It was transsudatif in 52.5% of cases. Hepatitis C was the most frequent cause of cirrhosis (54%). Our results show that hepatic hydrothorax was present with important ascites in 35 patients. Hydrothorax was significantly related to Child-Pugh C severity of cirrhosis (p=0.0001). Hydrothorax occurence was significantly associated with a low level of albumin (p=0.001), an important hyponatremia (p=0.001) and a low prothrombin rate (p=0.02). A therapeutic thoracentesis was performed in 57% of cases. Diuretics based on spironolactone and furosemide were indicated in 30 patients. Evolution was favorable in 19 patients. Refractory hepatic hydrothorax was present in 31 patients. Death, in the days which follow the hospitalisation, was in 13 patients. The 5-years survival rate was 60%. The mean survival time of patients with hepatic hydrothorax was 8.41 years against 10.75 years at patients without hepatic hydrothorax., Conclusion: Hepatic hydrothorax is a common complication in our study. The improvement of the prognosis of our patients would require a better therapeutic management and especially the possibility of orthotopic liver transplantation which is the optimal therapeutic option for patients with hepatic hydrothorax.

Introduction: The variceal bleeding, main complication of portal hypertension during cirrhosis, is associated with high early mortality riskestimated between 15 and 20%. This highlights the necessity of predictive models that allow identifying high-risk patients raising the issue of amore aggressive therapeutic care., Objective: To assess the performance of four scores for the prediction of cirrhotic patients' high early mortality risk due to digestive hemorrhageand to compare them to the Child-Pugh reference score., Methods: We collected 87 cirrhotic patients admitted to the Gastroenterology Department of Charles Nicolle Hospital for a high digestivehemorrhage by rupture of gastric or esophageal varicose veins., Results: 56 men and 31 women were included in this study. The average value of Rockall, Glasgow Blatchford, MELD and MELD-Na scores,was respectively equal to 6.19, 10.91, and 17.6 and at 20. Early mortality was 30%. The average value of all the scores was significantly higherwith the prematurely deceased patients (p<0.001). The MELD-Na score had higher sensitivity and specificity for the prediction of prematuremortality compared to the other scores but without statistical significantly difference (Area under the ROC curve: MELD-Na=0.867, p<0.001;Child-Pugh=0.809, p<0.001; Rockall=0.777, p=0.001; Glasgow-Blatchford=0.761, p<0.001; MELD=0.838, p<0.001). The predictive value of thecut-off MELD-Na score was equal to 19 with a sensitivity of 70% and a specificity of 82%., Conclusion: The studied four scores had a good predictive value of early mortality risk by varicose digestive hemorrhage with cirrhotic patients.

Background: The viral B reactivation is associated to deadly serious forms. There exist populations suffering this risk yet with a possibility of prevention through a pre-emptive treatment., Purposes: Establishing the diagnosis of a viral B reactivation. Identifying the patients with risk of exposure to viral B reactivation and implementing the means of prevention of viral reactivation., Methods: literature review, Results: the diagnosis of reactivation is not consensual. It is evoked facing a fast increase of aminotransferases with the ALAT superior to 5-10 times normal or superior to 3 times the basic value, an ascension of the HBV DNA within the serum, a reappearance of anti Hbc of IgM type with, most often, a weak title and /or a reversion Hbs. The reactivation depends on the type of treatment and of the viral B status. It was described under chemotherapy concerning the solid tumors particularly that of the breast, in haematology and increases with the resort to monoclonal antibody (anti-CD20). Under anti-TNFα a reactivation is possible within a variable deadline from the 1st to the 12th perfusion. Besides the type of treatment, the risk is more important with the patients Ag Hbs positive and correlated with the viremia. However, the patients having an occult hepatitis B or even a recovered from hepatitis are equally exposed to the risk of reactivation., Conclusion: viral reactivation is frequent since the larger use of immunosuppressive therapy, anti-TNFα and monoclonal antibody. The determination of the initial viral B status by a serology is indispensable. In order to indicate either surveillance or a preemptive treatment.

Background: Obesity raises such a healthcare matter throughout the world. Its management is not only complex but also most often multidisciplinary. The medico-dietary treatment is of inconstant efficiency and the surgical treatment, though more efficient, presents a considerable morbidity-death rate. The endoscopic treatment through intra-gastric balloon avails a seducing alternative namely accounting for surgery preparation., Aim: To assess the efficiency of the endoscopic treatment through gastric balloon, both in the short and long term, and this is accounting for weight loss as well as tolerance., Methods: We have carried out a retrospective study including the patients suffering from severe to morbid obesity and who had a gastric balloon implemented in our Endoscopy Unit between November 2005 and December 2007., Results: Twenty one patients were included. The average age was 32,19 ± 12,65 years with extremes of 16 and 52 years. Fifteen patients suffered from morbid obesity. The patients' average weight was 134, 52 ± 26,46 kg (extremes 88 and 194 kg). Some co-morbidity was found out with 15 patients. Te balloon implementation (Héliosphère®) was carried out with no incidents in all patients. Six months after the balloon implementation, the average weight loss was 17,5% and the average loss of over weigh was 37%. In biological level, we noted a normalisation of fasting glycaemia in 28,6 % of cases, of the cholesterolemia in 100 %, of the triglyceridemia in 33,33%, of the uraemia in 42,8% and hepatic tests in 50 % of the cases. The metabolic syndrome disappeared in 28,57 % of cases. The assessment after a 5-year-period was marked by the need to surgical treatment in 4 patients and this is due to the loss of efficiency of endoscopic treatment. A bad tolerance of gastric balloon was observed in 34 % of the cases, dominated by sicknesses. Only one patient presented incoercible sicknesses with ionic troubles as well as deshydrating requiring the precocious extraction of the balloon after 48 hours of its implementation., Conclusion: The endoscopic treatment through intra gastric balloon is well tolerated but efficiently limited in time. It might be recommended in preparation for a surgical treatment or in case of contre- indication or surgery refusal.

