Improvement of Work Productivity and Quality of Life with Anti-Tumor Necrosis Factor Treatment Used in Crohn's Disease in Routine Clinical Practice in Turkey.

BACKGROUND: Patients with Crohn's disease experience major deterioration in work productivity and quality of life. We aimed to provide the long-term effects of anti-tumor necrosis factor agents on work productivity and activity impairment and quality of life in patients with Crohn's disease using the Inflammatory Bowel Disease Questionnaire and the Short-Form Health Survey-36. METHODS: Patients with Crohn's disease and initiated an anti-tumor necrosis factor treatment were included and followed up for 12 months in this observational study. RESULTS: A total of 106 patients were included in this study, and 64.2% of the patients were males. Mean [± standard deviation] age was 36.8 [± 10.9] years. At baseline, mostly perianal fistulas [65.7%] were observed [n = 23]. Intestinal stenosis was detected in 34.9% of the patients [n = 37], and most of the stenosis was located in the ileum [70.6%] followed by the colon [20.6%]. Extraintestinal symp- toms were observed in 24 patients [22.6%]. Most frequent extraintestinal symptom was arthritis with 71.4% [n = 15]. Mean time from first symptom to initiation of anti-tumor necrosis factor treatment was 6.3 [± 5.0] years. Improvements in work productivity and activ- ity impairment scores throughout 12 months were -24.1% [P = .003] for work time missed, -18.0% [P = .006] for impairment at work, -8.5% [P = .160] for overall work impairment, and -17.0% [P < .001] for daily activity impairment. Similarly, significant improvements [P < .001] were detected in all components of the Inflammatory Bowel Disease Questionnaire when compared to baseline. Statistically sig- nificant improvements [P < .05] were detected for all components of Short-Form Health Survey-36 except for mental health [P = .095]. CONCLUSION: Our study indicates the significant improvement in work productivity and activity impairment and quality of life of patients with Crohn's disease who receive long-term anti-tumor necrosis factor treatment.

Differential diagnosis of Crohn's disease using antibodies to glycoprotein 2 and Saccharomyces cerevisiae.

BACKGROUND/AIMS: Glycoprotein 2 (GP2), the major autoantigen of Crohn's disease (CD)-specific pancreatic autoantibodies, is reportedly correlated with several characteristics of CD. We investigated this serological marker in Turkish patients with CD and assessed its utility in combination with anti-Saccharomyces cerevisiae antibodies (ASCAs) for differential diagnosis of CD. MATERIALS AND METHODS: A total of 60 patients with CD, 62 patients with ulcerative colitis (UC), and 46 healthy controls with a definite diagnosis who were similar in age and sex were enrolled in the study conducted from November 2011 to October 2012. ASCA and anti-GP2 levels were measured using commercially available kits. RESULTS: Anti-GP2 IgA and IgG levels were higher in patients with CD (25%) than in those with UC (5%) and controls (2%). The seroprevalence of anti-GP2 IgA was markedly higher than that of IgG in patients with CD in contrast to previous studies. The specificity and positive predictive value of seropositivity for both ASCA and anti-GP2 were 100%. ASCA IgA seropositivity was correlated with a complicated disease course and a history of surgery. There was no correlation between anti-GP2 seropositivity and disease location, disease behavior, or a history of surgery. CONCLUSION: The combination of ASCA and anti-GP2 may enable differentiation of CD from UC. As ASCA seropositivity is associated with a more complicated disease course, patients seropositive for ASCA at the initial diagnosis should undergo more intense therapy.

Comparison of the effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on intragastric pH in extensive metabolizer patients with gastroesophageal reflux disease.

