Relationship between IL28B gene rs8099917 polymorphism and SVR in Turkish patients with hepatitis C virus genotype 1.

BACKGROUND AND OBJECTIVE: The hepatitis C virus (HCV) which infects 3% of the world's population is a global challenge. Recently, genome-wide association studies (GWAS) have identified that the IL28B gene rs8099917 polymorphism was associated with the response to the pegylated-interferon alpha/ribavirin (PegIFNα/RBV) combination therapy in patients infected with HCV genotype 1. IL28B gene rs8099917 polymorphism should be determined before beginning treatment of HCV-infected patients to predict an individual's response. The aims of this study were to analyze the correlation between IL28B gene rs8099917 (T/G) polymorphism and PegIFNα/RBV therapy outcome in the Turkish population. METHODS: Genotypes of the IL28B gene rs8099917 (T/G) single nucleotide polymorphism (SNP) were determined in 308 patients with HCV infection by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. One group consisted of 148 patients with a sustained virological response (SVR), whereas the second group consisted of 160 nonresponders (non-SVR). RESULTS: Allele and genotype associations of IL28B gene rs8099917 polymorphism with a sustained virological response were observed in comparisons between the SVR and non-SVR groups (P<0.001). In addition, the characteristics of the subjects did not differ between these two groups except for age and fibrosis stage (P<0.05). Additionally, neither SVR nor rs80999917 genotypes were associated by HCV RNA levels. CONCLUSIONS: In conclusion, the rs8099917 polymorphism was thus found strongly associated with a sustained virological response to therapy in Turkish patients infected with HCV genotype 1. Consequently, we suggest determining IL28B gene rs8099917 polymorphism of patients with HCV genotype 1 before onset of treatment.

p53 codon 72 polymorphism is associated with susceptibility to hepatocellular carcinoma in the Turkish population: a case-control study.

The tumor suppressor p53 gene plays a crucial role in preventing carcinogenesis through its ability to induce cell cycle arrest and apoptosis following DNA damage and oncogene activation. A guanine (G)/cytosine (C) common single nucleotide polymorphism (SNP) at second position of codon 72 in exon 4 of p53 gene determines a arginine (Arg) to proline (Pro) (Arg72Pro) aminoacidic substitution within the proline-rich domain of p53 protein. Arg72 and Pro72 allele are different from a biochemical and biological point of view and many reports suggest that they can modulate individual cancer susceptibility. To determine the association of the p53 Arg72Pro polymorphism with the risk of hepatocellular carcinoma (HCC) development in a Turkish population, a hospital-based case-control study was designed consisting of 119 subjects with HCC and 119 cancer-free control subjects matched for age, gender, smoking and alcohol status. The genotype frequency of the p53 Arg72Pro polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Our data shows that the Pro/Pro genotype of the p53 Arg72Pro polymorphism is associated with increased risk of HCC development in this Turkish population (OR = 3.20, 95% CI: 1.24-8.22, P = 0.02). Furthermore, according to stratified analysis, a significant association was observed between the homozygote Pro/Pro genotype and HCC risk in the subgroups of male gender (OR = 3.01, 95% CI: 1.14-7.97, P = 0.03) and patients with hepatitis B virus (HBV)-related HCC (OR = 4.04, 95% CI: 1.46-11.15, P = 0.007). Because our results suggest for the first time that the Pro/Pro homozygote of p53 Arg72Pro polymorphism may be a genetic susceptibility factor for HCC (especially in the male gender and HBV-infected patients) in the Turkish population, further independent studies are required to validate our findings in a larger series, as well as in patients of different ethnic origins.

No association of pre-microRNA-146a rs2910164 polymorphism and risk of hepatocellular carcinoma development in Turkish population: a case-control study.

AIM: MicroRNAs (miRNAs) are an abundant class of small non-protein coding RNAs with posttranscriptional regulatory functions as tumor suppressors and oncogenes. Aberrant expression and structural alteration of miRNAs are considered to participate in tumorigenesis and cancer development. It has been suggested that the presence of single nucleotide polymorphisms in precursor miRNAs (pre-miRNAs) can alter miRNA processing, expression, and/or binding to target mRNA and represent another type of genetic variability that can contribute to the susceptibility of human cancers. A G/C polymorphism (rs2910164), which is located in the sequence of miR-146a precursor, results in a change from G:U to C:U in its stem region. METHODS: To determine the association of the miR-146a rs2910164 polymorphism on the risk of hepatocellular carcinoma (HCC) development in Turkish population, a hospital-based case-control study was designed consisting of 222 subjects with HCC and 222 cancer-free control subjects matched on age, gender, smoking and alcohol status. The genotype frequency of miR-146a rs2910164 polymorphism was determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: No statistically significant differences were found in the allele or genotype distributions of the miR-146a rs2910164 polymorphism among HCC and cancer-free control subjects (p>0.05). CONCLUSION: Our results demonstrate that the miR-146a rs2910164 polymorphism has no major role in genetic susceptibility to hepatocellular carcinogenesis, at least in the population studied here. Independent studies are needed to validate our findings in a larger series, as well as in patients of different ethnic origins.

