Mediators of dietary diversity score (DDS) on NAFLD in Iranian adults: a structural equation modeling study.

BACKGROUND: The current study examines the association between the Dietary Diversity Score (DDS) and nonalcoholic fatty liver disease (NAFLD) in Iranian adults using structural equation modeling (SEM). METHODS: A sample of 3220 adults from the Amol Cohort Study was recruited for this cross-sectional study. Dietary acid load (DAL) and DDS were calculated using the data obtained from a validated food frequency questionnaire. Anthropometric parameters, blood pressure, biochemical measurements, and liver ultrasonography were evaluated according to standard protocols. RESULTS: DDS was neither directly nor indirectly associated with a greater prevalence of NAFLD. In the second model (DDS sub-scores model), the association of DAL with NAFLD was fully mediated through waist circumference (WC) (of DAL to WC: ß = 0.14, P < 0.0001, and of WC to NAFLD: ß = 0.50, P < 0.001). Vegetable and fruit diversity scores had a significant negative indirect relationship with NAFLD prevalence through DAL (ß = -0.06, P = 0.001, ß = -0.10, P < 0.001, respectively). Meat diversity score was positively associated with NAFLD prevalence in a full mediational process through DAL (ß = 0.12, P < 0.001). The SEM fit indices suggested a reasonably adequate fit of the data to the DDS model (Χ2/df = 4.76, GFI = 0.98, AGFI = 0.97, IFI = 0.97, CFI = 0.97, RMSEA = 0.03, and SRMR = 0.02) and its sub-scores model (Χ2/df = 4.72, GFI = 0.98, AGFI = 0.97, IFI = 0.95, CFI = 0.95, RMSEA = 0.03, and SRMR = 0.02). CONCLUSION: Meat diversity and lack of vegetable and fruit diversity were indirectly associated with NAFLD prevalence through DAL and WC mediators. Interventions for NAFLD may be more successful if they target a lower intake of animal protein sources and dietary diversity, particularly vegetable and fruit diversity.

Long-Term Follow-Up of Thalassemia Major Patients with Hepatitis C Virus Treated with Sofosbuvir and Daclatasvir: A Cohort Study.

BACKGROUND: Treatment of Chronic Hepatitis C virus (HCV) infection in patients suffering from hereditary ß-thalassemia major is a concern due to drug complications and liver malfunction. The aim of the present study was to evaluate treatment outcome of Direct-Acting Antiviral (DAA) therapy in thalassemia major patients infected with HCV in a three year follow-up. METHODS: In a cohort study, long-term safety and efficacy of DAA therapy were evaluated in a group of thalassemia major patients suffering from chronic HCV infection. Hematologic and biochemical parameters as well as liver Fibroscan monitoring were assessed at the onset and three years after the treatment. RESULTS: From among 84 patients enrolled in the study, 53.6% were males, 36.9% had cirrhosis, 96.4% had a history of Desferal usage, and 78.6% had a history of splenectomy. Unfortunately, 7 participants (8.3%) died prior to the end of follow-up with nearly half of them having Iron overload and heart failure complications. Fibroscan score, ALT, AST, and ferritin were significantly lower compared with baseline evaluation, while Hb, creatinine, and direct bilirubin increased significantly in the third year after the treatment. CONCLUSION: Safety and efficacy of Sofosbuvir and Daclatasvir in thalassemia patients assessed previously but our three year follow-up showed their mild complications and death into a long-term period after DAAs treatment and 91.7% three year survival rate, which may affected by other confounding factors, such as liver malfunction and Iron overload.

Predictive ability of six obesity measures to identify 7-year fatal and non-fatal cardiovascular events: A population-based cohort study.