BACKGROUND/AIMS: Studies on the therapeutic efficacy of proton pump inhibitors (PPIs) in patients with gastroesophageal reflux disease (GERD) have been recently published. In most of these studies, comparison of only two PPIs have been made. There are few studies on the comparison of four or more PPIs. We aimed to compare the acid inhibitory effects of esomeprazole 40 mg, rabeprazole 20 mg, lansoprazole 30 mg, and pantoprazole 40 mg on days 1 and 5 of treatment in patients with GERD, who were extensive metabolizers in regard to the CYP2C19 genotype. MATERIALS AND METHODS: Helicobacter pylori-negative with typical symptoms of GERD patients were randomly divided into four treatment groups. Efficacy analysis on days 1 and 5 were performed on the four groups which comprised 10 (esomeprazole), 11 (rabeprazole), 10 (lansoprazole), and 10 (pantoprazole) patients. RESULTS: On day 1 of PPI treatment, the mean percentage of time with intragastric Ph>4 were 54%, 58%, 60%, and 35% for the groups, respectively, and on day 5, these values were 67%, 60%, 68%, and 59%, respectively. Esomeprazole, rabeprazole, and lansoprazole were found to be superior to pantoprazole on the first day of treatment. CONCLUSION: Pantoprazole is a less potent proton pump inhibitor than the other PPIs tested on the first day of treatment. When the time needed to raise the intragatric pH to over 4 was evaluated, esomeprazole was found to have the most rapid action, followed by lansoprazole and rabeprazole.

The relationship between fibrosis level and blood neutrophil to lymphocyte ratio in inactive hepatitis B carriers.

AIM: Neutrophil-lymphocyte ratio (NLR) has been used as a simple, affordable, and easily accessible marker to predict prognosis in a variety of inflammatory and neoplastic diseases. However, there are few studies investigating their role in patients with hepatitis B. The aim of this study was to investigate the relationship between NLR and liver fibrosis in patients who were being followed as inactive hepatitis B carriers. MATERIALS AND METHODS: The study included 78 patients who were followed for 1 year as inactive hepatitis B carriers. Liver biopsy was performed and the fibrosis scores of the histological activity index were assessed according to the Metavir scoring system. The patients were divided into two groups on the basis of the fibrosis scores: those with a score below 2 and those with a score above 2. In both groups, demographic data such as sex, age, and BMI were similar. The NLR of patients was calculated from blood samples taken at the same time as the biopsy. RESULTS: Histopathologic analysis of 78 patients showed that 41 (53%) had fibrosis grade 0-1 and 37 (47%) patients had fibrosis grade greater than 2. According to the biopsy results, there were no cirrhotic patients. NLR was found to be statistically significantly lower in the group with fibrosis grade of at least 2 (1.51±0.61 vs. 1.79±0.64, P=0.043). Other biochemical and hematological data were found to be similar in both groups. No correlation was found between laboratory values and NLR. In addition, there was no correlation between NLR with histologic activity. Spearman correlation analysis showed a negative correlation between the fibrosis score and NLR (r=-0.279, P=0.013). CONCLUSION: In inactive hepatitis B carriers, the histological activity index and NLR were found to be correlated negatively. NLR can be used as a predictor of fibrosis in combination with other noninvasive markers.

Valsartan-induced acute pancreatitis.

Gastrointestinal toxicity is uncommon among patients treated with angiotensin II receptor antagonists. A 58-year-old man presented with nausea, vomiting and constant pain in the epigastrium that radiated to the flanks. He received treatment with valsartan (160 mg daily) for hypertension. The clinical, biochemical and radiological findings were compatible with a diagnosis of acute pancreatitis. After the patient achieved a clinical and biochemical recovery, the valsartan therapy was started again. Six weeks later, he returned to the hospital with an attack of pancreatitis. Subsequently, he returned with repeated attacks of pancreatitis twice, and the valsartan was discontinued. Ten months after the treatment, the patient had no complaints. When severe abdominal symptoms occur for no apparent reason during treatment with valsartan, a diagnosis of pancreatitis should be considered.

The relationship between resistin and ghrelin levels with fibrosis in nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease. It is generally accepted that insulin resistance is a pathophysiological factor in the development of NAFLD. In the present study, the aim was to determine the relationship between resistin and ghrelin levels, which were found to be closely related to insulin resistance and fibrosis scores in NAFLD. MATERIALS AND METHODS: A total of 40 (21 male, 19 female) NAFLD patients whose diagnosis was confirmed with biopsy and 40 (18 male, 22 female) healthy controls were included in the study. RESULTS: In the comparison of resistin and ghrelin levels, only resistin values were found to be significantly higher in NAFLD group while there was no significant difference in ghrelin values (respectively P < 0.05; P = 0.078). In according to the fibrosis groups there was no difference about fasting plasma glucose, insulin values, Homeostatic Measurement Assessment-Insulin Resistance measurements and also resistin and ghrelin levels. CONCLUSION: It has been understood that insulin resistance plays an important part in NAFLD. Larger studies are required that investigate the gene expression of hormones influencing insulin resistance, particularly resistin and ghrelin in order to determine their role in NAFLD.