Atherosclerosis and acetylsalicylic acid are independent risk factors for hemorrhage in patients with gastric or duodenal ulcer.

OBJECTIVE: Risk factors for hemorrhage due to gastric and/or duodenal ulcer in patients diagnosed by upper gastrointestinal (GI) endoscopy were investigated in the present study. METHODS: Medical records of 350 patients (226 males, 124 females) diagnosed as duodenal or gastric ulcers by GI endoscopy in the gastroenterology clinic were scanned retrospectively. Upper GI hemorrhage was detected in 92 patients by upper endoscopic examination. The medical history of non-steroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid (ASA) usage and the presence of coronary artery disease (CAD) were investigated in all patients with or without hemorrhage. Results were evaluated by Chi-square test and logistic regression analysis. RESULTS: The mean age of the patients was 50.4 ± 15.7 years (range: 25 to 82 years). Hemorrhage due to gastric or duodenal ulcer was identified in 92 patients (26%). Mean age was 64.6 ± 11.4 years in patients with hemorrhage and 45.7 ± 13.9 years in patients without hemorrhage. ASA usage was more common than NSAID in patients with ulcer hemorrhage (NSAID usage n=35 (40%); ASA usage n=51 (60%); p=0.035). Hemorrhage was reported in 20% of the females and in 28% of the males who have ulcer (p=0.055). Risk factors for hemorrhage were CAD (OR:24.75, 95% CI=1.6-96.7, p=0.001), ASA usage (OR:9.76, 95% CI=2.1-37.5, p=0.021), NSAID usage (OR: 4.72, 95%CI=1.1-16.5, p=0.032), age (OR: 11.59, 95% CI= 2.7-12.1, p=0.001), and male gender (OR: 2.56, 95% CI= 0.8, 9.6, p=0.052). CONCLUSION: Advanced age, atherosclerosis, male gender and NSAID administration (particularly aspirin) are the major risk factors of upper GI hemorrhage in patients with gastric and/or duodenal ulcer.

New therapeutic option with N-acetylcysteine for primary sclerosing cholangitis: two case reports.

Primary sclerosing cholangitis is a progressive, cholestatic hepatic disease of unknown etiology. It is characterized by progressive inflammation, destruction, and fibrosis of the intrahepatic and extrahepatic bile ducts. Several medical therapies have been tried such as penicilamin, colchicine, methatraxate, cyclosporine, tacrolimus, and ursodeoxycholic acid. Treatment with mucolytic agents in excessively high viscosity conditions appears to have an important role. N-acetylcysteine (NAC), as a mucolytic agent, may fascilitate the drainage in partial obstructions by decreasing the mucous viscosity. We suggest that NAC and ursodeoxycholic acid have markedly positive effects on the clinical course of cholangitis and cholestasis when used together by affecting bile viscosity. Here, we present two cases treated with NAC. NAC capsul therapies at 800 mg/day were administered to two patients with primary sclerosing cholangitis. Clinical and laboratory parameters of patients saw significant improvement.

No association of NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism and risk of hepatocellular carcinoma development in Turkish subjects.

NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of numerous quinoid compounds into their less toxic form, thus NQO1 protecting cells against oxidative stress. The gene coding for NQO1 has a single nucleotide polymorphism (C-->T) at nucleotide position 609 (proline to serine substitution at position 187 in amino acid sequence (P187S)) (rs1800566) of the NQO1 cDNA which results in very low enzimatic activity, so it would be expected that individuals with the homologous NQO1 C609T polymorphism would have a susceptibility developing cancer. Previous studies of the association between functional NQO1 C609T polymorphism and several human cancers have had mixed findings but association of NQO1 C609T polymorphism with hepatocellular carcinoma (HCC) development has yet to be investigated. In this study, we aim to evaluate the the association of NQO1 C609T with the risk of hepatocellular carcinoma (HCC) development among Turkish population. NQO1 C609T polymorphism was investigated in 167 confirmed subjects with HCC and 167 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. There is no association between the allel or genotype of NQO1 C609T polymorphism and HCC development risk in the Turkish subjects examined (p>0.05). Our result demonstrate for the first time that the NQO1 C609T polymorphism is not a genetic susceptibility factor for HCC in the Turkish population. Independent studies are need to validate our findings in a larger series, as well as in patients of different ethnic origins.

Endoscopic alcohol injection therapy of giant gastric leiomyomas: an alternative method to surgery.