Background: Globally, most people die from cardiovascular diseases. We aimed to compare predictive ability of six obesity indices, including body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio, conicity index, and abdominal volume index, to identify people at risk of fatal and non-fatal cardiovascular events, in a cohort study. Methods: We studied 5147 participants in a baseline population-based cohort study conducted in northern Iran. The obesity measures were calculated in enrollment phase (2009-2010), and the cardiovascular events were recorded during a 7-year follow-up phase (2010-2017). Receiver operating characteristic (ROC) analyses and Cox hazard regression models were applied, considering the obesity measures as predictors, and the 7-year cardiovascular events as outcomes. Multiple Cox models were adjusted by age, prior history of cardiovascular diseases, chronic kidney diseases, insulin resistance, diabetes mellitus, dyslipidemia, hypertension, and smoking status. Results: Conicity index showed the highest performance in predicting 7-year fatal and non-fatal cardiovascular events with areas under the ROC curve of 0.77 [95% confidence interval: 0.71-0.82], and 0.63 [0.59-0.68] in men, and 0.80 [0.74-0.87], and 0.65 [0.60-0.71] in women, respectively. In multiple Cox models, the obesity measures had no significant associations with cardiovascular events in women. In men, only waist-to-height ratio was independently associated with 7-year non-fatal cardiovascular events (hazard ratio: 1.19 [95% confidence interval: 1.01-1.38]). Conclusions: Although waist-to-height ratio had an independent association with 7-year non-fatal cardiovascular events in men, conicity index showed the best ability to predict 7-year fatal and non-fatal cardiovascular events in our study.

A randomized triple-blind controlled clinical trial evaluation of sitagliptin in the treatment of patients with non-alcoholic fatty liver diseases without diabetes.

The current study aimed to evaluate the efficacy of sitagliptin vs. placebo in treating non-alcoholic fatty liver disease (NAFLD). In a triple-blind randomized clinical trial, we assigned 120 eligible subjects with NAFLD to receive daily dosing of 50 mg sitagliptin (n = 60) or the placebo (n = 60) for 56 weeks and lifestyle modification in both groups. Laboratory and anthropometric outcomes were measured, and liver stiffness was assessed using a fibroscan. The primary outcome measures were changes from baseline in fibrosis scores and liver transferases. Out of 120 patients randomized into sitagliptin and placebo groups, 76 patients completed the trial, of whom 44 were in the sitagliptin and 32 in the placebo groups. Patients receiving sitagliptin showed a significant decrease in the fibrosis scores (P = 0.001). The reductions in the alanine aminotransferase (AST) (P = 0.036) and aspartate AST (P < 0.001) levels were also statistically significant. The effect of sitagliptin in reducing fibrosis scores was significantly greater in normal-weight and overweight individuals than in obese individuals (p = 0.036, and p = 0.018, respectively), whereas the effects of sitagliptin on AST levels were greater among overweight/obese patients (p = 0.028, and p = 0.016, respectively). Sitagliptin reduced fibrosis scores and liver enzymes in NAFLD patients after 56 weeks of therapy. The changes in fibrosis scores were more prominent in patients with normal weight and overweight than obese patients, whereas the effects on AST levels were greater among overweight/obese patients. Other randomized trials with larger sample sizes and longer treatment durations may be required before precise results can be reached. Clinical Trial Registration: [https://www.irct.ir/trial/46140], identifier [IRCT20140430017505N2].

Empirically-Derived Dietary Patterns in Relation to Non-Alcoholic Fatty Liver Diseases Among Adult Participants in Amol, Northern Iran: A Structural Equation Modeling Approach.

