Mustafa Yakut

Serum vitamin B12 and folate status in patients with inflammatory bowel diseases

BACKGROUND The aims of this study were to investigate the prevalence of serum vitamin B(12) and folate abnormalities in patients with inflammatory bowel diseases (IBD) and to identify risk factors associated with B12 and folate abnormalities in this entity. METHODS 138 patients with IBD (45 Crohns disease and 93 ulcerative colitis) and 53 healthy subjects were enrolled into the study. Fasting serum B12 and folic acid levels were measured and clinical data regarding inflammatory bowel diseases were gathered. RESULTS While the mean serum B(12) concentration in CD patients was 281+/-166pg/ml, the mean serum vitamin B12 concentration in UC patients was 348+/-218pg/ml (p=0.224). The number of patients with vitamin B12 deficiency in the CD group was greater than the number of patients with UC [n=10 (22%) vs. n=4 (7.5%), p=0.014]. The number of patients (n=10, 22%) with B12 deficiency in the CD group was also greater than controls (n=4, 7.5%) (p=0.039). With regard to folate levels, the median serum folate level was 7.7+/-5.3ng/ml in CD patients, 8.6+/-8.3ng/ml in UC patients and 9.9+/-3.3ng/ml in the control group (p=n.s.). Patients with a prior ileocolonic resection had an abnormal B12 concentration compared to patients without surgery (p=0.008). In CD patients, ileal involvement was the only independent risk factor for having a low folate level. CONCLUSION Serum vitamin B12 and folate deficiencies are common in patients with CD compared to UC patients and controls. In CD patients, prior small intestinal surgery is an independent risk factor for having a low serum vitamin B12 level.

Diagnostic and prognostic role of serum glypican 3 in patients with hepatocellular carcinoma

α‐Feto protein (AFP) is the widely used tumor marker in the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to assess the diagnostic and prognostic validity of a novel marker, serum Glypican‐3 (GPC3) and to compare AFP in patients with HCC. One hundred and twenty‐eight patients (75 patients with HCC, 55 patients with cirrhosis, and 28 healthy controls) were included in this study. Cut‐off value of GPC3 was 3.9 pg/ml. AFP was divided into four subgroups, according to cut‐off values with 13, 20, 100, and 200 ng/ml. Sensitivity, specificity, and positive and negative predictive values of GPC3 and AFP13, AFP20, AFP100, AFP200 subgroups and also GPC3+AFP13, GPC3+AFP20, GPC3+AFP100, GPC3+AFP200 combinations were compared. Serum GPC3 levels were significantly higher in patients with HCC and cirrhosis compared with control subjects (P<0.05). The median serum GPC3 levels were 3.9 pg/ml in controls, 5.51 pg/ml in patients with cirrhosis, and 5.13 pg/ml in those with HCC. The median serum AFP levels were 1.37 ng/ml in controls, 2.32 ng/ml in cirrhotics, and 50.65 ng/ml in HCC patients. The sensitivity, specificity, and positive and negative predictive values of GPC3 was 61.33, 41.82, 58.97, and 44.43%, respectively. The values for AFP were 68.57, 94.55, 94.12, and 70.27%, respectively. There was no correlation between GPC3 levels and prognostic parameters. GPC3 is not a useful diagnostic and prognostic marker for HCC. J. Clin. Lab. Anal. 25:350–353, 2011.

Diagnostic and Prognostic Validity of Golgi Protein 73 in Hepatocellular Carcinoma

We regret to inform you that the criticism raised by the Editorial Board is correct concerning the similarity between some parts of the texts present in our article published in Digestion [2011;83:83–88], and the papers in the Journal of Hepatology [2005;43:1007–1012] and in Hepatology [2009;49:1421–1423], although the research data are completely independent. We apologize for this unfortunate error, which was established during the writing process of the manuscript by the author Harun Erdal. Although the final version of the submitted paper had been examined by all authors, they failed to recognize the ‘transferred parts’ of the papers in the Journal of Hepatology [2005;43:1007–1012] and in Hepatology [2009;49:1421–1423]. Thus, for the sake of scientific clarity and based on the above-mentioned facts, we prefer to retract our paper Diagnostic and Prognostic Validity of Golgi Protein 73 in Hepatocellular Carcinoma. Digestion 2011;83:83–88 (DOI:10.1159/000320379). Authors, Hasan Özkan Harun Erdal Hüseyin Tutkak Zihni Karaeren Mustafa Yakut Osman Yüksel Seyfettin Köklü

