Eyvind J. Paulssen

The impact of body mass index and Helicobacter pylori infection on gastro-oesophageal reflux symptoms: A population-based study in Northern Norway

Objective. Increased body mass index (BMI) has been proposed as a risk factor for gastro-oesophageal reflux symptoms. The aim of this study was to evaluate the effect of BMI and Helicobacter pylori on reflux symptoms in an adult population. Material and methods. For this cross-sectional, population-based study from Bodø and Sørreisa communities in Northern Norway, a total of 3927 adults were invited to complete a questionnaire on gastrointestinal symptoms and to provide stool samples for the assessment of H. pylori. Reflux symptoms were considered present when a reflux syndrome score was ≥2 according to the Gastrointestinal Symptom Rating Scale (GSRS). Results. The response rate was 44.2%, and 44.7% of the respondents were male. Age-adjusted prevalences were: for overweight, 35.6% (95% CI (32.4%; 38.8%)); for obesity, 10.0% (8.4%; 11.6%); for H. pylori: 21.2% (19.1%; 23.9%) and for reflux symptoms: 21.7% (19.5%; 23.9%). In the logistic regression analyses, H. pylori and smoking were not risk factors for reflux symptoms, whereas male gender (OR 4.78 (95%CI (1.88; 12.1)), age (1.01 (1.00; 1.03)) and overweight (1.51 (1.14; 2.00)) were. When stratified by gender, overweight and age were independent risk factors for reflux symptoms in females only, whereas H. pylori infection was protective against such symptoms in men. Models including these parameters could only explain 3% of the variations in reflux symptoms. Conclusions. BMI is an independent risk factor for gastro-oesophageal reflux symptoms among healthy female adults, but contributes only to a minor part of the variation in these symptoms. H. pylori is protective against reflux symptoms in men.

Normalization of mucosal cytokine gene expression levels predicts long-term remission after discontinuation of anti-TNF therapy in Crohn's disease

Abstract Objective. To investigate mucosal cytokine gene expression levels in healed mucosa after anti-tumor necrosis factor (TNF) therapy in patients with Crohns disease (CD) as possible risk factors for relapse after discontinuation of therapy. Design. Thirty-seven CD patients treated with anti-TNF agents until complete mucosal healing, documented by endoscopy, discontinued anti-TNF treatment and entered a follow-up study. Levels of mRNA expression of interleukin (IL)17A (IL17A), IL23, interferon-gamma (IFNG), TNF-alpha (TNF), IL10 and Forkhead Box P3 (FOXP3) were measured in biopsies from healed mucosa and analyzed as possible risk factors of relapse. Mucosal cytokine transcript levels from patients without CD served as controls. Results. Patients were followed after therapy withdrawal until relapse. Median time to relapse was 20 and 68 weeks for patients with elevated and normalized IL17A and TNF expression levels, respectively (p = 0.02 for IL17A and p = 0.003 for TNF, log-rank). Expression levels of TNF, IL17A and FOXP3 were significantly higher in patients who relapsed before 26 weeks than in those who did not relapse, and also higher in patients with relapse before week 52 versus non-relapsers. Elevated expression levels of TNF and IL17A in healed mucosa significantly increased the risk of relapse (HR = 3.4, p = 0.03, sensitivity 80%, specificity 38% and HR = 4.1, p = 0.008, sensitivity 81%, specificity 61%, respectively). Conclusions. Normalization of mucosal gene expression of cytokines after anti-TNF therapy does not occur in all patients with healed mucosa as judged by endoscopy. Normalization of TNF and/or IL17A expression predicts long-term remission.

