A population-based prospective study on obesity-related non-communicable diseases in northern Iran: rationale, study design, and baseline analysis.

Background: Iran is facing an epidemiological transition with the increasing burden of non-communicable diseases, such as obesity-related disorders and cardiovascular diseases (CVDs). We conducted a population-based prospective study to assess the prevalence and incidence rates of CVDs and obesity-related metabolic disorders and to evaluate the predictive ability of various CVD risk assessment tools in an Iranian population. Method: We enrolled 5,799 participants in Amol, a city in northern Iran, in 2009-2010 and carried out the first repeated measurement (RM) after seven years (2016-2017). For all participants, demographic, anthropometric, laboratory, hepatobiliary imaging, and electrocardiography data have been collected in the enrollment and the RM. After enrollment, all participants have been and will be followed up annually for 20 years, both actively and passively. Results: We adopted a multidisciplinary approach to overcome barriers to participation and achieved a 7-year follow-up success rate of 93.0% with an active follow-up of 5,394 participants aged 18-90 years. In the RM, about 64.0% of men and 81.2% of women were obese or overweight. In 2017, about 16.2% and 5.2% of men had moderate or severe non-alcoholic fatty liver disease, while women had a significantly higher prevalence of metabolic syndrome (35.9%), and type 2 diabetes mellitus (20.9%) than men. Of 160 deceased participants, 69 cases (43.1%) died due to CVDs over seven years. Conclusion: The most prevalent obesity-related chronic disease in the study was metabolic syndrome. Across the enrollment and RM phases, women exhibited a higher prevalence of obesity-related metabolic disorders. Focusing on obesity-related metabolic disorders in a population not represented previously and a multidisciplinary approach for enrolling and following up were the strengths of this study. The study outcomes offer an evidence base for future research and inform policies regarding non-communicable diseases in northern Iran.

The association between dietary inflammatory index (DII) scores and c-reactive protein (CRP) and nonalcoholic fatty liver disease (NAFLD) in a general population cohort.

BACKGROUND AND AIMS: Although there is extensive literature showing the ability of the dietary inflammation index (DII®) to predict concentrations of plasma inflammatory markers, few studies are testing the association between DII scores and nonalcoholic fatty liver disease (NAFLD). Considering the high prevalence of NAFLD and its complications, we conducted a validation study of DII scores and examined its association with NAFLD in the general adult population of Iran. METHODS: This cross-sectional study was conducted on 3110 adult participants in the Amol Cohort Study (AmolCS) who underwent abdominal ultrasonography to diagnose NAFLD. DII and energy-adjusted DII (E-DII™) scores were computed using data from a valid semi-quantitative 168-item food frequency questionnaire (FFQ). Multivariable logistic regression adjusting for socio-demographic, lifestyle, and health-related factors was used to assess association. RESULTS: The EDII was associated with CRP inflammatory biomarker. Participants in the highest, i.e., most pro-inflammatory tertile had the highest odds of NAFLD by ultrasound in all models [fully adjusted model: OR (95 % CI) tertile3vs.1:1.54 (1.05-2.05); Ptrend = 0.04, and 1.63 (1.19-2.21); Ptrend = 0.03 in women and men, respectively]. The highest tertile had the highest OR for NAFLD by fatty liver index (FLI) only in men [fully adjusted model OR (95 % CI) tertile3vs.1: 1.77 (1.15-2.71); Ptrend = 0.01]. Similar results were also obtained for NAFLD by hepatic steatosis index (HSI) in women [fully adjusted model: OR (95 % CI) tertile3vs.1: 1.70 (1.12-2.58); Ptrend = 0.03]. The results of the fully adjusted multivariable model of liver markers and NAFLD status, stratified by gender and abdominal obesity, revealed that the highest tertiles had the highest OR for NAFLD by ultrasound and NAFLD by FLI only in men without abdominal obesity [fully adjusted model: OR (95 % CI) tertile3vs.1: 1.83 (1.17-2.84); Ptrend = 0.03, and, respectively]. NAFLD by FLI tended to increase strongly with tertile E-DII scores in men without abdominal obesity in crude and three adjusted models [full-adjusted model: OR (95 % CI) tertile3vs.1: 3.64 (1.56-8.46); Ptrend = 0.005]. By contrast, women with abdominal obesity in the highest tertile had the highest OR for NAFLD by ultrasound in all models [full-adjusted model: OR (95 % CI) tertile3vs.1: 1.67 (1.07-2.62); Ptrend = 0.02]. CONCLUSIONS: Our results suggest that diet plays a role in regulating inflammation. Additionally, we observed an inflammatory diet predicts the risk of NAFLD in Iranian adults. However, longitudinal studies are required in order to further substantiate the utility of the DII in the development of more effective dietary interventions among populations at risk of chronic disease.

