Characterization of biliary microbiota dysbiosis in extrahepatic cholangiocarcinoma.

Extrahepatic cholangiocarcinoma (CCA) accounts for 3% of digestive cancers. The role of biliary microbiota as an environment-related modulator has been scarcely investigated in CCA, and the putative impact of associated diseases has not been yet assessed. We characterized the biliary microbiota in CCA patients in order to identify a specific CCA-related dysbiosis. The biliary effluents were collected through an endoscopic retrograde pancreatic cholangiography (ERCP) examination involving 28 CCA and 47 patients with gallstones, herein considered as controls. The biliary effluents were submitted to bacterial DNA extraction and 16S rRNA sequencing, using Illumina technology. Overall, 32% of CCA and 22% of controls displayed another associated disease, such as diabetes, pancreatitis, inflammatory bowel disease, or primary sclerosing cholangitis. Such associated diseases were considered in the comparisons that were made. Principal coordinate analysis (PCoA) detected a significant disparity of biliary microbiota composition between CCA patients and controls without an associated disease. Amongst the most abundant phyla, Proteobacteria did not significantly differ between CCA patients and controls, whereas Firmicutes levels were lower and Bacteroidetes higher in CCAs' biliary microbiota than in the controls' microbiota. The most abundant genera were Enterococcus, Streptococcus, Bacteroides, Klebsiella, and Pyramidobacter in CCA's biliary microbiota. Additionally, levels of Bacteroides, Geobacillus, Meiothermus, and Anoxybacillus genera were significantly higher in CCA patients' biliary microbiota, without an associated disease, in comparison with controls. A specific CCA-related dysbiosis was identified as compared to controls independently from associated diseases. This suggests that a microorganism community may be involved in CCA pathogenesis.

Fatty liver index (FLI) and prediction of new cases of non-alcoholic fatty liver disease: A population-based study of northern Iran.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease is considered a major public health concern. The prediction of individuals who can acquire this disease would be valuable. The fatty liver index (FLI) is a non-invasive approach that has shown a good capability for discriminating individuals with non-alcoholic fatty liver disease (NAFLD) from those without it. Thus, this study evaluated the ability of the FLI to predict new cases of NAFLD following a 7-year follow up. MATERIALS AND METHODS: This study was based on the results of follow-up on individuals who did not have NAFLD in 2009-2010, but acquired the disease by 2016-2017. A total of 2241 people who did not have NAFLD in 2009-2010 were evaluated 7 years later by ultrasound so as to diagnose new cases of NAFLD. The FLI was calculated based on data from phase 1 (performed in 2009-2010) of the cohort study. ROC analyses were performed to estimate the predictive ability of the FLI in the diagnosis of new cases of NAFLD. Logistic regression analysis was performed, in which the FLI was considered the predictor and new cases of NAFLD was the outcome. RESULTS: The related AUCs for the FLI in men and women were 0.712 (95% CI = 0.675-0.749) and 0.721 (95% CI = 0.683-0.759), respectively. Based on the current findings, the FLI showed a significant association with NAFLD in multiple logistic regression analyses in both men and women (OR (95% CI) = 1.038 (1.029-1.047), p-value <0.001 in men and OR (95% CI) = 1.032 (1.023-1.041), p-value <0.001 in women in multiple logistic analyses). CONCLUSION: In this study, the FLI was shown to have an acceptable capability of predicting the occurrence of new cases of NAFLD.

Metabolic syndrome and cardiovascular risk assessment tools' estimations of 10-year cardiovascular risk: a population-based study.

Background: This cross-sectional study determines the association between 10-year cardiovascular disease (CVD) risk, estimated using four CVD risk assessment tools, and metabolic syndrome (MetS) in northern Iranian general population. Methods: We used the data of 2371 participants aged 40-74 without any history of diabetes mellitus from a cohort study conducted among 6140 subjects aged 10-90 years in northern Iran. Three definitions of MetS were used. The four CVD risk assessment tools used to estimate the 10-year CVD risk included pooled cohort equations of ACC/AHA, Systematic Coronary Risk Evaluation (SCORE) equations (for low-risk and high-risk European countries), and Framingham general cardiovascular risk profile for use in primary care. Logistic regression was used to determine the association between various definitions of MetS and 10-year CVD risk of ≥5%, ≥ 7.5%, and ≥10%, based on the related risk assessment tools. Results: In men, univariate logistic regression analysis showed the strongest association between 10-year risk of ≥0.1 estimated by Framingham risk profile and the three definitions of MetS. In women, the 10-year risks by Framingham risk profile and SCORE equations for high-risk European countries had stronger associations with various definitions of MetS than others. No significant associations were detected between estimated risks of four risk assessment tools and various definitions of MetS in multivariate logistic regression analyses. Conclusion: No independent associations were observed between estimations of 10-year CVD risk using four risk assessment tools and various definitions of MetS.