Accuracy of a Monoclonal Antibody-based Stool Antigen Test in the Diagnosis of Helicobacter pylori Infection

Background: Recent availability of tests for Helicobacter pylori antigens in stool samples has provided potentially useful tools for epidemiological studies and clinical settings. The aim of this study was to evaluate a monoclonal antibody-based H. pylori antigen stool test in the primary diagnosis of H. pylori infection, and to study the test performance after patients were treated with lanzoprazole, and after eradication therapy. Methods: The study included 122 dyspeptic patients. At gastroscopy, biopsy specimens were obtained for culture and histology. Stool antigen and [[Formula: See Text]C]-urea breath tests were performed concurrently. Positive culture alone or a positive [[Formula: See Text]C]-urea breath test in combination with positive histology defined the reference standard. Forty-three Hp +ve patients were treated with lanzoprazole for 2 to 4 weeks, and stool antigen tests were performed on days 1 and 7 post-treatment. After eradication therapy, 32 patients were re-examined for H. pylori infection. Results: Prevalence of H. pylori was 44.3%. Sensitivity and specificity for the stool antigen test in the primary diagnosis of H. pylori infection were 98% and 94%, with positive and negative likelihood ratios of 16.7 and 0.02, respectively. All patients had positive stool tests immediately after lanzoprazole treatment, whereas 2 patients had negative stool tests after 7 days. Triple therapy rendered all patients stool test negative. Conclusions: The monoclonal antibody-based stool antigen test is an accurate tool in the primary diagnosis of H. pylori infection and after eradication therapy. Lanzoprazole treatment does not influence the clinical performance of the test.

Changes in the prevalence of dyspepsia and Helicobacter pylori infection after 17 years: the Sørreisa gastrointestinal disorder study.

Dyspepsia and Helicobacter pylori infection are two important public health issues in the field of gastroenterology, generating high expenditures in diagnosis and treatment. A causal relationship between H. pylori and dyspepsia is still debated. The aim of this study was to address changes in the prevalence of, and association between, dyspepsia and H. pylori infection in a general population. The study took place in the municipality of Sørreisa in Northern Norway. Data were collected in 1987 and 2004. The study included questionnaires on gastrointestinal disorders and risk factors, as well as H. pylori assessment. The prevalence of dyspepsia in 2004 was 31.9% in men and 31.7% in women (compared with 30.7 and 26.3% in 1987). In 2004, the prevalence of H. pylori infection in men with/without dyspepsia was 20.3/26.7% (compared with 47.0/32.7% in 1987), whereas the prevalence of H. pylori infection in women with/without dyspepsia was 31.3/20.8% (compared with 50.0/40.7% in 1987). Since 1987, the prevalence of H. pylori has decreased independently of dyspepsia, most pronounced in the younger age groups, thus indicating a cohort effect. Our findings of a decreasing prevalence of H. pylori, a persistently high prevalence of dyspepsia, and an uneven distribution of H. pylori infection with regard to dyspepsia in men and women, question the understanding of a causal relationship between dyspepsia and H. pylori.

The effect of adalimumab for induction of endoscopic healing and normalization of mucosal cytokine gene expression in Crohn's disease

Abstract Objective. To investigate the effects of adalimumab on the induction of complete endoscopic healing and normalization of mucosal cytokine gene expression in patients with active Crohns disease. Material and methods. A prospective, single-center study including 77 patients. All were examined by endoscopy before initiation of adalimumab induction therapy with a minimum of six adalimumab injections. Patients were treated until documentation of complete endoscopic healing. Biopsies for measurements of mRNA expression levels of interleukin(IL)-17A (IL17A), IL23, interferon-gamma (IFNG), tumor necrosis factor-alpha (TNF), IL10 and Forkhead Box P3 (FOXP3), as well as for immunohistochemistry (IHC) were sampled at pre- and post-treatment endoscopy, and from 17 control patients. Results. Complete endoscopic healing was achieved in 27.3% after 10 weeks of treatment, documented by endoscopy at week 12. Cumulative endoscopic healing after 52 weeks was 44.2%. Complete endoscopic healing led to a significant reduction in mRNA expression levels for all cytokines except IL10. Elevated expression of TNF and IL-17A persisted in 52% and 76%, respectively, of patients with complete endoscopic remission. Pre-treatment cytokine gene expression levels did not predict response to adalimumab therapy. Conclusions: Adalimumab induces accumulated complete endoscopic healing in 44% of patients after 52 weeks of therapy. Normalization of mucosal gene expression of cytokines does not occur in all patients with endoscopy-verified healed mucosa. Inclusion of normalized mucosal cytokine expression into the concept of mucosal healing could have an impact on long-term clinical outcome.