Entecavir Treatment of Chronic Hepatitis D

BACKGROUND Hepatitis D virus (HDV) requires hepatitis B surface antigen (HBsAg) to propagate infection and cause disease. Entecavir is a nucleoside analog with potent antiviral efficacy, and in the woodchuck animal model it also decreased hepatitis B virus (HBV) cccDNA and woodchuck surface antigen. The aim of this study was to investigate the efficacy of entecavir in chronic hepatitis D (CHD). METHODS This single-center study was conducted in patients with compensated liver disease. All patients had to have detectable hepatitis HDV RNA and elevated levels of alanine aminotransferase (ALT). Entecavir was given at a dosage of 1 mg/d for 1 year. The primary end point was achievement of undetectable HDV RNA at the end of treatment. RESULTS Thirteen consecutive patients were assessed. All patients had detectable HDV RNA, and 8 had detectable HBV DNA at baseline. At the end of treatment, HBV DNA became undetectable in all patients (P = .001). No significant decline in HDV RNA, ALT, or quantitative HBsAg levels was observed. The primary end point of undetectable HDV RNA at the end of treatment was achieved in 3 patients who had significantly lower baseline HDV RNA levels than nonresponders (2.99 log(10) copies/mL ± .70 vs 4.68 ± .97; P = .0185). In all 3 patients, ALT levels were also normal at the end of treatment. CONCLUSIONS One year of entecavir treatment is ineffective in CHD. Any generalized beneficial effect of nucleoside/nucleotide analog treatment may necessitate prolonged treatment. Patients with CHD with HBV dominance, which is likely to occur in the later phases of CHD, may be a reasonable patient cohort in which to target nucleoside/nucleotide analog therapy.

Clinical Profiles, Endoscopic and Laboratory Features and Associated Factors in Patients with Autoimmune Gastritis

Background/Aims: Autoimmune gastritis (AIG) may predispose to gastric carcinoid tumors or adenocarcinomas and may also cause unexplained iron and/or vitamin B12 deficiency. The aims of this study were to explore clinical manifestations, endoscopic findings and laboratory features of patients with AIG. Methods: 109 patients with AIG were enrolled into the study. In addition to demographic and clinical data, gastric lesions, serum gastrin, vitamin B12, antiparietal cell antibody (APA), current Helicobacter pylori status, and anti-H. pylori IgG were also investigated. Results: The mean age of the patients was 53.06 ± 12.7 years (range 24–81; 72 (66.1%) women). The most common main presenting symptom was abdominal symptoms in 51 patients, consultation for iron and/or vitamin B12 deficiency in 36, and non-specific symptoms including intermittent diarrhea in 15 patients. Endoscopic lesions were detected in 17 patients, hyperplastic polyps in 8, gastric carcinoid tumor in 4, fundic gland polyps in 3, and adenomatous polyps in 2 patients. H. pylori was negative in all patients in biopsy specimens; however, anti-H. pylori IgG was positive in 30 (27.5%) patients. 91 patients (83.4%) were positive for APA. Conclusion: In patients with AIG, the main symptoms prompted for clinical investigation were: abdominal symptoms, iron/B12 deficiency and non-specific symptoms. 20% of patients with AIG had various gastric lesions including type I gastric carcinoids. None of the patients were positive for H. pylori by means of invasive tests; however, anti-H. pylori IgG was found in 27.5% of patients. Patients referring with non-specific abdominal symptoms such as bloating, diarrhea and iron/B12 deficiency should be investigated for the presence of AIG.

The association between precancerous gastric lesions and serum pepsinogens, serum gastrin, vascular endothelial growth factor, serum interleukin-1 Beta, serum toll-like receptor-4 levels and Helicobacter pylori Cag A status

BACKGROUND AND OBJECTIVE The aim of this study was to investigate the association between serum pepsinogens, serum gastrin, serum vascular endothelial growth factor, serum interleukin-1 Beta, serum toll-like receptor-4 levels and Helicobacter pylori Cag A status in patients with various gastric precancerous lesions. METHODS One hundred and sixty two consecutive patients with various gastric lesions [38 (23.5%) H. pylori positive chronic non-atrophic gastritis, 45 (27.8%) autoimmune gastritis, 42 intestinal metaplasia and 37 dysplasia] were enrolled into the study. Serum pepsinogen I and II, gastrin 17, vascular endothelial growth factor, interleukin-1 Beta, toll-like receptor-4 levels, H. pylori Cag A status were evaluated. RESULTS H. pylori was positive in 98 (60.5%) patients and 38 of these patients were Cag A positive. Serum pepsinogen level was significantly lower in patients with autoimmune atrophic gastritis compared to the patients with non-atrophic chronic gastritis (p<0.001), intestinal metaplasia (P<0.001) and dysplasia (P=0.002). Mean serum gastrin was 1209.6±268.48 pg/mL in patients with autoimmune atrophic gastritis and 234.95±184.018 pg/mL in patients with chronic non-atrophic gastritis. Mean toll-like receptor-4 level was 0.56±0.098 ng/mL in patient with dysplasia, and this value was higher compared to patients with chronic non-atrophic gastritis (P=0.007), autoimmune atrophic gastritis (P=0.003) and intestinal metaplasia (P=0.006). Interleukin-1 Beta level was significantly lower in patients with dysplasia compared to patients with chronic non-atrophic gastritis (P=0.034). CONCLUSIONS Serum pepsinogens, serum gastrin and H. pylori Cag A status are important tests in detecting gastric precancerous lesions. However, toll-like receptor-4 may be a sensitive test to differentiate the patients with dysplasia from the other precancerous gastric lesions. Non-invasive tests are sensitive in the diagnosis of gastric precancerous lesions.

