Effect of Empagliflozin and Pioglitazone on left ventricular function in patients with type two diabetes and nonalcoholic fatty liver disease without established cardiovascular disease: a randomized single-blind clinical trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease. METHODS: This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM). RESULTS: In this study, GLS improved by 1.56 ± 2.34% (P < 0.01) in the pioglitazone group and 1.06 ± 1.83% (P < 0.01) in the empagliflozin group without a significant difference between the two groups (P = 0.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r = - 0.311, P = 0.007. LSM in the pioglitazone and empagliflozin group [(-0.73 ± 1.59) and (-1.11 ± 1.33)] kpa (P < 0.01) decreased significantly. It was without substantial difference between the two groups (P = 0.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22 + 35.02 dB/m vs. -25.67 + 41.50 dB/m, P = 0.01. CONCLUSION: Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations. TRIAL REGISTRATION: This trial was registered in the Iranian Registry of Clinical Trials (IRCT): "A Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease" IRCT20190122042450N5, 29 November 2020. https://www.irct.ir/search/result?query=IRCT20190122042450N5 .

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.

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.

Systems biology approach to identify biomarkers and therapeutic targets for colorectal cancer.

Background: Colorectal cancer (CRC), is the third most prevalent cancer across the globe, and is often detected at advanced stage. Late diagnosis of CRC, leave the chemotherapy and radiotherapy as the main options for the possible treatment of the disease which are associated with severe side effects. In the present study, we seek to explore CRC gene expression data using a systems biology framework to identify potential biomarkers and therapeutic targets for earlier diagnosis and treatment of the disease. Methods: The expression data was retrieved from the gene expression omnibus (GEO). Differential gene expression analysis was conducted using R/Bioconductor package. The PPI network was reconstructed by the STRING. Cystoscope and Gephi software packages were used for visualization and centrality analysis of the PPI network. Clustering analysis of the PPI network was carried out using k-mean algorithm. Gene-set enrichment based on Gene Ontology (GO) and KEGG pathway databases was carried out to identify the biological functions and pathways associated with gene groups. Prognostic value of the selected identified hub genes was examined by survival analysis, using GEPIA. Results: A total of 848 differentially expressed genes were identified. Centrality analysis of the PPI network resulted in identification of 99 hubs genes. Clustering analysis dissected the PPI network into seven interactive modules. While several DEGs and the central genes in each module have already reported to contribute to CRC progression, survival analysis confirmed high expression of central genes, CCNA2, CD44, and ACAN contribute to poor prognosis of CRC patients. In addition, high expression of TUBA8, AMPD3, TRPC1, ARHGAP6, JPH3, DYRK1A and ACTA1 was found to associate with decreased survival rate. Conclusion: Our results identified several genes with high centrality in PPI network that contribute to progression of CRC. The fact that several of the identified genes have already been reported to be relevant to diagnosis and treatment of CRC, other highlighted genes with limited literature information may hold potential to be explored in the context of CRC biomarker and drug target discovery.

Poor Sleep Quality and Its Influencing Factors Among Iranian Patients with Esophageal and Gastric Cancer.

Background: Sleep quality is a notable factor of well-being. It also may play a role in the development and progression of chronic diseases and cancers. Therefore, this study was performed to investigate poor sleep quality and its influencing factors among Iranian patients with esophageal and gastric cancer. Methods: In this cross-sectional study, a total of 312 Iranian adult patients who suffered from esophageal and gastric cancers were employed from a gastrointestinal cancer-based cohort study conducted in a referral hospital in Tehran between 2015 and 2018. Persian version of the Pittsburg Sleep Quality Index (PSQI) was used to measure poor sleep quality. Univariate and multiple logistic regression models were applied to determine the related factors to poor sleep quality. Results: Of the participants, 203 (65.06%) were men, and 75.96% had gastric cancer. The mean age was 63.13±12.10 years. The results demonstrated that more than 62% of the patients had poor sleep quality. 148 (62.44%) patients out of 237 patients with gastric cancer had poor-quality sleep. Also, 46 (64.38%) patients out of 237 patients with esophageal cancer had poor-quality sleep. Based on the results of multiple logistic regression models, marital status has a negative association with poor sleep quality (odds ratio [OR]=0.32, P=0.015). In addition, having chronic disease (OR=2.16; P=0.028) and wealth index (OR=3.11, P=0.013; OR=3.81, P=0.003; OR=3.29, P=0.009; OR=3.85, P=0.003 for rich, moderate, poor, and poorest subgroups, respectively) had a positive association with poor sleep quality. Conclusion: The findings showed that about two-thirds of the patients studied were poor sleepers. Also, it was observed that marital status, chronic disease, and wealth index were important factors associated with poor sleep quality.

Path analysis model to identify the effect of poor diet quality on NAFLD among Iranian adults from Amol Cohort Study.