Genetic variations in IKZF3, LET7-a2, and CDKN2B-AS1: Exploring associations with metabolic syndrome susceptibility and clinical manifestations.

BACKGROUND AND AIM: Metabolic syndrome (MetS) increases the risk of atherosclerosis and diabetes, but there are no approved predictive markers. This study assessed the role of specific genetic variations in MetS susceptibility and their impact on clinical manifestations. METHOD: In this study, a genotype-phenotype assessment was performed for IKZF3 (rs907091), microRNA-let-7a-2 (rs1143770), and lncRNA-CDKN2B-AS1 (rs1333045). RESULTS: Analyses indicate that while rs907091 and rs1143770 may have potential associations with MetS susceptibility and an increased risk of atherosclerosis and diabetes, there is an observed trend suggesting that the rs1333045 CC genotype may be associated with a decreased risk of MetS. The genotypes and allele frequencies of rs1333045 were significantly different between studied groups (OR = 0.56, 95% CI 0.38-0.81, p = 0.002, and OR = 0.71, 95% CI 0.55-0.92, p = 0.008), with the CC genotype displaying increased levels of HDL. Furthermore, the rs907091 TT genotype was associated with increased triglyceride, cholesterol, and HOMA index in MetS patients. Subjects with the CC genotype for rs1143770 had higher HbA1c and BMI. In silico analyses illustrated that rs907091 C remarkably influences the secondary structure and the target site of a broad spectrum of microRNAs, especially hsa-miR-4497. Moreover, rs1333045 creates a binding site for seven different microRNAs. CONCLUSION: Further studies on other populations may help confirm these SNPs as useful predictive markers in assessing the MetS risk.

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].

Dietary Acid Load (DAL), Glycated Hemoglobin A1c (HbA1c), and Metabolic Syndrome (MeS) Mediate the Association of the Adherence to the Dietary Approaches to Stopping Hypertension (DASH) and Mediterranean Diet (MeD) With Nonalcoholic Fatty Liver Disease.

The study aimed to investigate the association of adults adhering to Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diet (MeD) with nonalcoholic fatty liver disease (NAFLD) using structural equation modeling (SEM) in Iran. In this population-based cross-sectional study, 3,220 adults (44.65% female) aged ≥18 years were selected from the Amol Cohort Study (AmolCS). The dietary intakes were assessed by a validated 168-item semi-quantitative food-frequency questionnaire (FFQ). Residual method energy adjustment of MeD and DASH scores were calculated. Demographic characteristics and anthropometric and laboratory measurements were collected. NAFLD was diagnosed by an expert radiologist via ultrasound sonography. Based on the primary hypothesis, DASH, MeD, and NAFLD were fitted into models. Metabolic syndrome (MeS) as a potential risk factor directly affected NAFLD risk in all these models. In both genders, the higher adherence to DASH negatively affected NAFLD risk indirectly through the two following paths. (1) Dietary acid load (DAL) and metabolic syndrome (2) DAL and hemoglobin A1c (HbA1c). In addition, the higher DAL positively affected NAFLD risk among male participants indirectly via increasing HbA1c level and MeS (from DAL to HbA1c: ß = 0.07, P < 0.001; from HbA1c to MeS: ß = 0.10, P < 0.001). Similarly, in both genders, the relationship between MeD and NAFLD was mediated through (1) DAL, HbA1c, and MeS and (2) DAL and MeS. Further, among male participants, the MeD and NAFLD risk were also associated via the mediators of HbA1c and MeS. In female participants, the higher MeD score was directly associated with a reduction of NAFLD risk (ß = -0.07, P = 0.008). The present study found three important mediators, including DAL, HbA1c, and MeS, in the association of DASH and MeD scores with NAFLD risk. Preventive and therapeutic interventions should target the mediators, including DAL, HbA1c, MeS, and its components, to reduce NAFLD incidence in the general population.

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.

Favorable association between Mediterranean diet (MeD) and DASH with NAFLD among Iranian adults of the Amol Cohort Study (AmolCS).