Clinical Characteristics and Evaluation of Patients with Large Hiatal Hernia and Cameron Lesions

Objectives: Cameron lesions are located at the neck of large hiatal hernias, and are associated with anemia or overt gastrointestinal (GI) bleeding. The aim of this study was to investigate the clinical and endoscopic properties of patients with Cameron lesions. Methods: Eighteen patients were diagnosed as having large hiatal hernia and Cameron lesions. Patients with Cameron lesions (n = 18) were compared to patients with large hiatal hernias without Cameron lesions (n = 26), by means of presenting symptoms and endoscopic findings. Results: The mean age of patients with Cameron lesions was significantly higher than patients without Cameron lesions (71.1 ± 11.63 vs 56.7 ± 17.4 years, P = 0.005). The ratio of female patients with Cameron lesions was higher compared to patients with large hiatal hernia without Cameron lesions (14/18 [77.7%] vs 12/26 [46.1%], P = 0.00). While 12 of 18 patients with Cameron lesions had overt GI bleeding, none of the patients with large hiatal hernia without Cameron lesions had signs of GI bleeding. Fifteen of 18 patients had ulcers in the hernia sac and the others had linear erosions. There was no significant difference between patients with and without Cameron lesions by means of hemoglobin levels (11.1 ± 2.20 vs 12.2 ± 2.5 g/dL, P = 0.157). Conclusion: Most patients with large hiatal hernia and Cameron lesions presented with overt GI bleeding. Patients with Cameron lesions tend to be older females. In patients with anemia and GI bleeding, large hiatal hernia and Cameron erosions should also be considered.

The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors

Abstract Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p < 0.001) and red cell distribution width (16.11 ± 3.04 vs. 13.41 ± 0.95%, p < 0.001) were significantly higher in autoimmune gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.

Clonal analysis of the quasispecies of antiviral-resistant HBV genomes in patients with entecavir resistance during rescue treatment and successful treatment of entecavir resistance with tenofovir.

BACKGROUND Clonal analysis of quasispecies of resistant HBV genomes in patients with entecavir (ETV) resistance receiving lamivudine (3TC) plus adefovir (ADV) rescue therapy has never been performed. METHODS A sample of 10 patients with ETV resistance who were switched to 3TC+ADV treatment were analysed for changes in viral quasispecies. Serum samples at baseline, and at months 3 and 6 of 3TC+ADV treatment could be clonally analysed in 7 of 10 patients; 3-82 clones per sample (total 1,068 clones, mean 63) were sequenced. RESULTS 3TC+ADV therapy led to a modest decline in HBV DNA. Almost all clones had L180M and M204V 3TC resistance mutations before and during combination therapy. All clones had ≥1 of the S202G, T184F, T184A, T184L, T184I and M250V ETV resistance mutations. The percentages of detected clones bearing 3TC (rtL180M and rtM204V) and ETV mutations did not change with rescue 3TC+ADV therapy. In 7 of 8 patients with detectable HBV DNA (median 5.17 log(10) copies/ml) after a median 24 months of ADV therapy, HBV DNA became undetectable with 3TC plus tenofovir after 6 months of treatment. CONCLUSIONS In patients with ETV resistance tenofovir is effective. Clonal analysis data indicate no selection of specific HBV mutants during rescue 3TC+ADV.

Manometric assessment of esophageal motor function in patients with primary biliary cirrhosis

INTRODUCTION/AIM Primary biliary cirrhosis is associated with other autoimmune diseases including Sjögrens syndrome, and scleroderma. Esophageal dysmotility is well known in scleroderma, and Sjögrens syndrome. The aim of this study is to investigate whether any esophageal motor dysfunction exists in patients with primary biliary cirrhosis. METHOD The study was performed in 37 patients (36 women, mean age: 56.29 ± 10.01 years) who met diagnostic criteria for primary biliary cirrhosis. Thirty-seven functional dyspepsia patients, were also included as a control group. Patients entering the study were asked to complete a symptom questionnaire. Distal esophageal contraction amplitude, and lower esophageal sphincter resting pressure were assessed. RESULTS Manometric findings in primary biliary cirrhosis patients vs. controls were as follows: Median lower esophageal sphincter resting pressure (mmHg): (24 vs 20, p=0.033); median esophageal contraction amplitude (mmHg): (71 vs 56, p=0.050); mean lower esophageal sphincter relaxation duration (sc, x ± SD): (6.10 ± 1.18 vs 8.29 ± 1.92, p<0.001); and median lower esophageal sphincter relaxation (%) (96 vs 98, p=0.019); respectively. No significant differences were evident in median peak velocity (sc) (3.20 vs 3.02, p=0.778) between patients with primary biliary cirrhosis and the functional dyspepsia patients. Esophageal dysmotility was found in 17 (45.9%) primary biliary cirrhosis patients (non-specific esophageal motor disorder in ten patients, hypomotility of esophagus in five patients, nutcracker esophagus in one patient and hypertensive lower esophageal sphincter in one patient). CONCLUSION Esophageal dysmotility was detected in 45.9% of patients. The study suggests that subclinic esophageal dysmotility is frequent in patients with primary biliary cirrhosis.