Endoscopic submucosal dissection for colorectal laterally spreading tumors.

BACKGROUND/AIMS: Colorectal laterally spreading tumors are superficial tumors classified into two groups as granular (G-laterally spreading tumor) and non-granular (non-granular-laterally spreading tumor) types. In this study, we aimed to investigate the efficacy and feasibility of endoscopic submucosal dissection in the treatment of laterally spreading tumors. MATERIALS AND METHODS: Forty-four laterally spreading tumors in 40 patients were treated with endoscopic submucosal dissection at a tertiary referral hospital. Patient data were collected retrospectively. In this study, we evaluated tumor size, macroscopic type, lesion location, histology, curative resection, and complications. RESULTS: Of the 44 laterally spreading tumors excised by endoscopic submucosal dissection, 29 (65.9%) were G-laterally spreading tumor and 15 (34.1%) were non-granular-laterally spreading tumor. Most of the non-granular-laterally spreading tumors were localized in the right colon, while most G-laterally spreading tumors were localized in the left colon (p<0.001). There was also no difference between G-laterally spreading tumors (6/29) and non-granular-laterally spreading tumors (2/15) with regard to exhibiting malignant features (p=0.69). Although median size (40 mm vs. 27.5 mm) and procedure time (115 minutes vs. 60 minutes) for G-laterally spreading tumors were bigger and longer respectively, procedure time per cm2 was not different (8.9 minutes vs. 8.2 minutes) between the two groups. Curative resection rates for laterally spreading tumors were quite high (95.5%), while en bloc resection rates were low (77.3%). The rates of endoscopic submucosal dissection-related complications such as perforation, major and minor bleeding were low (4.5%, 2.3%, 6.8%, respectively). CONCLUSION: Endoscopic submucosal dissection is an effective and safe therapeutic option with high curative rates for early-stage malignant and pre-malignant laterally spreading tumors not having an absolute indication for surgery, regardless of the lesion type and size.

Nonresponsive celiac disease due to Strongyloides stercoralis infestation.

Celiac disease (CD) is treated by eliminating all gluten from the diet. A 49-year-old man with CD was admitted to our clinic with complaints of recurrent diarrhea and abdominal pain despite strict adherence to a gluten-free diet. The duodenum was seen to be edematous on gastroduodenoscopic examination. Histological examination of the biopsy specimen taken from the duodenum showed multiple round shaped Strongyloides stercoralis (S. stercoralis) larvae within the crypts. He was successfully treated with albendazole. This case emphasizes the importance of duodenal biopsy in CD. To our knowledge, this is the first case in the literature showing CD and S. stercoralis together.

Severe jaundice due to coexistence of Dubin-Johnson syndrome and hereditary spherocytosis: a case report.

Dubin-Johnson syndrome is a chronic, benign, intermittent jaundice, mostly of conjugated hyperbilirubinemia. The level of bilirubin is not expected to be more than 20 mg/dl in this syndrome. In this article, we report a patient who was evaluated for hyperbilirubinemia and liver function test abnormalities and diagnosed with Dubin-Johnson syndrome coexisting with hereditary spherocytosis. We suggest that other diseases should be investigated if patients with Dubin-Johnson syndrome present with severe hyperbilirubinemia. Dubin-Johnson syndrome accompanied by hemolytic diseases might also have high coproporphyrin levels (as in Rotor's syndrome) than expected in pure Dubin-Johnson syndrome.

Endoscopic submucosal dissection for premalignant lesions and noninvasive early gastrointestinal cancers.