Nonalcoholic fatty liver disease (NAFLD) is expanding as a global health problem with approximately 25% of the world's population affected by it. Dietary modification is one of the most important strategies for preventing NAFLD. The association between nutrient density and the Healthy Eating Index 2015 (HEI2015) with NAFLD demonstrates that nutrient density is an independent predictor of NAFLD in Iranian adults [fully adjusted model: OR (95% CI)tertile3vs.1: 0.68 (0.54-0.85), P for trend = 0.001]. However, a favorable association between NAFDL and diet quality (HEI 2015) is more pronounced in participants with abdominal obesity [fully adjusted model: OR (95% CI)tertile3vs.1: 0.63 (0.41-0.98), P for trend = 0.03]. Based on the gender-stratified path analysis, diet quality indirectly through Waist-to-Height Ratio (WHtR), C-reactive protein (CRP), and metabolic syndrome in women, and men through WHtR, hemoglobin A1c (HBA1c), CRP, and metabolic syndrome affects NAFLD. Nutrient density directly and indirectly in women through WHtR, CRP, and metabolic syndrome, and in men indirectly through WHtR, hemoglobin A1c, and metabolic syndrome negatively affect NAFLD. Hence, in these subjects; we can provide early dietary intervention and education to prevent progression to NAFLD.

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.

Atypical Presentation of Adult-Onset Still's Disease.

Adult-onset Still's disease (AOSD) is a rare rheumatic disorder with various presentations. It is diagnosed based on the Yamaguchi criteria, besides the exclusion of infectious diseases and other rheumatic disorders and malignancies. Here, we describe a case of a young man, presenting with remittent fever, abdominal pain, and persistent nausea. Further evaluations showed elevated acute phase reactants, abnormal levels of liver transaminase, multiple lymphadenopathies, and pleural effusion. He was finally diagnosed with AOSD and responded well to corticosteroids and methotrexate. We describe the present case to alert gastroenterologists to AOSD as a rare differential diagnosis in patients with persistent gastrointestinal symptoms.

Serum Alkaline Phosphate Level Associates with Metabolic Syndrome Components Regardless of Non-Alcoholic Fatty Liver; A Population-Based Study in Northern Iran.

Background: Serum alkaline phosphatase (ALP) is an indicator of hepatobiliary disorders, such as metabolic syndrome (MetS). To assess the association between serum ALP levels and MetS, with or without non-alcoholic fatty liver disease (NAFLD), in a cohort study in northern Iran. Methods: Data from approximately 5257 subjects aged more than 18 years participating in the Amol cohort were used. We extracted the required data and investigated the correlation between liver enzyme levels and MetS. Multiple logistic regression analyses based on the serum ALP quartiles were performed. Results: Of them, 2860 were male with a mean age of 42.11±16.1 years. A positive linear trend was observed between serum ALP levels and the number of MetS components in both sexes. In both sexes, systolic blood pressure, waist circumferences, and high-density lipoprotein (HDL) had a significant association with ALP. After adjusting for age, both sexes with NAFLD showed an increased risk of developing MetS. The risk of NAFLD increased in individuals with>2nd quartile of ALP. Furthermore, higher ALP levels were associated with an increased risk of MetS in males (1.1014 [0.782-1.315]) and females (1.441 [1.085-1.913]). Conclusion: There is a significant association between serum ALP levels and MetS, independent of fatty liver changes, suggesting that this marker can be considered as a feasible predictor of MetS.

Household Food Insecurity and Associated Factors among Iranian Patients with Esophageal and Gastric Cancers.

Background: Household food insecurity (HFI) which has still been one of the major global public health issues is related to adverse health outcomes in individuals. Therefore, this study aimed to determine the prevalence of HFI and its associated factors in Iranian patients with esophageal and gastric cancers. Methods: The data of this cross-sectional study was obtained from 315 patients with esophageal and gastric cancers who were selected from a gastrointestinal cancer-based cohort study conducted in Firoozgar hospital, in Tehran. Food insecurity (FI) was measured using the Iranian version of the HFI questionnaire that was completed by a trained interviewer. The multivariable logistic regression model was used to determine the independent association of each factor with HFI. A P value lower than 0.05 was considered statistically significant. Results: The mean±SD of participants' age was 63.2±12.6 years and 65.4% were men. Most of the patients (75.8%) suffered from gastric cancer and 24.2% from esophageal cancer. The overall prevalence of FI among participants' households was 35.2%. There was an independent significant association between wealth index (WI) and HFI after the use of the multivariable logistic regression model, in such a way that the odds of FI in the poorest, poor, moderate, and rich patients' households were respectively, 6.41, 5.05, 2.74 and 2.04 times higher compared with the richest households. Conclusion: More than a third of participants' households struggled with FI, which was found to have a higher prevalence in loweconomic households. Therefore, health policymakers should intervene in food-insecure households by developing, establishing, and implementing strategies and control programs to improve affordable food access.