Nonalcoholic fatty liver disease (NAFLD) is an emerging cause of chronic liver diseases and a major health problem worldwide. Dietary patterns may play a critical role in controlling and preventing this disease, but the available evidence is scarce. The current study aims to ascertain the association of adherence to the Dietary Approach to Stop Hypertension (DASH) diet and Mediterranean diet (MeD) with nonalcoholic fatty liver disease (NAFLD) among Iranian adults of the Amol Cohort Study (AmolCS). In a cross-sectional analysis among 3220 adults (55.3% men), age ≥ 18 years (46.96 ± 14.67), we measured usual dietary intake with a validated food frequency questionnaire (FFQ) and then calculated dietary pattern scores for DASH and MeD. Sociodemographic and lifestyle factors were collected by a structured questionnaire. The presence and degree of NAFLD were also determined by abdominal sonography. Multiple regression models were used to estimate NAFLD odds across tertiles of DASH and Mediterranean dietary scores. Dietary DASH and Mediterranean components were adjusted for total energy intake, based on the residual methods. After adjusting for multiple potential confounders, we found an inverse association of DASH and MeD with NAFLD (Ptrend = 0.02, and Ptrend = 0.002, respectively). Those in the highest tertiles of adherence to the DASH and MeD had the lowest risk for NAFLD (OR = 0.80, 95%CI = 0.66-0.96, OR = 0.64, 95%CI = 0.52-0.78, respectively). The results of logistic analysis of MeD, stratified by gender and abdominal obesity, revealed the favorable association was more pronounced in women (OR = 0.42, 95%CI = 0.29-0.61, Ptrend = 0.004), and in participants with or without abdominal obesity (OR = 0.62, 95% CI = 0.47-0.81, Ptrend = 0.03, OR = 0.64, 95%CI = 0.475-0.91, Ptrend = 0.04, respectively). Similar results were obtained for the adherence to DASH diet score with the prevalence of NAFLD patients with abdominal obesity (OR = 0.75, 95% CI = 0.57-0.97, Ptrend = 0.04). The findings suggested the favorable association between DASH and MeD with NAFLD in Iranian adults, especially women and subjects with or without abdominal obesity. Further prospective investigations are needed to confirm the integrity of our findings.

Relationship between dietary macronutrient composition and non-alcoholic fatty liver disease in lean and non-lean populations: a cross-sectional study.

OBJECTIVE: The current study aimed to customize dietary changes for lean patients with non-alcoholic fatty liver disease (NAFLD). DESIGN: The current study was done with a population-based cross-sectional design. The FFQ was used to analyse dietary macronutrient intake and ultrasonography results for NAFLD diagnosis. The study subjects were divided into the lean and non-lean groups based on their BMI (< 25 and ≥ 25). Multivariable logistic regression was used to evaluate the relationship between dietary macronutrients and NAFLD. Substitution analyses were also performed. SETTING: Amol and its suburban areas in Iran. PARTICIPANTS: Adults in the age range of 18 to < 65 with full relevant data. RESULTS: Among the total study subjects (2308), 46·7 % had fatty liver. The substitution of polysaccharides for animal protein and SFA in the lean group resulted in a significant NAFLD reduction, whereas the substitution of SFA for all types of macronutrients, except for n-6 and mono-disaccharides, led to a significant increase in NAFLD (P < 0·05). In non-lean participants, the substitution of MUFA for mono-disaccharides resulted in a significant reduction of NAFLD (P < 0·05). In this group, the substitution of SFA and mono-disaccharides for MUFA, and n-6 for all macronutrients, except vegetable protein and SFA, were significantly related to an increase in NAFLD (P < 0·05). CONCLUSIONS: Lower lean NAFLD is correlated with increasing polysaccharides in exchange for SFA and animal protein intake, whereas lower non-lean NAFLD is correlated with increasing MUFA in exchange for mono-disaccharides and reducing n-6 and SFA.

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.

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.

Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) at baseline of treatment in thalassemia patients: a referral center study.

Patients with thalassemia major are at high risk of hepatitis C through blood transfusion from donors infected by hepatitis C virus (HCV). The use of direct-acting antiviral (DAA) therapy against such HCV infections has increased in different populations. However, resistant viral variants can affect treatment outcomes, and therefore improved surveillance strategies are needed. Accordingly, we aimed to evaluate resistance-associated substitutions (RASs) to HCV DAAs at the baseline of treatment in thalassemia patients in a referral center. Out of 89 thalassemia patients who suffered from HCV infection and were referred to our center between 2016 and 2017, 43 underwent further analysis of the HCV nonstructural proteins NS5A and NS5B using polymerase chain reaction (PCR) sequencing methods. Unique primers were designed using bioinformatics software for separate detection of HCV subtypes 1a, 3a, and 1b. Detection of RASs was performed based on previously published literature. Statistical analysis was carried out using SPSS version 19. The participants, 60.4% (26/43) of whom were male, had a mean age ± standard deviation (SD) of 33.0 ± 5.0 years. HCV subtype 1a was found in 27 cases, 3a in 13, and 1b in three. In HCV subtype 1a there were 163 mutations in NS5A and 212 mutations in NS5B. The frequency of RASs was 20.9% (8 RASs in 9 patients), including M28V and H58P in subtype 1a, L28M, R30Q, C316N, and C316S in subtype 1b, and S24F in subtype 3a. Statistically, the subtype 1b and a higher mutation rate in NS5A were associated with RASs (p-value < 0.05). The emergence of natural RASs to HCV DAAs serves as a warning of the risk of drug resistance in response to the broad usage of antivirals. However, relapses in these DAA-treated HCV-infected thalassemia patients are rarely reported. Our findings indicate that the prevalence of RASs prevalence at baseline was 20.9% in these patients, and this calls for extrapolation to a larger population study, as highlighted in other studies, with larger sample sizes, high-throughput methods, and follow-up in order to fully evaluate treatment outcomes in RASs-detected individuals. Optimized therapeutic strategies, particularly in complex, difficult-to-cure patients, can effectively prevent DAA treatment failure as a result of selection for RASs.

