Meta-analyses: Does long-term PPI use increase the risk of gastric premalignant lesions?

Background: Proton pump inhibitors (PPIs) are the most effective agents available for reducing acid secretion. They are used for medical treatment of various acid-related disorders. PPIs are used extensively and for extended periods of time in gastroesophageal reflux disease (GERD). A troublesome issue regarding maintenance therapy has been the propensity of PPI-treated patients to develop chronic atrophic gastritis while on therapy that could theoretically lead to an increased incidence of gastric cancer. In addition, animal studies have raised concern for development of enterochromaffin-like cell hyperplasia and carcinoid tumors in the stomachs of mice receiving high dose PPIs. Current literature does not provide a clear-cut conclusion on the subject and the reports are sometimes contradictory. Therefore, this study is a systematic review of the available literature to address the safety of long-term PPI use and its relation to the development of malignant/premalignant gastric lesions. Methods: A literature search of biomedical databases was performed. The reference lists of retrieved articles were reviewed to further identify relevant trials. We hand-searched the abstracts of the American Digestive Disease Week (DDW) and the United European Gastroenterology Week (UEGW) from 1995 to 2013. Only randomized clinical trials (RCTs) that used PPIs as the primary treatment for at least six month versus no treatment, placebo, antacid or anti-reflux surgery (ARS) were included. Two reviewers independently extracted the data. Discrepancies in the interpretation were resolved by consensus. All analyses of outcomes were based on the intention-to-treat principle. We performed statistical analysis using Review Manager software. The effect measure of choice was relative risk (RR) for dichotomous data. Results: Six RCTs with a total of 785 patients met the inclusion criteria. Two multicenter RCTs compared Esomeprazole with placebo. One RCT compared omeprazole with ARS. Two RCTs compared omeprazole with ranitidine and one RCT compared lansoprazole with ranitidine. Four of the included RCTs had moderate risk of bias and two had low risk of bias. The number of patients with increased corporal atrophy score, intestinal metaplasia score and chronic antral inflammation did not statistically differ between the PPI maintenance group and controls. Similar results were found when ECL-cell hyperplasia was assessed between the groups. ConclusionS: Maintenance PPIs did not have an association with increased gastric atrophic changes or ECL-cell hyperplasia for at least three years in RCTs

Impact of immunosuppressive treatment on liver fibrosis in autoimmune hepatitis

The impact of treatment on progression of fibrosis in autoimmune hepatitis (AIH) is unknown. We assessed the changes in liver fibrosis before and after treatment among these patients. Nineteen AIH patients who had paired liver biopsies were studied. Of these, seven had been treated with 6 months of cyclosporine A and the rest with 6 months of prednisolone for induction of remission. Thereafter all had been maintained on azathioprine. Biopsy specimens before and after treatment were reviewed by one pathologist and scored by the Ishak method. Mean fibrosis stages before and after treatment were compared. Also, factors predicting significant fibrosis (stage �3) and cirrhosis (stage �5) at presentation were assessed. Mean interval between biopsies was 3.38 years. Mean fibrosis stage decreased from 4.53 to 2.16 following treatment (P < 0.001). Mean decrement in inflammatory grade was 8 scores (range, 4-10) in patients in whom fibrosis improved, and 2 scores (range, 0-4) in patients in whom fibrosis did not decrease after treatment (P < 0.001). ALT-to-platelet ratio was the best predictor of significant fibrosis and also cirrhosis. Fibrosis commonly improves after immunosuppressive treatment in AIH. ALT-to-platelet ratio can predict accurately the presence of significant fibrosis and cirrhosis in AIH. © 2005 Springer Science+Business Media, Inc

Diagnostic Accuracy of Age and Alarm Symptoms for Upper GI Malignancy in Patients with Dyspepsia in a GI Clinic: A 7-Year Cross-Sectional Study

<div><h3>Objectives</h3><p>We investigated whether using demographic characteristics and alarm symptoms can accurately predict cancer in patients with dyspepsia in Iran, where upper GI cancers and <em>H. pylori</em> infection are common.</p> <h3>Methods</h3><p>All consecutive patients referred to a tertiary gastroenterology clinic in Tehran, Iran, from 2002 to 2009 were invited to participate in this study. Each patient completed a standard questionnaire and underwent upper gastrointestinal endoscopy. Alarm symptoms included in the questionnaire were weight loss, dysphagia, GI bleeding, and persistent vomiting. We used logistic regression models to estimate the diagnostic value of each variable in combination with other ones, and to develop a risk-prediction model.</p> <h3>Results</h3><p>A total of 2,847 patients with dyspepsia participated in this study, of whom 87 (3.1%) had upper GI malignancy. Patients reporting at least one of the alarm symptoms constituted 66.7% of cancer patients compared to 38.9% in patients without cancer (p<0.001). Esophageal or gastric cancers in patients with dyspepsia was associated with older age, being male, and symptoms of weight loss and vomiting. Each single predictor had low sensitivity and specificity. Using a combination of age, alarm symptoms, and smoking, we built a risk-prediction model that distinguished between high-risk and low-risk individuals with an area under the ROC curve of 0.85 and acceptable calibration.</p> <h3>Conclusions</h3><p>None of the predictors demonstrated high diagnostic accuracy. While our risk-prediction model had reasonable accuracy, some cancer cases would have remained undiagnosed. Therefore, where available, low cost endoscopy may be preferable for dyspeptic older patient or those with history of weight loss.</p> </div