The association between CD3+ and CD8+tumor-infiltrating lymphocytes (TILs) and prognosis in patients with pancreatic adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PDAC), with more than 250,000 deaths each year, is the eighth leading cause of death worldwide, with a five-year survival of less than 5% and a median recurrence time between 5 and 23 months. The association between PDAC and CD3+/CD8+ tumor-infiltrating lymphocytes (TILs) and the extent of tumor spread and clinical outcomes has been recently shown. This study aimed to determine and compare the density of TILs and their association with disease prognosis in patients with PDAC. MATERIALS AND METHODS: In this study, we collected PDAC tissues and corresponding adjacent normal tissues from 64 patients with TIL-positive PDAC. The immunohistochemistry method was used for the detection of the expression levels of CD3+ and CD8+ TILs in PDAC tissues. Also, the completed follow-up history was evaluated for at least five years. RESULTS: The frequency of intratumoral and peritumoral TILs was 20 (31.2%) and 44 (68.8%), respectively. The mean density of CD3+ TILs and CD8+ TILs was 67.73%±20.17% and 69.45%±17.82%, respectively. The density of CD3+ TILs and CD8+ TILs was not associated with overall survival nor metastasis-free survival of the patients and tumor grade. However, the density of TILs was significantly lower in those patients who experienced tumor recurrence than those without this recurrence. CONCLUSION: TILs density was high in patients with PDAC. The density of both CD3+ and CD8+ TILs was significantly lower in patients who experienced tumor recurrence. Thus, this study suggests that tracking and determining the density of CD3+ and CD8+ TILs might be effective in predicting PDAC recurrence.

Cytochrome P2E1 (CYP2E1) Gene Polymorphism as a Potential Prognostic Biomarker in Colorectal Cancer.

BACKGROUND: Colon cancer is the most common type of gastrointestinal cancer. Genetic factors have been shown to have a role in the development of colorectal cancers. The aim of this study was to assess the expression of Cytochrome P2E1 (CYP2E1) gene polymorphism as a potential prognostic biomarker in the diagnosis, treatment, and prognosis evaluation of patients with colorectal cancer. METHODS: in this cross-sectional study, all of our 100 patients with colorectal cancer who underwent surgical operation were included. DNA was extracted from the tumor specimens to assess Cytochrome P2E1 (CYP2E1) Gene polymorphism by Conventional-PCR. RFLP-PCR method was used for RsaI polymorphism evaluation. Patients' characteristics were also recorded and their associations with CYP2E1 were assessed. RESULTS: One hundred tumor specimens were assessed. In total, 88 had wild-type, 8 had purely a 96 bp insertion in CYP2E1, and 4 were partially mutated by a single allele insertion. Generally, 10% of samples had positive results for the RsaI polymorphism. There were no statistically significant associations between CYP2E1 gene polymorphism and number of lymph nodes removed during the operation (P = 0.353), number of positive lymph nodes (P = 0.668), tumor specificity including mucinous or non-mucinous (P = 0.053), tumor invasion (P = 0.074), grading (P = 0.898), differentiation (P = 0.941), tumor location (P = 0.42) or staging (P = 0.182). CONCLUSION: There was no association between RsaI type CYP2E1 polymorphism and colorectal cancer risk. Our study does not support the use of this biomarker to evaluate the prognosis of colon cancer.

Iranian hereditary hemochromatosis patients: baseline characteristics, laboratory data and gene mutations.

BACKGROUND: Hereditary hemochromatosis (HH) is the most common autosomal recessive disorder in white people, characterized by highly abnormal uptake of iron from the gastrointestinal tracts. Recently, mutation studies have focused to detect the genes responsible for HH. MATERIAL/METHODS: In this cross-sectional study, 12 HH patients were recruited, who were referred to Firoozgar Hospital, Tehran, Iran. In addition to the clinical assessments, a complete laboratory evaluation, imaging modalities, histopathologic assessment, atomic absorption spectrophotometry and gene mutation study were performed. The genetic study for HFE gene mutation was examined for all of the patients since 2006, while non-HFE mutation was conducted since December 2010 (only for 1 of them). RESULTS: Twelve patients were evaluated consisting of 11 men and 1 woman, with the mean age of 39.58±12.68 yr. The average of atomic iron loads was 13.25±4.83-fold higher than normal standards. Four patients had heterozygotic mutation of H63D (33.3%). There was no significant difference in either the iron load of liver (P=0.927) and heart (P=0.164) or serum concentration of ferritin (P=0.907) and TIBC (P=0.937) between the HFE-mutant and without HFE mutation HH cases. CONCLUSIONS: In contrast to other studies, C282Y mutation was not detected in any of our Iranian HH patients. Heterozygotic mutations of H63D (HFE) and TFR2 (non-HFE) genes were found to be more common in these patients. Similar to previous reports, these mutations were not found to be significantly associated with severity of presentation in HH patients.

