A 3'-untranslated region variant (rs2289046) of insulin receptor substrate 2 gene is associated with susceptibility to nonalcoholic fatty liver disease.

PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is an increasing global health concern defined by excessive hepatic fat content in the absence of excessive alcohol consumption. Regarding the key role of insulin and insulin resistance in NAFLD, we investigated whether insulin receptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) gene variants were associated with NAFLD risk. METHODS: In this case-control study, 305 subjects including 151 cases with biopsy-proven NAFLD and 154 controls were enrolled. All the subjects were genotyped for IRS1 (rs1801278) and IRS2 (rs2289046) gene variants using PCR-RFLP method. RESULTS: Our findings showed that the IRS2 rs2289046 "GG+AG" genotype compared with "AA" genotype to be a marker of decreased NAFLD susceptibility and the difference remained significant even after adjustment for confounding factors including age, BMI, sex, smoking status, systolic blood pressure, and diastolic blood pressure (P=0.014; OR=0.50, 95%CI= 0.29-0.87). Furthermore, the IRS2 "G" allele was significantly underrepresented in the cases with NAFLD than controls (P=0.026 ; OR=0.62, 95%CI=0.41-0.94). However, no significant difference was found for IRS1 rs1801278 gene variant. CONCLUSIONS: This study suggests, for the first time, that the IRS2 gene rs2289046 variant may play a role in NAFLD susceptibility. Nevertheless, this observation warrants further investigations in other populations.

Diastolic dysfunction and severity of cirrhosis in nonalcoholic cirrhotic patients.

Background. In this study, we evaluated the association between diastolic dysfunction severity and severity of cirrhosis in nonalcoholic cirrhotic patients. Methods. This cross-sectional study was conducted on all nonalcoholic cirrhotic patients who were admitted in Rasht Razi hospital the Cancer of Guilan Province, north of Iran, from January 2011 to March 2012. Severity of cirrhosis was evaluated by Child-Pugh score. A 12-lead surface ECG and echocardiographic studies were performed. We used a HDI 3000 (Philips ATL, Bothell, WA, USA) equipped with 2 to 4 MHz probes. Diastolic function was determined by an expert cardiac sonographer. Data were analyzed by SPSS for win (version16). A P value less than 0.05 was considered significant. Results. Sixty-tree percent of patients were male. The mean age of patients was 52.78 ± 15.2 years. 22%, 38%, and 40% of patients were considered as child class A, B, and C, respectively. There was a significant relation between diastolic dysfunction and disease duration (P = 0.001), female gender (P = 0.004), age > 60 years (P = 0.045), and severity of cirrhosis (P = 0.048). On multivariate analysis, decreased E/A ratio (P = 0.03) and disease duration (P = 0.02) showed an independent significant relation. Conclusion. According to the relation between severity of cirrhosis and diastolic dysfunction, we recommend cardiac assessment in all child B and C cirrhotic patients.

Hepatitis B virus surface protein mutations clustered mainly in CTL immune epitopes in chronic carriers: results of an Iranian nationwide study.

Mutations within the coding region of hepatitis B surface antigen (HBsAg) have been found naturally in chronic carriers. To characterize the mutations of HBsAg from Iranian chronic carriers who were vaccine and/or medication naive. The surface genes from 360 patients were amplified and directly sequenced. The distribution of amino acid substitutions was classified according to different immune epitopes of the surface protein. All isolates belonged to genotype D. 222 (61.6%) of 360 patients contained at least one amino acid substitution. 404 (74.5%) of 542 amino acid changes occurred in different immune epitopes of HBsAg, of which 112 (27.7%) in 32 residues of B-cell epitopes (62 in the 'a' determinant); 111 (27.4%) in 32 residues of T helper; and 197 (48.7%) in 32 residues inside cytotoxic T lymphocyte (CTL) epitopes. One Th (186-197) and two CTL (28-51 and 206-215) epitopes were found to be hotspot motifs for the occurrence of 213 (52.7%) substitutions. 20 stop codons were identified in different epitopes. There was a significant association between amino acid substitutions and anti-HBe seropositivity; however, the correlation between such changes with viral load and ALT levels was not significant. In chronic hepatitis B virus(HBV) carriers, positive selection in particular outside the 'a' determinant appeared to exert influence on the surface proteins. These changes could be immune escape mutations naturally occurring due to the host immune surveillance especially at the T-cell level.

Distribution of hepatitis C virus genotypes in haemodialysis patients of Guilan, northern Islamic Republic of Iran.