Leiomyomas are the most common benign mesenchymal tumours of the upper gastrointestinal tract. They rarely cause symptoms when they are smaller than 5 cm in diameter. Observation with repeated endoscopies is recommended in asymptomatic patients with small lesions. Surgical resection remains the main therapy option for symptomatic and complicated patients. The treatment of esophageal leiomyoma has been enhanced by improvements in diagnostic and therapeutic endoscopic techniques; however, the same cannot be said for gastric leiomyoma management. The present article describes the management of two cases involving giant gastric leiomyomas that were  successfully treated using endoscopic injection of alcohol. To the authors' knowledge, the present study is the first report of the treatment of such hemorrhagic gastric tumours using this alternative and low-cost technique. Endoscopic local ethanol injection may be the treatment of choice in carefully selected patients with hemorrhagic leiomyomas of the upper gastrointestinal tract.

The Diagnostic Value of Endoscopic Balloon Catheter Usage for Detecting Early-Stage Primary Sclerosing Cholangitis in Endoscopic Retrograde Cholangiopancreatography: A Case Report.

A 34-year-old woman was admitted to our clinic with abdominal pain, jaundice and pruritus. Endoscopic retrograde cholangiopancreatography was performed for cholestasis. Endoscopic retrograde cholangiopancreatography (ERCP) was judged as normal, after a standard ERCP cannula was used for the cholangiogram. However, marked canalicular irregularities were identified in cholangiography when pressurized contrast agent was administrated via balloon catheter. This cholangiographic view was thought to reveal an early-stage alteration of sclerosing cholangitis. Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by destruction and fibrosis of the bile ducts. The diagnosis of PSC is based on typical cholangiographic findings, supported by nonspecific clinical signs and symptoms, cholestatic liver biochemical tests, and liver biopsy. Cholangiography is considered to be the gold standard for the diagnosis of PSC. The diagnosis is easy when diffuse multifocal biliary strictures, the hallmarks of the disease, resulting in a 'beaded' appearance on ERCP is detected. However, it may reveal a normal image in an early stage of the disease when bile duct changings are not prominent. We think that balloon catheter ERCP appears to facilitate the diagnosis of early-stage primary sclerosing cholangitis.

Influence of CYP2C19 functional polymorphism on Helicobacter pylori eradication.

BACKGROUND/AIMS: Proton pump inhibitors are mainly metabolized by cytochrome P450 2C19 in the liver. Recently, some studies have shown that the acid suppressing effect of proton pump inhibitors are influenced by a functional polymorphism of cytochrome P450 2C19. The aim of the present study was to investigate the effect of cytochrome P450 2C19 polymorphism on Helicobacter pylori eradication in patients who received proton pump inhibitors based triple therapy. METHODS: We determined the incidence of cytochrome P450 2C19 genotypes and the effect of cytochrome P450 2C19 genotypes on Helicobacter pylori eradication rates in 105 patients with Helicobacter pylori-positive chronic gastritis. Upper endoscopic procedure and gastric biopsies were performed in all patients. Helicobacter pylori was demonstrated histologically. Lansoprazole, amoxicillin and clarithromycin twice a day for 14 days were prescribed for those found to be infected with Helicobacter pylori. More than one month after the medication, a 13C urea breath test was conducted to examine the success or failure of the eradication treatment. Cytochrome P450 2C19 polymorphism was analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The genotypes of cytochrome P450 2C19 were classified into the three groups, as rapid extensive metabolizer, intermediate metabolizer and poor metabolizer. In our patient population, the frequencies of rapid extensive metabolizer, intermediate metabolizer and poor metabolizer were 72%, 23% and 5%, respectively. The eradication rate was 70.0% for rapid extensive metabolizer, 92% for intermediate metabolizer and 80% for poor metabolizer. The eradication rate was highest in intermediate metabolizer patients. CONCLUSIONS: The present study confirmed the low eradication rate for rapid extensive metabolizer. Our findings provide evidence that the cytochrome P450 2C19 genotype is useful to predict the success of treatment. For the rapid extensive metabolizer group, alternative regimens can be tried to increase the Helicobacter pylori eradication rates.

Potential benefits of combined N-acetylcysteine and ciprofloxacin therapy in partial biliary obstruction.

This study investigates the potential benefits of antibiotics and N-acetylcysteine (NAC), a mucolytic agent, in patients who are candidates for endoscopic retrograde cholangiopancreatography (ERCP) due to partial bile duct obstruction. In total, 102 patients who had choledocholithiasis and choledochal dilatations by abdominal ultrasonography were included in the study. The patients were divided into placebo and NAC therapy groups. Physiological saline (equal volume with NAC solution) and ciprofloxacin (2 × 200 mg/d intravenously) were administered to the placebo group, and NAC (1800 mg/d intravenously) and ciprofloxacin (2 × 200 mg/d intravenously) were administered to the NAC group. In both groups, treatment protocols were administered for 7 days before ERCP. Total and direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), C-reactive protein (CRP), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), white blood cell (WBC) count, and neutrophil percent (NE%) levels were measured before the 7-day treatment protocol. The same measurements were also evaluated before ERCP. In the NAC group, the levels of ALP, GGT, WBC, CRP, and NE% decreased significantly (P < .001), whereas a significant decrease did not occur in the placebo group. The combined usage of NAC and ciprofloxacin can be an alternative therapeutic option until ERCP is performed in partial cholestatic patients.