AIM: To investigate the indication, feasibility, safety, and clinical utility of endoscopic submucosal dissection (ESD) in the management of various gastrointestinal pathologies. METHODS: The medical records of 60 consecutive patients (34 female, 26 male) who underwent ESD at the gastroenterology department of Kocaeli University from 2006-2010 were examined. Patients selected for ESD had premalignant lesions or non-invasive early cancers of the gastrointestinal tract and had endoscopic and histological diagnoses. Early cancers were considered to be confined to the submucosa, with no lymph node involvement by means of computed tomography and endosonography. RESULTS: Sixty ESD procedures were performed. The indications were epithelial lesions (n = 39) (33/39 adenoma with high grade dysplasia, 6/39 adenoma with low grade dysplasia), neuroendocrine tumor (n = 7), cancer (n = 7) (5/7 early colorectal cancer, 2/7 early gastric cancer), granular cell tumor (n = 3), gastrointestinal stromal tumor (n = 2), and leiomyoma (n = 2). En bloc and piecemeal resection rates were 91.6% (55/60) and 8.3% (5/60), respectively. Complete and incomplete resection rates were 96.6% (58/60) and 3.3% (2/60), respectively. Complications were major bleeding [n = 3 (5%)] and perforations [n = 5 (8.3%)] (4 colon, 1 stomach). Two patients with colonic perforations and two patients with submucosal lymphatic and microvasculature invasion (1 gastric carcinoid tumor, 1 colonic adenocarcinoma) were referred to surgery. During a mean follow-up of 12 mo, 1 patient with adenoma with high grade dysplasia underwent a second ESD procedure to resect a local recurrence. CONCLUSION: ESD is a feasible and safe method for treatment of premalignant lesions and early malignant gastrointestinal epithelial and subepithelial lesions. Successful en bloc and complete resection of lesions yield high cure rates with low recurrence.

Frequency and mutation patterns of resistance in patients with chronic hepatitis B infection treated with nucleos(t)ide analogs in add-on and switch strategies.

BACKGROUND: Treatment for chronic hepatitis B (CHB) has improved over the last 10 years mainly due to the development of effective oral antiviral agents [nucleoside/nucleotide analogs (NUCs)]. OBJECTIVES: The aim of the present study is to identify the frequency and major patterns of resistance to the hepatitis B virus (HBV) in a Turkish population of CHB patients treated with NUCs using add-on and switch therapy strategies. PATIENTS AND METHODS: The investigation involved a total of 194 patients (88 were treated using add-on therapy, and 106 were treated using switch therapy). We analyzed the HBV polymerase gene by amplification and direct sequencing procedures. RESULTS: Primary drug-resistance mutations were detected in 84 patients (43%; 42 in add-on therapy, and 42 in switch therapy) taking lamivudine (LAM), 10 patients (5%; 6 in add-on therapy, and 4 in switch therapy) taking entecavir (ETV), and 16 patients (8%; 8 in add-on therapy, and 8 in switch therapy) taking adefovir (ADV). The most common LAM and ETV resistance mutations were rtM204I/V, rtL180M and rtT184A/I/S, respectively, while rtA181T/V and rtN236T substitutions were the most frequently observed ADV resistance mutations. CONCLUSIONS: Patients with CHB who developed NUC resistance were managed using 2 different rescue strategies. The frequency and mutation pattern of resistance were similar in patients treated with add-on and switch strategies. These findings may be helpful in the management of rescue strategies in LAM-resistant patients.

Thrombophilic Risk Factors in Patients With Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) patients have an increased risk for thromboembolism. The aim of this study was to assess the presence of thrombophilic risk factors in IBD patients and to assess the associations of these factors with disease activity. METHODS: Forty-eight patients with IBD (24 ulcerative colitis, 24 Crohn's disease) and 40 matched healthy control individuals were enrolled. In addition to routine biochemical analysis, fasting blood samples were studied for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, protein-C, protein-S, antithrombin III, factor VII, factor VIII, D-dimer, vitamin B12, folic acid and homocysteine. RESULTS: Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, D-dimer and the number of platelets were significantly higher in patients with IBD. When compared to control group, in patients with Crohn's disease serum homocystein levels were significantly higher (p = 0.025) while serum folic acid levels were significantly lower (p < 0.019). Levels of fibrinogen, D-dimer, protein C, factor VIII, total homocystein and the number of platelets were found to be significantly higher in Crohn's disease patients who were in active period of the disease. CONCLUSIONS: Thrombophilic defects are multifactorial and might be frequently seen in IBD patients. They might contribute to thrombotic complications of this disease.