Crohn's Disease and Early Exposure to Domestic Refrigeration

Environmental risk factors playing a causative role in Crohn's Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood.Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01-4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD.This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood

Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common causes of elevated liver enzymes in the general population. NASH and to some extent NAFLD have been associated with increased liver-related and all-cause mortality. No effective treatment is yet available. Recent reports have shown that the use of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) in patients with elevated plasma aminotransferases may result in normalisation of these liver enzymes. Whether this is a consistent effect or whether it can lead to improved clinical outcomes beyond normalisation of abnormal liver enzymes is not clear. To assess the beneficial and harmful effects of statins (that is, lovastatin, atorvastatin, simvastatin, pravastatin, rosuvastatin, and fluvastatin) on all-cause and liver-related mortality, adverse events, and histological, biochemical, and imaging responses in patients with NAFLD or NASH. We performed a computerised literature search in the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded up to March 2013. We did fully recursive searches from the reference lists of all retrieved relevant publications to ensure a complete and comprehensive search of the published literature. We did not apply any restrictions regarding language of publication or publication date. All randomised clinical trials using statins as the primary treatment for NAFLD or NASH versus no treatment, placebo, or other hypolipidaemic agents. Data were extracted, and risk of bias of each trial was assessed independently by two or more review authors. Meta-analyses were performed whenever possible. Review Manager 5.2 was used. When the described search method was used and the eligibility criteria of the search results were applied, 653 records were found. Only two of these were randomised clinical trials that were considered eligible for inclusion. We assessed both trials as trials with high risk of bias. One of the trials was a pilot trial in which 16 participants with biopsy-proven NASH were randomised to receive simvastatin 40 mg (n = 10) or placebo (n = 6) once daily for 12 months. No statistically significant improvement in the aminotransferase level was seen in the simvastatin group compared with the placebo group. Liver histology was not significantly affected by simvastatin.The other trial had three arms. The trial compared atorvastatin 20 mg daily (n = 63) versus fenofibrate 200 mg daily (n = 62) versus a group treated with a combination of the two interventions (n = 61). There were no statistically significant differences between any of the three intervention groups regarding the week 54 mean activity levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. The triglyceride levels seemed higher in the fenofibrate group compared with the atorvastatin group. Liver histology was not assessed in this trial. The presence of biochemical and ultrasonographic evidence of NAFLD seemed to be higher in the fenofibrate group compared with the atorvastatin group (58 versus 33). Three patients discontinued treatment due to myalgia and elevated serum creatine kinase activity; one from the atorvastatin group and two from the combination group. Another patient from the atorvastatin group discontinued treatment due to alanine aminotransferase activity that was over three times the upper normal limit.No data for all-cause mortality and hepatic-related mortality were reported in the included trials. Based on the findings of this review, which included two trials with high risk of bias and a small numbers of participants, it seems possible that statins may improve serum aminotransferase levels as well as ultrasound findings. Neither of the trials reported on possible histological changes, liver-related morbidity or mortality. Trials with larger sample sizes and low risk of bias are necessary before we may suggest statins as an effective treatment for patients with NASH. However, as statins can improve the adverse outcomes of other conditions commonly associated with NASH (for example, hyperlipidaemia, diabetes mellitus, metabolic syndrome), their use in patients with non-alcoholic steatohepatitis may be justified

Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Tabriz, Iran

&quot;nBackground: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal problems in the west while different reports indicate an increase in the prevalence in Iran. The aim of this study was to estimate the preva&amp;shy;lence and clinical spectrum of GERD in staff of a referral hospital and evaluate the risk factors.&quot;nMethods: This cross-sectional study using a modified Mayo clinic questionnaire was performed on staff of Imam Hospi&amp;shy;tal, Tabriz, Iran on a pilot of 50 subjects, and a randomly selected group consisted of 522 subjects in the year 2005. GERD symptoms were defined as at least weekly heartburn and/or acid regurgitation during the past year.&quot;nResults: Response rate was 95%. Mean age of responders was 40.02&amp;plusmn;10.72 yr. The prevalence of recurrent heart&amp;shy;burn and/or acid regurgitation experienced at least weekly and monthly was 26.8% and 34.1%, respectively. They were not related to age and gender. The severity of symptoms was mainly reported of a mild to moderate degree. 45% of the cases reported at least one of the atypical symptoms. There was no relation between marriage status and preva&amp;shy;lence of GERD. On the other hand, GERD was less common among cases with no family history of upper gas&amp;shy;trointestinal disease. The prevalence of frequent GERD was more common among medical staff. Increased BMI (but no recent weight gain or lose) was associated with higher prevalence of GERD symptoms only in women. In&amp;shy;terestingly 33% of our population had a history of using antacid or PPIs which was more among cases with frequent GERD symptoms.&quot;nConclusion: This study revealed a high prevalence of frequent GERD symptoms in a selected population of Tabriz. Atypi&amp;shy;cal symptoms should be considered in this area. &amp;nbsp