The contribution of metabolic risk factors to cardiovascular mortality in Golestan cohort study: Population attributable fraction estimation.

Background: Cardiovascular diseases (CVDs) are the leading causes of global mortality and disability. Several studies demonstrated that metabolic risk factors increase cardiovascular mortality. The aim of this study is to examine CVDs deaths and population attributable fractions (PAFs) of their metabolic risk factors in Iran. Methods: This is a study on 8621 participants aged 45-75 years and older, recruited in the repeated measurement phase of the Golestan cohort study (GCS) in northeast of Iran. The Cox proportional hazards model was used to determine the adjusted hazard ratios (HRs). PAFs were calculated to enumerate CVDs mortality avoidable in the population if metabolic risk factors were eliminated. Results: The mortality of CVDs was attributable to metabolic factors, including high waist circumference (PAF, 28 %, [95 % CI: 16%-38 %]), high fasting blood sugar (FBS) (20 %, [15%-24 %]), overweight and obesity (19 %, [8%-28 %]), high blood pressure (16 %, [11%-21 %]), high low-density lipoprotein cholesterol (LDL-C) (8 %, [1%-15 %]), and high triglyceride (TG) (7 %, [3%-11 %]). Collectively, these metabolic risk factors accounted for 50 % of CVDs deaths. Females (67 %, [50%-78 %]) had a higher joint PAF of metabolic risk factors compared to males (43 %, [27%-55 %]). Conclusions: The pattern of CVDs mortality attributable to metabolic risk factors in this study is not the same as similar studies in other parts of the world and previous studies in Iran. It is imperative that CVDs risk factors be specifically evaluated and addressed in various populations due to variety in geographical and temporal patterns in contribution of metabolic risk factors to CVD mortality.

All-Cause and Cause-Specific Mortality in Middle-Aged Individuals with Positive HBsAg: Findings from a Prospective Cohort Study.

BACKGROUND: While hepatitis B virus (HBV) is the most prevalent cause of adult liver transplants in Iran, the mortality rates and leading causes of death in HBV patients are not well-understood. This study aimed to investigate all-cause and cause-specific mortality among HBsAg positive individuals in a large Iranian cohort. METHODS: The Golestan Cohort Study includes 50045 individuals aged 40-75 residing in Iran's Golestan province, enrolled during 2004-2008. HBsAg test was performed at baseline. For the present study, individuals with hepatitis C coinfection were excluded. All-cause mortality was considered as the primary outcome. The association between HBsAg and different mortality causes was evaluated using Cox proportional hazard models. P value<0.05 was considered significant. RESULTS: The current study included 49667 participants. After 11.33 (median) follow-up years, there were 7,686 total deaths, with 635 deaths in the HBsAg positive group. In the multivariate Cox proportional hazard model, HBsAg positive individuals had higher all-cause (adjusted hazard ratio [aHR]=1.15, 95% CI: 1.06-1.24) and liver-related mortality risk (aHR=7.13; 5.19-9.79). Mortality from colorectal and pancreatic cancers was higher among male HBsAg positive participants (aHRs=2.41 and 2.22, respectively). Nevertheless, cardiovascular diseases (CVDs) and extrahepatic malignancies were the leading causes of death among both HBsAg positive and negative individuals, and liver-related deaths contributed to an overall 10% of deaths in HBsAg positive patients. CONCLUSION: HBV is associated with significant mortality risk from different causes in Iranian adults. However, solely focusing on liver outcomes in Iranian HBV patients might result in overlooking non-liver events, especially CVD and extrahepatic cancers.

Intra-familial Transmission of Chronic Hepatitis B Infection: A Large Population-Based Cohort Study in Northern Iran.

AIM: The aim of this study was to investigate the intra-familial transmission of chronic hepatitis B (CHB) in Golestan province, that has the highest prevalence of CHB in Iran. METHODS: The Golestan Cohort Study (GCS) is a population-based prospective study of 50045 individuals, 40 years or older, initially set-up to study upper GI cancers in Northern Iran. In 2008, a baseline measurement of hepatitis B surface antigen (HBsAg) on the stored serum of all GCS participants identified 3505 HBsAg+ individuals. In 2011, we assessed HBV serological markers in 2590 initially HBsAg+ individuals and their first-degree relatives including spouses (1454) and children (3934). RESULTS: The median (IQR) age of spouses and children were 52 (12) and 25 (12) years respectively. Out of 5388 family members, 2393 (44.5%) had no HBV markers, indicating susceptibility to infection. Of these, 378 (15.8%) were fully-vaccinated children with no apparent response to primary immunization. HBsAg was positive in 2.2% (n = 33) of spouses and 8.2% (n = 325) of children (overall rate of 6.6%). HBcAb was positive in 761 (52.3%) and 914 (23%) spouses and children, respectively. The rate of spontaneous loss of HBsAg (HBsAg-, HBsAb+ and HbcAb+) was 41.3% and 13.9% in spouses and children, respectively. A higher rate of HBsAg+ children (10.2%) was found in families in which the mother was positive for HBsAg compared with families where the father was positive for HBsAg (6.3%) (P < 0.001). When both parents were positive for HBsAg, the rate of HBsAg positivity was high (23.5%, P < 0.001). Despite high virus exposure rates between spouses (52.6 %), the prevalence of HBsAg positivity among them was very low (2.3 %). CONCLUSION: Sexual and parent-to-child transmission are important routes of CHB spread in this population from northern Iran despite the fact that 24 years have passed since the beginning of hepatitis B vaccination in infants. Low percentage of HBsAg positivity in spouses is related to high HBsAg clearance rate among them.

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

BACKGROUND: 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. OBJECTIVES: 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. SEARCH METHODS: 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. SELECTION CRITERIA: All randomised clinical trials using statins as the primary treatment for NAFLD or NASH versus no treatment, placebo, or other hypolipidaemic agents. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.

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.