Dietary modifications remain the mainstay in managing nonalcoholic fatty liver disease (NAFLD). Published data on the effect of overall dietary patterns on NAFLD is scarce. The present study aims to extract the dietary patterns and investigate their association to NAFLD by gender, using structural equation modeling, among adult participants in Amol, northern Iran. In this cross-sectional study, data from 3,149 participants in the Amol cohort study (55.3% men, n = 1,741) were analyzed. Usual dietary intake was assessed by a validated 168-items semiquantitative food frequency questionnaire. We classified major dietary patterns by explanatory factor analysis (EFA) and confirmatory factor analysis (CFA). NAFLD diagnosis was based on ultrasound scanning, including increased hepatic echogenicity, abnormal appearance of hepatic arteries, and diaphragm in the absence of excessive alcohol consumption. Multivariable logistic regression and structural equation modeling (SEM) were used to explore the relationship between dietary patterns and NAFLD. Three distinct dietary patterns, including western, healthy, and traditional/mixed dietary patterns, were identified. Adult male who adhere to the western dietary pattern were more affected with NAFLD risk [Q1, Q2, Q3, Q4, odds ratio (OR) = 1, 1.16, 1.34, 1.39; 95% confidence interval (CI) = 0.83-1.61, 0.96-1.85, 0.98-1.96, p trend = 0.04, respectively]. A full mediating effect of healthy dietary pattern, western dietary pattern, and traditional dietary pattern via dietary acid load (DAL) proxy (of dietary patterns to DAL: ßstd = -0.35, p < 0.006, ßstd = 0.15, p = 0.009, and ßstd = 0.08, p = 0.001, respectively), on NAFLD was found through mediation analysis using SEM. A western dietary pattern comprising frequent intake of salty and sweet snacks, soft drinks, refined grains, processed meats, cooked and fried potatoes, eggs, and coffee was associated with a higher odds of NAFLD in an Iranian male population. Additionally, our findings might provide a mechanistic explanation for the association between dietary patterns and NAFLD via DAL proxy. However, further prospective studies, including assessing acid-base biomarkers, are needed.

Simultaneous Hepatitis C Virus Genotyping and Variant Detection in Patients with Thalassemia: A Single-Center Phylogenetic Study.

BACKGROUND: Hepatitis C virus (HCV) genotype distribution is different in various regions. A variety of strategies could be used to detect HCV genotypes and subtypes. The aim of the present study was to introduce a genotyping method by an in-house protocol that could be used to determine HCV drug-resistant variants and phylogeny studies. METHODS: Samples from 91 patients with thalassemia were used for HCV genotyping by Cobas 4800 platform, and 50 cases of 1a, 1b, and 3a genotypes underwent amplification and sequencing of NS5A and NS5B by using consensus primers via conventional reverse transcription-polymerase chain reaction (RT-PCR) method. An ABI 3730xl system used for direct sequencing. Raw sequences were analyzed by popular bioinformatics software MEGA6 and CLC workbench 5. Phylogenetic construction was drawn using 1000 replicates bootstrap by the neighbor-joining method. Multiple sequence alignment (MSA) was performed for mutation detection. RESULTS: Sequencing results of 50 HCV isolates subtypes 1a (31/45), 3a (15/22) and 1b (4/8) NS5A and NS5B genes showed there were 72 NS5A and 105 NS5B mutations. Moreover, 8 resistant associated substitutions (RASs) were identified in nine thalassemia cases by multiple sequence alignment (MSA) protein analysis. The phylogenetic tree construct drew confirmed by the Cobas HCV genotyping results. CONCLUSION: The phylogenetic analysis could be a useful tool for HCV genotyping in case of determining the drug-resistant substitutions; however, it is time-consuming and needs expert analysis and interpretation. This preliminary study in Iranian patients with thalassemia introduces specific conventional RT-PCR to find RASs to direct acting antivirals (DAAs) and subtype determination at the same time.

Effect of Baseline Resistance-Associated Substitutions on Thalassemia Patients with Chronic HCV Infection: A Two-Year Follow-Up.

BACKGROUND Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection showed the presence of resistant-associated substitutions (RASs). The aim of the present study was to carry out a follow-up of patients with baseline RASs to report the impact of RASs on DAA therapy outcome. METHODS In a cohort study, we analyzed NS5A and NS5B RASs among nine thalassemia cases by baseline RASs. In a 2-year follow-up, we analyzed viral markers and biochemical and hematological parameters of the participants and their sustained virologic response (SVR). Statistical analyses were performed using SPSS software version 22. RESULTS RASs for HCV subtype 1a included M28V, L31M, and H58P. For subtype 1b: L28M, R30Q, S24F, and C316N. And for subtype 3a: C316S, and S24F. In patients with cirrhosis (n = 5), ALT (p = 0.001) and AST (p = 0.007) levels were significantly reduced after treatment, and creatinine level slightly increased (p = 0.025). However, no significant data was observed in non-cirrhotic patients following the treatment. CONCLUSION The present study did not show any adverse effects of DAA therapy among patients with thalassemia suffering from chronic HCV infection with baseline RASs. Furthermore, reduction in ferritin and liver stiffness levels after DAA therapy could show the efficacy of DAA in such patients.