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.

Metabolic Syndrome Is Associated with Health-Related Quality of Life in Suspected Patients with Nonalcoholic Steatohepatitis.

OBJECTIVE: This study was designed to examine the effect of metabolic syndrome (MetS) on health-related quality of life (HRQOL) in patients with suspected nonalcoholic steatohepatitis (NASH). SUBJECTS AND METHODS: Three hundred thirty-two patients (236 males and 96 females) with suspected NASH from the Amol cohort study were included in this study. MetS was diagnosed based on Adult Treatment Panel III criteria and HRQOL was measured using the 12-Item Short-Form Health Survey (SF-12) questionnaire (with 8 subscales and 2 summary components). A multivariable linear regression model was used to assess the independent effect of MetS on HRQOL. RESULTS: The mean age of the study population was 42 ± 13 years (range 18-82). The prevalence of MetS was 43.4% (n = 144) and the mean scores on the Physical Component Summary (PCS) and the Mental Component Summary were 72.4 ± 20.86 and 42.7 ± 12.42, respectively. The multivariable linear regression model showed that MetS was negatively associated with 4 subscales of HRQOL that included: role limitations due to physical problems (RP) (B = -14.05, p = 0.004), bodily pain (BP) (B = -7.37, p = 0.02), vitality (VT) (B = -7.72, p = 0.022), and role limitations due to emotional problems (RE) (B = -12.67, p = 0.005) after adjustment for other variables. Also, MetS had a borderline association with the general health and mental health subscales and the PCS (p < 0.1). CONCLUSION: In this study, there was a strong association between MetS and 4 subscales (RP, BP, VT, and RE) of HRQOL in patients with suspected NASH; this could be considered as a part of health policy to improve general health.

Identifying the pattern of unhealthy dietary habits among an Iranian population: A latent class analysis.

Background: An unhealthy diet is one of the most important risk factors for chronic diseases. The goal of this study was to use the latent class analysis (LCA) modeling to define unhealthy diet habits among an Iranian population. Methods: This cross-sectional study was conducted within the framework of Amol (North of Iran) cohort health study (Phase 1). The participants aged 10 to 90 years. All participants provided written informed consent. Latent class analysis was used to classify the participants of the study. All analyses were conducted by PROC LCA in SAS 9.2 software. Significance level was set at 0.05. Results: The mean age of the participants was 42.58±17.23 years. Four classes of individuals with different diet habits were identified using LCA modeling: class 1: individuals with healthy diet patterns (92.6%); class 2: individuals with slightly unhealthy diet habits (6.3%); class 3: individuals with relatively unhealthy diet habits (0.8%); and class 4: individuals with unhealthy diet habits (0.2%). Being female and alcohol consumption increased the odds of membership in latent classes 2,3, and 4 compared to class 1. Physical activity decreased the odds of membership in classes 3 and 4 compared to class 1. Conclusion: Overall, almost more than 7.4% of all participants had some degree of unhealthy dietary habits, and some variables acted as risk factors for membership in risky classes. Therefore, focusing on these variables may help design and execute effective preventive interventions in groups with unhealthy dietary habits.

Pattern of body mass index, chronic diseases, and physical component of quality of life in a population in North of Iran: A latent class analysis.

Background: Due to the rise of non-communicable diseases (NCDs) and lifestyle changes, this study aimed at determining the subclasses of Iranian adults based on body mass index, some NCDs, and status of physical component of quality of life. Methods: A total of 5207 participants of Amol cohort study were studied in this study. Latent class analysis (LCA) was used to determine the best model with the minimum AIC or BIC. Results: We decided that the 6 latent classes model was the best model. The first class described 35.1% of the participants and was characterized by individuals with no disease status. The sixth class described 0.7% of the individuals and was characterized by individuals exhibiting high probability of body mass index (BMI) equal or more than 25, kidney inadequacy, hypertension, and moderate physical component of quality of life status. Conclusion: This study showed the pattern of body mass index, chronic diseases, and physical component of quality of life. Our findings demonstrated that some risk factors and non-communicable diseases tend to accumulate in some classes, especially classes 5 and 6, and thus the risk of developing these diseases rises along with increase in their clustering abilities. These results point out the critical importance of designing specific preventive interventional programs for these stratums of individuals.

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.