The Prevalence of Non-alcoholic Fatty Liver Disease and Diabetes Mellitus in an Iranian Population.

BACKGROUND Type II diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are important causes of morbidity and mortality worldwide. We aimed to estimate the prevalence of DM in the context of NAFLD. METHODS In this cross-sectional study, we studied 5052 participants, aged 18 years and older, of a baseline population-based cohort in northern Iran (N=6143). The prevalence of DM was estimated in individuals with and without NAFLD. The association between NAFLD and T2DM was evaluated using logistic regression with the adjustment of confounding effects of age, sex, body mass index, lipid profiles, and fasting insulin. RESULTS In men, the prevalence (95% confidence interval) of T2DM was 5.34% (4.35%-6.34%) and 15.06% (13.12%-17.00%) in individuals without and with NAFLD, respectively (p <0.001). In women without NAFLD, the prevalence was 8.27% (6.83%-9.71%) while in the presence of NAFLD, the prevalence was 27.21% (24.59%-29.83%), (p <0.001). In univariate analysis, the chance of having T2DM was 3.700 (3.130-4.380) times more in patients with NAFLD compared with subjects without NAFLD (p<0.001). This chance was reduced (Odds Ratio=1.976, 95% CI: 1.593-2.451, p <0.001) after removing the effects of other variables. CONCLUSION The prevalence of T2DM is increased in the context of NAFLD. This condition may be considered as an independent predictor of T2DM.

Non-alcoholic fatty liver disease (NAFLD) and 10-year risk of cardiovascular diseases.

BACKGROUND AND AIMS: The association between cardiovascular diseases (CVD) and non-alcoholic fatty liver disease (NAFLD) was confirmed by a large body of evidence. This study was conducted to determine the association between NAFLD and 10-year CVD risk. METHODS: This study utilized the data of 2804 subjects aged 40-74 years from a cohort study of northern Iran. Two CVD risk assessment tools, American College of Cardiology/American Heart Association and Framingham general cardiovascular risk profile for use in primary care, were utilized to determine the 10-year CVD risk in patients with NAFLD and the individuals without this condition. The mean risks were compared between these two groups. RESULTS: Using ACC/AHA approach, the mean risk in male participants suffering NAFLD was 14.2%, while in men without NAFLD was 11.7% (P-value < 0.0001). Using Framingham approach, the mean risks were 16.0 and 12.7% in men with and without NAFLD, respectively (P-value < 0.0001). Using ACC/AHA approach, the mean risks in female participants with and without NAFLD were 6.7 and 4.6%, respectively (P-value < 0.0001). Applying Framingham approach, the mean risk was 8.2% in women with NAFLD and 5.4% in women without NAFLD (P-value < 0.0001). CONCLUSION: The individuals with NAFLD had a higher risk of 10-year CVD events than individuals without NAFLD, according to both ACC/AHA tool and primary care version of Framingham tool. A large proportion of NAFLD patients fulfill the criteria of statin therapy recommendation, suggesting that statin therapy could reduce 10-year CVD risk in NAFLD patients.

Comparison of cardiovascular risk assessment tools and their guidelines in evaluation of 10-year CVD risk and preventive recommendations: A population based study.

BACKGROUND: Identification of individuals at risk of cardiovascular diseases (CVDs) results in better clinical outcomes and may help policy makers in conscious decision making for community based and national intervention strategies. The main aim of this study was to compare various CVD risk assessment tools and their related guidelines in estimation of 10-year CVD risk and subsequent therapeutic recommendations, respectively. METHODS: Data of 3086 subjects aged 40-74years from a cohort study of northern Iran were utilized in this cross-sectional study. The risks were calculated based on American College of Cardiology/American Heart Association (ACC/AHA) tool, two versions of Systematic Coronary Risk Evaluation (SCORE) equations (for low and high risk European countries) and Framingham approach. We also detected participants who ought to be recommended for treatment based on the specific guidelines related to each of the risk assessment tools. RESULTS: Mean cardiovascular risks were 12.96%, 8.84%, 1.90% and 3.45% in men and 5.87%, 2.13%, 0.8% and 1.13% in women based on ACC/AHA, Framingham, SCORE equation for low-risk European countries and high-risk European countries, respectively. Based on ACC/AHA, Adult Treatment Panel III (ATPIII) and European Society of Cardiology (ESC) guidelines related to SCORE equations for low and high risk European countries 58.2%, 27.1%, 21.1% and 28.6% of men and 39.7%, 33.0%, 29.5% and 30.7% of women were recommended to statin therapy, respectively. CONCLUSIONS: In conclusion, more individuals were recommended for treatment by ACC/AHA guideline than the other guidelines.