The Ability of the Framingham Steatosis Index (FSI) to Predict Non-alcoholic Fatty Liver Disease (NAFLD): A Cohort Study.

BACKGROUND: The utilization of indexes for the diagnosis of non-alcoholic fatty liver disease (NAFLD) can be valuable. This study was conducted to determine the ability of the Framingham steatosis index (FSI) to distinguish between people with NAFLD and those without and to predict people at risk of NAFLD to establish the need for lifestyle modifications in such individuals. METHODS: Our study was conducted in two phases from 2009-2010 (phase I) to 2016-2017 (phase II). A total of 4670 people in northern Iran were included. NAFLD was diagnosed by ultrasound. The FSI was calculated based on age, sex, hypertension, diabetes mellitus status, liver enzyme levels and triglyceride levels. Receiver operating characteristic (ROC) analysis was conducted to determine the discriminatory and predictive abilities of the FSI. To remove the confounding effects of potential mediators, logistic regression was performed in which NAFLD was considered the outcome and the FSI as the predictor. RESULTS: The odds ratios of the FSI when the outcome was the prevalence of NAFLD in phase I and when the outcome was new cases of NAFLD from 2009-2010 to 2016-2017 were 4.909 (4.243-5.681) and 2.453 (2.024-2.972), respectively (P<0.001). The areas under the curve (AUCs) for the discriminatory and predictive abilities of the FSI were 0.8421 (95% CI: 0.8314-0.8527) and 0.7093 (95% CI: 0.6863-0.7322), respectively. CONCLUSION: The FSI has a strong ability to diagnose NAFLD while it has an acceptable ability to predict the occurrence of new cases of NAFLD.

Tissue Sampling through Endoscopic Ultrasound-Guided Fine Needle Aspiration versus Endoscopic Retrograde Cholangiopancreatographic Brushing Cytology Technique in Suspicious Malignant Biliary Stricture.

BACKGROUND Differentiation of benign and malignant biliary strictures plays a pivotal role in managing biliary strictures. Brush cytology via endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are two diagnostic methods. In the present study, we aimed to compare the accuracy of the results of EUS-FNA and ERCP-based sampling of biliary strictures. METHODS In a prospective study, between January 2019 and March 2020, patients with indeterminate biliary strictures who had no history of hepatobiliary surgery, opium usage, cancer of pancratobiliary system, and acute liver disease were selected. They underwent EUS and ERCP in the same session. They were followed up for 6 months, and the sensitivity, specificity, positive and negative predictive values, and accuracy of these imaging modalities were compared. RESULTS A total of 60 patients were enrolled. 28 lesions were located in the distal and 32 lesions in the proximal parts of the biliary tree. 55 malignant and 5 benign lesions were diagnosed. The sensitivity and accuracy of EUS-FNA and ERCP tissue sampling were 78.2% and 80.0% versus 50.9% and 55.0%, respectively (p = 0.024). The combination of both methods improved the sensitivity and accuracy to 85.5% and 86.7%, respectively. Regarding the location, EUS-FNA is superior to ERCP-brush cytology in diagnosing proximal lesions with sensitivity and specificity of 73.3% and 75.0% vs. 50.0% and 53.1%, respectively (p = 0.04). CONCLUSION EUS-FNA is superior to ERCP brushing in the diagnosis of indeterminate biliary strictures, particularly in distal lesions. Combining ERCP brushing and EUS-FNA improves the diagnosis accuracy.

Non-alcoholic fatty liver disease is not independent risk factor for cardiovascular disease event: A cohort study.