Prevalence, comorbidity, and risk factors for functional bowel symptoms: a population-based survey in Northern Norway

Abstract Objective. To assess the occurrence of functional bowel (FB) symptoms in Northern Norway, and to describe gender differences, comorbidity, and association to risk factors, including Helicobacter pylori infection. Materials and methods. Adult subjects (18–85 years) from the communities Bodø and Sørreisa were invited to complete a questionnaire on gastrointestinal symptoms, and to provide stool samples for assessment of H. pylori. Results. Of 3927 invited subjects, 1731 (44.1%) responded to the questionnaire and 1416 (36.0%) provided stool samples. Functional bowel symptoms were found in 25%, somewhat more frequent in females (28.6%). Symptom pattern differed between genders only with regard to constipation. Presence of FB symptoms was significantly associated with gastroesophageal reflux symptoms, headache, dizziness, palpitations, sleep disturbances, and musculoskeletal symptoms. Psychometric traits were also more prevalent: feeling of low coping ability, feeling depressed, feeling of time pressure, and a low self-evaluation of health. In a multivariate regression model, factors that influenced the reporting FB symptoms were male gender (OR 0.71, 95% CI (0.52; 0.96)), age 50–69 years or ≥70 years (OR 0.49 (0.30; 0.80) and 0.40 (0.21; 0.79)), obesity (OR 1.61 (1.05; 2.47)), NSAID use (OR 2.50 (1.63; 3.83)), and previous abdominal surgery (OR 1.54 (1.05; 2.26)). The presence of H. pylori was not associated with FB symptoms. Conclusions. Functional bowel symptoms are prevalent, but our findings may be prone to self-selection bias. FB symptoms carry a significant burden of comorbidity. Female gender and low age are known risk factors for FB symptoms, whereas NSAID use as a risk factor deserves further clarification.

A rapid chemokine response of macrophage inflammatory protein (MIP)‐1α, MIP‐1β and the regulated on activation, normal T expressed and secreted chemokine is associated with a sustained virological response in the treatment of chronic hepatitis C

The role of chemokines in chronic hepatitis C virus (HCV) infection is not fully understood. The present study aimed to characterize the baseline serum concentrations and the initial β-chemokine response to treatment with interferon-α and ribavirin with respect to the final clinical outcome of virological response to treatment. Serum concentrations of alanine aminotransferase (ALT) and of the CC subfamily chemokines [macrophage inflammatory protein (MIP)-1α, MIP-1β, monocyte chemoattractant protein (MCP)-1 and the regulated on activation, normal T expressed and secreted (RANTES) chemokine] were measured in patients with chronic HCV infection and in healthy individuals. Necroinflammation and fibrosis were scored in liver biopsies. Treatment outcomes were classified as with or without a sustained virological response after a full-course treatment according to the genotypes. The main treatment group consisted of 72 patients with chronic hepatitis C, whereas 24-h blood samples were available for 42 patients. Increased baseline levels of all CC chemokines were found in the two responder groups compared to the healthy controls, although significant levels were reached only for MIP-1α and MCP-1. No correlation was observed between chemokine levels and serum ALT levels, any histological necroinflammatory parameters, or the fibrosis grade. After 24 h of treatment, increases in MIP-1α, MIP-1β and RANTES levels were exclusively observed in the group with sustained virological response. MCP-1 was also significantly increased after 24 h in both responder groups, although no differences were observed between the two responder groups. In conclusion, an early MIP-1α, MIP-1β, and RANTES response may predict a sustained response to virological treatment.