The significance of E266K polymorphism in the NOD1 gene on Helicobacter pylori infection: an effective force on pathogenesis?

The severity of Helicobacter pylori-related diseases varies greatly among infected individuals and seems to be influenced by both host and bacterial factors. Infection with a cytotoxin-associated gene pathogenicity island (Cag PAI)-positive H. Pylori strain causes a higher grade of gastric mucosal inflammation than an infection caused by a negative strain. Furthermore, such an infection is associated with severe atrophic gastritis and gastric adenocarcinoma. NOD1 protein is a cytosolic pattern recognition receptor that responds to peptidoglycan delivered by H. Pylori cag pathogenicity island. The aim of this study is to investigate whether the presence of the NOD1 G796A polymorphism has any influence on the clinical outcomes of Cag PAI-positive H. Pylori. Both Helicobacter pylori and CagA-positive 150 patients were considered eligible for the study. In this selected group, NOD1 G796A was detected by using polymerase chain reaction/restriction fragment length polymorphism. Activity and severity of gastritis, atrophy, intestinal metaplasia and Helicobacter pylori density were assessed in body and antral biopsies. Also post-therapy controls for predicting Helicobacter pylori persistence were done. The correlations of these parameters were determined by SPSS 15 packet program for statistical analysis. Of the 150 CagA-positive patients, 57 had (38%) heterozygote (GA), and 29 had (19.3%) homozygote (AA) mutant variants of NOD1. The other 64 patients had (42.7%) wild-type DNA(GG). NOD1 796A allele carriers had higher risk for antral atrophy (OR = 13.35, 95% CI = 5.12-34.82) and antral intestinal metaplasia (OR = 2.71, 95% CI = 1.26-5.80). Carriage of the single nucleotide polymorphism of NOD1 G796A proved to be a significant risk factor for the Helicobacter pylori therapy failure (OR = 4.62, 95% CI = 1.67-12.79). Our results suggest that carriage of the NOD1 G796A mutation increases the susceptibility of gastric epithelial cells for intestinal metaplasia and atrophy when infected by CagA-positive Helicobacter pylori strains. Additionally, it increases the ratio of eradication failure.

Recurrent hypersplenism caused by giant accessory spleen due to portal hypertension after splenectomia.

Splenectomy is one of the primary choices of treatment in immune thrombocytopenic purpura. However, the disease may relapse despite splenectomy. One of the leading causes of relapse is the presence of accessory spleen, which may become enlarged significantly with underlying pathologies such as presence of portal hypertension. The accessory spleen, which will inevitably enlarge in time, may grow significantly within a short period of time in the presence of portal hypertension and may thus be misdiagnosed as a tumoral mass. Presence of ectopic spleen should be borne in mind in patients diagnosed with immune thrombocytopenic purpura with relapsing hypersplenism following splenectomy. This article discusses a patient developing portal hypertension secondary to chronic liver disease and presenting with a significantly enlarged accessory spleen as well as hypersplenism findings.

Negative correlation between viral load and HBsAg levels in chronic HBV-infected patients.

The objective of this study is to reveal the relationship between viral load (as HBV DNA) and HBsAg levels. Ninety-two chronically HBV-infected patients were included in the study. The patients were divided in two different groups: the cirrhotic group (n = 32) and the non-cirrhotic group (n = 60). The correlation between study groups was also examined with regard to HBeAg status. Hepatitis B viral markers (HBsAg, HBeAg, Anti-HBs, anti-HBc and anti-HBe) and HBV viral load of the patients were measured. A significant negative correlation between HBV DNA and HBsAg levels was found in the non-cirrhotic group (p < 0.01). The anti-HBc level was higher in the non-cirrhotic group than in the cirrhotic group (p < 0.016). The viral load was significantly higher in HBeAg (+) patients in comparison with HBeAg (-) cases (p < 0.0001). The HBsAg level was low in HBeAg (+) patients, whereas it was higher in HBeAg (-) cases (p < 0.001). In conclusion, a significant negative correlation between viral load and HBsAg levels was detected in the non-cirrhotic chronically HBV-infected group. Therefore, concomitantly low HBsAg and HBV DNA levels may indicate a better prognosis compared to high HBsAg and low HBV DNA levels.