BACKGROUND: There are no consistent results between previous studies for an independent association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) events. AIM: To determine if there is an independent association between NAFLD and CVD events. METHODS: In the present study, valid outcome data of 4808 subjects were available for phase 2 of our cohort study. These subjects had been followed up for seven years from phase 1, beginning in 2009-2010 to phase 2 during 2016-2017. Simple and multiple Cox proportional models were used to determine the association between NAFLD in the primary phase of the cohort and subsequent fatal and non-fatal CVD events during follow-up. RESULTS: The incidence of non-fatal CVD events in males with NAFLD was significantly higher (P = 0.004) than in males without NAFLD. A positive association was demonstrated between NAFLD and non-fatal CVD events in males (Hazard ratio = 1.606; 95%CI: 1.166-2.212; P = 0.004) by the simple Cox proportional hazard model, but no independent association was detected between these in the multiple Cox models. CONCLUSION: No independent association was detected between NAFLD and CVD. It is likely that diabetes mellitus and age may be the principle mediators in this regard.

10-year risk of cardiovascular disease and body mass index in association with the obesity paradox.

BACKGROUND: Some recent studies reported an inverse association between obesity and risk of cardiovascular diseases (CVD), heart failure related mortality rate, outcomes of myocardial infarction (MI), and the consequences of cardiovascular events interventions; this inverse association was named the obesity paradox. The present study was conducted with the aim to determine whether the obesity paradox will be detectable when the 10-year risk of CVD is estimated using CVD risk assessment tools. METHODS: The related data of 2910 subjects aged 40-74 years obtained in our cohort study that was carried out among 6140 subjects in Amol, in northern Iran, was included in this study. CVD risk assessment tools were used to estimate the 10-year risk of CVD. Obesity was evaluated using 4 indices, including waist circumference (WC), waist to height ratio (WHtR), waist to hip ratio (WHR), and body mass index (BMI). The receiver operating characteristic (ROC) curve analysis was utilized to evaluate the discriminatory power of obesity indices for 10-year risk of CVD. RESULTS: Categorizing the participants to with and without obesity according to BMI showed that a significantly higher proportion of men with obesity had a 10-year risk of CVD ≥ 7.5% and ≥ 10% according to American College of Cardiology/American Heart Association (ACC/AHA) and the Framingham approaches, respectively. A higher proportion of women without obesity had a 10-year risk of CVD ≥ 7.5% than women with obesity based on the ACC/AHA equation (28.54% vs. 24.15%; P = 0.0707). BMI had a non-significant AUC (< 0.5) according to the the ACC/AHA equation. CONCLUSION: BMI showed a weak and non-significant inverse association with 10-year risk of CVD estimated using pooled cohort equations of ACC/AHA in women. However, this result cannot directly provide enough evidence for the obesity paradox.

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.

The Comparison of the Plasma Levels of the Lead Element in Patients with Gastrointestinal Cancers and Healthy Individuals.

Back ground and Aim: Heavy metals are considered as risk factors in the development of some types of cancers. In this context, the lead (Pb) along with its biological impacts on the human body has raised significant concerns in public health. The aim of this study was to compare the plasma levels of the lead element in patients with gastrointestinal (GI) cancer and healthy subjects to examine whether this element has a role in the susceptibility of cancer. Methods: In a case-control study conducted between March 2016 to February 2017, the plasma levels of the lead were assessed. One-hundred patients with upper and lower GI cancers, as well as one-hundered healthy subjects who were age- and sex-matched participated in our study. A classic flame atomic absorption spectroscopy (FAAS) method was employed for the determination of the lead element in plasma levels of all subjects. Results: The mean age of patients was 53.8±10.6 years old. The patient group consisted of 51 male and 49 female patients. The results showed that the concentrations of Pb were lower than the defined toxic levels. The comparison of the mean levels of Pb between the case and control groups revealed that there was no statistically significant difference even when the gender, age, and history of smoking were included in the statistical analysis. Our findings showed that the concentration of Pb is significantly associated with the type of cancer (p<0.003) and the location of the tumor (whether upper or lower tract was affected) (p<0.003). Conclusion: Lead may contributes to the pathology and progression of GI cancers but we can not conclude that it involved in the causation or susceptibility of healthy individuals to develop GI cancer.

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.