Impact of observer variability on the usefulness of endoscopic images for the documentation of upper gastrointestinal endoscopy

Objective. Endoscopy is an observer-dependent diagnostic method, which, until recently, has lacked precise guidelines for written reports. There is an increasing demand for improvement in endoscopy records, which may necessitate the supplementation of image documentation. The aim of this study was to estimate interobserver as well as intra-observer variability in the assessment of images from gastroscopy. Material and methods. We designed an Internet interface presenting endoscopy images, accompanied by a multiple-choice questionnaire for assessing pathology in the images. Ten images from the distal oesophagus and 10 images from the pyloric antrum were chosen. In order to study interobserver variability, physicians with varying endoscopy experience were invited to complete the questionnaire. The physicians were re-invited 5 months later to assess the same images again, this time in order to assess intra-observer variability. Kappa statistics were used for analysis of agreement. Results. Initially, 13 of 20 invited physicians responded. Interobserver agreement varied between poor (κ<0.2) and moderate (0.4<κ<0.6). In the second part of the study, 10 of 11 invited physicians responded. Intra-observer agreement varied between moderate (0.4<κ<0.6) and good (0.6<κ<0.8). A higher level of experience does not imply either better interobserver or better intra-observer agreement. Images of concise endoscopy findings, such as the presence of an ulcer, resulted in better agreement than did the assessment of images of less definable findings. Conclusion. The variability in the interpretation of endoscopy images is large. We therefore believe that systematic inclusion of a set of images into endoscopy reports will improve their quality.

The All-Age Prevalence of Helicobacter pylori Infection and Potential Transmission Routes. A Population-Based Study.

Previous research on H. pylori epidemiology has mostly focused on adult populations. We have aimed to study H. pylori prevalence in all age groups including children and adolescents and to identify potential routes of transmission.

Normalization of mucosal tumor necrosis factor-α: A new criterion for discontinuing infliximab therapy in ulcerative colitis.

BACKGROUND Biological agents such as anti-tumor necrosis factor (TNF) induce remission in ulcerative colitis. There is however no consensus regarding the discontinuation of this treatment. AIM The aim of this study is to assess whether clinical parameters and mucosal cytokine mRNAs in healed colonic mucosa can predict long-term remission in ulcerative colitis following discontinuation of infliximab (IFX) therapy. METHODS The prospective Tromsø Inflammatory Bowel Disease (IBD) Study is based on an intensified induction treatment algorithm with IFX to achieve disease remission. Following clinical and endoscopic remission, IFX treatment was discontinued, and follow-up until relapse was performed. Patients who achieved clinical and endoscopic remission following an induction course of IFX were included. Expression levels of TNF alpha (TNF), interferon gamma (IFNG), interleukin (IL) 6 (IL6), IL17A, IL23, and transforming growth factor beta (TGFB) were quantified by real-time PCR in mucosal biopsies obtained at colonoscopy. Remission was defined as Ulcerative Colitis Disease Activity Index (UCDAI) below 3, and an endoscopic sub-score of 0-1. Relapse was defined as UCDAI score >3 and endoscopic sub-score >1. Mucosal cytokine transcript levels from 20 non-IBD patients with a normal colonoscopy served as control group. RESULTS Of the 45 patients included, twenty patients (44%) had normalized levels of mucosal TNF expression at the time of mucosal healing, whereas 35 of 42 (83%) had normalized IL17A expression levels, and 31 of 36 (86%) had normalized IFNG expression levels. The median time to relapse was 8months (range 4-12). Normalization of TNF gene expression predicted 20months (1-39) relapse-free survival after withdrawal of IFX compared to 5months (3-7) in the group with elevated TNF expression. Mucosal expression levels of IL17A, IL23, IFNG, TGFB, IL6 did not predict long-term remission (>12months) CONCLUSION Normalization of mucosal TNF predicts long-term remission after discontinuation of IFX.