Background: Infections are frequent in cirrhotic patients. They are potentially severe, modifying pejoratively the natural history of the cirrhosis and are suppliers of a heavy mortality., Aim: To determine the predictive factors of hospital mortality in cirrhotic infected patients., Methods: We conducted a retrospective study including 97 cirrhotic patients hospitalized in the department of gastroenterology of Charles Nicolle's hospital, for a first infectious episode and not having received antibiotics in the previous 15 days. Clinico-biological, bacteriological, therapeutic and evolutionary data were collected. Scores were adopted and calculated such as the score of Child-Pugh, the score MELD (The Model for End-Stage Liver Disease) and the score SOFA (Sequential Organ Failure Assessment). These data allowed a descriptive study and an uni and multi-varied analysis., Results: The median age of the studied population was of 59 ± 12 years with a sex ratio of 0.83. The diabetes was the comorbidity most frequently associated with the cirrhosis (26.8 % of the cases) Viral aetiology of the cirrhosis was dominant (3/4 of the cases) especially the virus C (62.5 % of the cases). The clinical presentation of the infection was polymorphic with presence of symptoms connected to the infection and the other connected to the progression of the liver disease. The fever was absent in 3/4 of the cases. The identified infections were, in order of frequency, urinary, infection of ascite, bronchopulmonary, cutaneous and gynecological. The responsible germs were especially bacilli gram negative of intestinal origin. The estimated scores of gravity were: a score of Child-Pugh C in 60 % of the cases, an average score MELD in 18±8 points and a score average SOFA in 8 ± 4 points. Multivariate study found that only encephalopathy, bilirubin level more than 40 μmol/l and creatinin level more than 120 μmol/l was independent factors predicting mortality., Conclusion: Infection in cirrhotic patients was a severe and mortal complication. The hepatic encephalopathy, the hyper bilirubinemia and the renal failure are predictive of the hospital mortality. The use of the scores of gravity: Child-Pugh, MELD and SOFA would an important help for the decision to admit in intensive care unit any infected cirrhotic patient.

Background: Autoimmune hepatitis is chronic and uncommon disease. The pathogenesis is a complex process. Several triggers for autoimmune hepatitis particularly viral herpesviridae infection, which may induce the development of autoimmunity in predisposed individuals., Aim: Report a new case., Case Report: We report a case of 17-year- woman presented with autoimmune triggered by cytomegalovirus infection. Cytomegalovirus induced autoimmune hepatitis has not been reported previously. Evolution was favourable under antiviral treatment, corticosteroid and azathioprine.

Aim: To assess the diagnostic value of Fibrotest in comparison with liver biopsy, for the evaluation of hepatic fibrosis in patients with chronic hepatitis C., Methods: This prospective study included in 2 years (2006-2007), consecutive patients with chronic hepatitis C naive to treatment. Fibrotest and liver biopsy were performed. Receiver operating characteristics (ROC) curves , the sensitivity, specificity, positive and negative predictive values were used to assess the diagnostic value of Fibrotest in comparison with the METAVIR classification., Results: We recruited a total of 65 patients: 28 males and 37 females (mean age: 50 years); 92% of the patients had genotype 1. The histological fibrosis results were: 3.1% F0; 24.6% F1; 32.3% F2; 29.2% F3 and 10.8 % F4. The diagnostic value of Fibrotest in the detection of significant fibrosis (F2-F4) was 0. 87. A score > 0.5 has a sensitivity of 85. 1%, a specificity of 72. 2%, a positive predictive value of 88. 9%,and a negative predictive value of 65%. The diagnostic value of Fibrotest in the detection of cirrhosis (F4) was 0. 85. There were 13/65 cases of discordance (20%) for fibrosis, 4 cases were attributable to biopsy and 6 cases to Fibrotest. The discordance was unexplained in 3 cases. the size of biopsy< 15 mm [OR=2. 82, 95% CI, 1. 3-6. 07; p = 0. 008] and the stage of fibrosis F0, F1, F2 [OR =3. 35 , 95% CI, 1. 1-10. 2; p=0. 03] were considered as risk factors of discordance in multivariate analysis., Conclusion: This prospective study confirmed the good diagnostic value of Fibrotest as compared with the histological analysis of liver biopsy.