The hepatitis C virus (HCV) infection among patients undergoing haemodialysis is high. The aim of this study was to identify the HCV genotypes among chronic haemodialysis patients who were HCV positive in Guilan province, northern Islamic Republic of Iran. All patients on haemodialysis at Guilan haemodialysis centres were enrolled. Enzyme-linked immunosorbent assay and polymerase chain reactio testing were performed. Out of 514 enrolled patients, 11.9% were serologically HCV positive and 6.2% had positive HCV-RNA. HCV genotypes were determined with HCV genotype-specific primers. The most frequent genotypes were 1a (59.4%) and 3a (40.6%). There was no significant relationship between virus genotypes and sex or age. The HCV genotype pattern among haemodialysis patients in Guilan province was different from other countries of the Middle East and was more similar to North American and European countries where genotype 1 is predominant.

Distribution of hepatitis C virus genotypes in haemodialysis patients of Guilan, northern Islamic Republic of Iran

The incidence of hepatitis C virus [HCV] infection among patients undergoing haemodialysis is high. The aim of this study was to identify the HCV genotypes among chronic haemodialysis patients who were HCV positive in Guilan province, northern Islamic Republic of Iran. All patients on haemodialysis at Guilan haemodialysis centres were enrolled. Enzyme-linked immunosorbent assay and polymerase chain reaction testing were performed. Out of 514 enrolled patients, 11.9% were serologically HCV positive and 6.2% had positive HCV-RNA. HCV genotypes were determined with HCV genotype-specific primers. The most frequent genotypes were la [59.4%] and 3a [40.6%]. There was no significant relationship between virus genotypes and sex or age. The HCV genotype pattern among haemodialysis patients in Guilan province was different from other countries of the Middle East and was more similar to North American and European countries where genotype 1 is predominant

Furazolidone, amoxicillin and omeprazole with or without bismuth for eradication of Helicobacter pylori in peptic ulcer disease.

BACKGROUND/AIMS: Furazolidone has been introduced as an effective drug against Helicobacter pylori infection in Iran, but intolerable side effects may limit its use. The aim of this study was to compare quadruple and triple furazolidone-based regimens to achieve an economically affordable regimen with acceptable success rate and fewer side effects. METHODS: Patients with Helicobacter pylori positive peptic ulcer disease were randomly allocated into two groups: amoxicillin 1 g b.i.d., furazolidone 200 mg b.i.d. and omeprazole 20 mg b.i.d. with or without bismuth subcitrate 240 mg b.i.d. for two weeks (amoxicillin, furazolidone, omeprazole, bismuth and amoxicillin, furazolidone, omeprazole regimens, respectively). Helicobacter pylori eradication was confirmed by 13C-urea breath test 12 weeks after the end of therapy. RESULTS: Eighty-six patients were enrolled, but 16 patients discontinued their therapy or follow-up. The eradication rates with amoxicillin, furazolidone, omeprazole, bismuth and amoxicillin, furazolidone, omeprazole were 85.3% and 61.1% by per-protocol analysis, respectively (p=0.02) and 67.4% and 51.2% by intention-to-treat analysis, respectively (p<0.05). The most frequent adverse effects in the two study groups were weakness, nausea, anorexia, and dizziness, and no significant differences between the groups were shown. CONCLUSIONS: Based on the results in this study, furazolidone-based triple therapy (without bismuth) is not recommended for Helicobacter pylori eradication because of the lower eradication rate and unchanged frequency of adverse effects. Thus, we recommend furazolidone, amoxicillin and omeprazole in combination with bismuth for treatment of Helicobacter pylori.

Assessment of propofol usefulness as an anesthetic agent during colonoscopy.

BACKGROUND Propofol is used as a sedative drug during colonoscopy. In this study we analyzed the adverse effects of propofol (i.e., hemodynamic and respiratory) on patients who underwent colonoscopies. METHODS This study was performed in Qom Province, Iran. In this study, 125 patients (63 females, 62 males) were enrolled. Study patients were administered (0.5-1.5 mg/kg) intravenous propofol by an anesthesiologist. Oxygen saturation and blood pressure were recorded at three minute intervals. We used the American Society of Anesthesiology (ASA) classification to stratify patients by risk prior to the procedure. For statistical analysis, the chi-square and paired t-tests were used. A p -value less than 0.05 was considered significant. RESULTS Patients' mean age was 45.36 ± 16.19 years. ASA-I comprised 25.6% of study patients and 74.4% were categorized as ASA-II. Hypopnea occurred in 56.8% of patients and was prolonged in 32.4%. Of the study patients, 5.6% developed hypoxemia which was successfully controlled by the administration of nasal oxygen and no need for mechanical ventilation. The mean arterial blood pressure (p < 0.0001), oxygen saturation (p < 0.0001) and heart rate (p < 0.0001) significantly decreased during colonoscopy. The occurrence of hypopnea significantly increased in patients with pre-procedure oxygen saturation levels ≤ 95% (p < 0.02), age <50 years (p < 0.0001) and ASA class II (p < 0.0001) Agitation, hypotension and cough were seen in 1.6%, 1.6% and 0.8% of patients, respectively. CONCLUSION Propofol has a short half life that enables faster recovery of normal neurologic and social functions we recommend the use of propofol under supervision of anesthesiologist or a trained gastroenterologist.