Erythema Annulare Centrifugum: A Rare Skin Finding of Autoimmune Hepatitis.

Erythema annulare centrifugum is characterized by dermal perivascular lymphocytic infiltrates. It is often associated with infections, autoimmune or neoplastic diseases but in most cases the cause is unexplained. A case of erythema annulare centrifugum related to autoimmune hepatitis in a 24-year-old woman is described in this case report. Clinical response of the autoimmune hepatitis to a combination therapy with corticosteroids and azothiopurine was achieved. Although partially regressed for the first 12 months of theraphy, the skin lesions did not disappear completely. However, after 18 months of continious treatment there was no skin lesion.

The prevalence of CYP2C19 mutations in Turkish patients with dyspepsia.

BACKGROUND/AIMS: We aimed to determine the distribution of cytochrome P450 2C19 (CYP2C19) genotype frequencies in Turkish patients with dyspepsia. METHODS: CYP2C19 genotype was determined in 100 Turkish patients with dyspepsia. DNA of the patients was isolated from whole blood and genotypes were detected by specific probes in real-time polymerase chain reaction (PCR). RESULTS: The frequencies of heterozygous CYP2C19*2 and CYP2C19*3 genotypes were 13% and 1% in dyspeptic patients, respectively. Homozygous mutant CYP2C19*2 was detected at a rate of only 1% in the study population, and homozygous mutant genotype of CYP2C19*3 was not found. The frequencies of homozygous CYP2C19*2 and CYP2C19*3 genotypes were 86% and 99% in dyspeptic Turkish patients, respectively. CONCLUSIONS: This is the first study investigating CYP2C19 polymorphism in dyspeptic Turkish patients. Our investigation revealed that the most common CYP2C19 genotype was wild type CYP2C19 in dyspeptic Turkish patients. Dyspeptic Turkish patients are extensive metabolizers for proton pump inhibitors. This finding might have impact on the clinical consequences for the treatment strategies in dyspepsia.

[Entecavir resistance in entecavir naive lamivudine treated chronic hepatitis B patients]. / Lamivudin tedavisi uygulanmis ve entekavir naif kronik hepatit B'li hastalarda entekavir ilaç direnci.

Approved hepatitis B virus (HBV) therapies include interferon-alpha and nucleos(t)ide analogues. Lamivudine (LVD) is a nucleoside analogue and following long term LVD therapy, resistance emerges in a significant number of patients. Entecavir (ETV) is a novel deoxyguanosine analogue with potent activity against HBV in chronically infected patients. ETV is highly efficacious in treating nucleoside naive and LVD refractory patients. The aim of the present study was to determine the prevalence of ETV drug resistance in LVD treated/ETV naive (study group) and in untreated naive (control group) patients with chronic B hepatitis. DNA sequencing was applied to 80.-250. amino acid positions on HBV polymerase gene to investigate the ETV resistance and also HBV genotype and HBV polymerase gene overlapped S-gene segment mutations. Primary LVD and ETV drug resistance were detected in 37 (42.6%) and 4 (4.5%) of 87 patients, respectively in the study group. rtT184A, rtT1841 and rtT1845 mutations were found related to primary ETV resistance. In these patients also rtL180M and rtQ215S mutations were detected as compensatory mutations and YVDD and YIDD variants were observed at the 204. amino acid codon position. None of the patients in the control group had LVD or ETV resistance. Two of the patients in the study group had mutations at the positions sG145R and sC137G in the overlapped S-gene segment. However, mutations at the overlapped S-gene segment were not affected by the mutations associated with ETV resistance. All of the patients in the study and the control group were of HBV genotype D. The results obtained from this study may guide the treatment choices with ETV in chronic HBV patients treated with LVD and developed resistance to LVD.