Body Roundness Index and Waist-to-Height Ratio are Strongly Associated With Non-Alcoholic Fatty Liver Disease: A Population-Based Study.

BACKGROUND: A strong association between obesity and non-alcoholic fatty liver disease (NAFLD) has been reported. OBJECTIVES: This study was conducted to evaluate if new obesity indices, including a body shape index (ABSI) and body roundness index (BRI), have stronger associations with NAFLD than waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR). METHODS: In this cross-sectional study, we utilized the data of 4,872 participants aged 18 - 74 years from a cohort study conducted among 6,143 subjects in northern Iran. Logistic regression analysis was performed on NAFLD as the outcome and obesity measures (based on Z-score values) as potential predictors. Receiver operating characteristic (ROC) analyses were conducted, in which NAFLD was considered as a reference variable and obesity measures as classification variables. The discriminatory ability of the obesity measures was reported based on area-under-the-curves, and the related cut-off points of BRI and WHtR were determined using the Youden index (YI). RESULTS: Based on our results, BRI (OR = 5.484 for men and OR = 3.482 for women) and WHtR (OR = 5.309 for men and OR = 3.854 for women) showed a higher association with NAFLD than ABSI (OR = 1.363 for men and OR = 1.003 for women) and WHR (OR = 3.123 for men and OR = 1.628 for women). The optimal cut-off points for BRI were 4.00 (sensitivity = 82.7%, specificity = 70.8%) for men and 5.00 (sensitivity = 83.3%, specificity = 71.7%) for women. The optimal cut-off points for WHtR were 0.533 (sensitivity = 82.7%, specificity = 70.8%) for men and 0.580 (sensitivity = 83.3%, specificity = 71.7%) for women. CONCLUSIONS: While BRI and WHtR have equally strong associations with NAFLD, ABSI and WHR have weaker associations with NAFLD than BRI and WHtR.

The Best Obesity Indices to Discriminate Type 2 Diabetes Mellitus.

BACKGROUND: It is expected that the number of people with diabetes will reach 435 million by 2030. Obesity is considered the most important predictor of type 2 diabetes mellitus (T2DM). We conducted the present study to determine the best usual discriminator indices of obesity to diagnose diabetes mellitus (DM). METHODS: Of 6143 subjects aged 10-90 years from a baseline cohort study, the data of 5772 participants aged >18 years and without history of type 1 diabetes were utilized to analyze in this study. The cohort study was carried out in northern Iran and sampling frame was provided from related local health centers. The capability of obesity indices, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and body adiposity index (BAI), in the discrimination of DM was evaluated. Discriminatory capabilities were evaluated using the receiver operating characteristic (ROC) curve. Logistic regression analysis was performed to determine the strength of association between obesity indices and DM. RESULTS: The areas under ROC curve of BAI, BMI, WC, and WHR were 0.6244 (0.5918-0.6570), 0.6214 (0.5908-0.6520), 0.6636 (0.6341-0.6930), and 0.7303 (0.7032-0.7575) in men and 0.5961 (0.5674-0.6249), 0.5963 (0.5690-0.6235), 0.6850 (0.6593-0.7108), and 0.7529 (0.7297-0.7761) in women, respectively. In the multivariate model, one unit increase in Z-score of BMI, WC, and WHR increased the chance of DM by 49%, 65%, and 51% in men and by 17%, 51%, and 67% in women, respectively. No association was found between DM and BAI in this model. CONCLUSIONS: While WHR had an appropriate discriminatory capability for T2DM in the population of northern Iran, BAI and BMI did not.

Prevalence and risk factors of cholelithiasis in Amol city, northern Iran: a population based study.

BACKGROUND: Cholelithiasis is one of the most prevalent gastrointestinal disorders requiring hospitalization.  While different factors influence gallstone formation in patients, these factors are not the same in different societies or in different geographical locations. AIM: To evaluate the epidemiology and risk factors associated with gallstone formation in a large population group, the present survey was conducted in northern Iran. METHODS: In 6143 asymptomatic subjects, the incidence of gallstone formation as well as risk factors were evaluated through a structured questionnaire, physical examination and ultrasonography study. Sample selection was based on stratified cluster systemic randomization. RESULTS: Of these enrolled subjects 3507 (57.1%) were male and 2636 (42.9%) were female with a mean age of 42.71 ± 17.1 years.  The prevalence of gallstones was 0.80%.  On multivariate analysis, the risk of gallstone disease is correlated to rural locale, diastolic hypertension, age, and TG levels.  However, systolic hypertension, glucose serum levels and obesity were also significantly associated with the presence of gallstones. CONCLUSION: The present study proposes that the rate of gallstone disease in northern Iran is lower than previous studies have reported, and that most of the risk factors can be prevented by changes in lifestyle and diet.