Dynamic Population of Gut Microbiota as an Indicator of Inflammatory Bowel Disease

Background: Inflammatory bowel disease is a chronic inflammatory disease of the gastrointestinal tract. The gut microbiota is an important factor in the pathogenesis of inflammatory bowel disease (IBD). Due to a link between the gut microbiota and IBD, studying microbiota changes using an accurate, sensitive and rapid method for detection of the disease seems necessary. This study aimed to compare the composition of gut microbiota in three groups of people, including IBD patients, cured Inflammatory bowel disease (CIBD), and healthy groups. Methods: For this study, 45 stool samples (15 from each group) were collected. Using real-time PCR, the abundance of 11 bacterial 16S rRNA gene sequences was examined. Results: In the IBD group, the number of three bacterial phyla, including Firmicutes, Actinobacteria, and Bacteroidetes, decreased (p < 0.01, p < 0.01, and p < 0.001, respectively), while the population of γ-Proteobacteria increased significantly (p < 0.0001). In the CIBD group, the number of Actinobacteria enhanced (p < 0.01), but that of Bacteroidetes and Firmicutes decreased (p < 0.01, and p < 0.05, respectively). Conclusion: Findings of this study indicate that decrease in Firmicutes and increase in γ-Proteobacteria could be used as an indicator of IBD instead of employing invasive and costly detection methods such as colonoscopy and other tests.

Association between Melatonin Value and Interleukins1B, -18, and -33 Levels in Patients with Different Stages of Non-Alcoholic Fatty Liver Disease.

BACKGROUND: Interaction between immune modulators and inflammatory factors is considered as one of the main underlying pathologies of non-alcoholic fatty liver disease (NAFLD). Hence we aimed to assess the association between these cytokines and melatonin. METHODS: We enrolled adult patients diagnosed with fatty liver by ultrasonography in a crosssectional study. All of them underwent Fibroscan evaluation. The subjects who met the inclusion and exclusion criteria for NAFLD were involved. A normal group who did not have NAFLD, viral or non-viral hepatitis, and without a history of pancreatobiliary surgery, bariatric surgery, and intake of any medication that influence the liver was also selected. The participants were categorized into the three following groups: 1) fibrosis>9.1 kPa and steatosis>290 dbm, 2) fibrosis: 6-9.0 kPa and steatosis 240-290 dbm, and 3) normal group with fibrosis<6.0 kPa and steatosis<240 dbm. Laboratory assessment and a questionnaire including demographic, anthropometric, laboratories, and clinical data were completed for each of them. RESULTS: Totally 97 subjects were enrolled in the present study. The mean age of the subjects was 42.2±11.3 years. 60% of them (59 patients) were female. Serum levels of melatonin, interleukin (IL)-1B, IL-18, and IL-33 increased according to the advancing of NAFLD state. Based on multiple linear regression model, melatonin was significantly associated with IL-1B (ß=2.8, P<0.001,95% CI=1.41-4.19), IL-18 (ß=0.018, P=0.0005, 95% CI=0.006-0.03), and IL-33 (ß=0.31, P=0.045, 95% CI=0.008-0.62) after adjustment for other variables. CONCLUSION: Melatonin level has a strong association with these cytokines. This linkage probably influences on the development and progression of NAFLD. Therefore it can be hypothesized that the therapeutic approach that affects this process may have a significant impact.

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.

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.

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.

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].

Scoring systems of metabolic syndrome and prediction of cardiovascular events: A population based cohort study.

BACKGROUND AND AIMS: Continuous scoring systems were developed versus traditional dichotomous approaches to define metabolic syndrome. The current study was carried out to evaluate the ability of scoring systems to predict fatal and nonfatal cardiovascular events. MATERIALS AND METHODS: The data of 5147 individuals aged 18 years or more obtained from a population-based cohort study were analyzed. The occurrence of atherosclerotic cardiovascular disease (ASCVD) in the period of 7 years follow-up was considered as the associated outcome. Joint Interim Statement (JIS) definition, as a traditional definition of metabolic syndrome (MetS), and two versions of MetS scoring systems, based on standardized regression weights from structural equation modeling (SEM) and simple method for quantifying metabolic syndrome (siMS) were considered as potential predictors. RESULTS: The scoring systems, particularly, based on SEM, were observed to have a significant association with composite cardiovascular events (HR = 1.388 [95% CI = 1.153-1.670], p = .001 in men and HR = 1.307 [0.95% CI = 1.120-1.526] in women) in multiple Cox proportional hazard regression analyses, whereas the traditional definition of MetS did not show any significant association. While both two scoring systems showed acceptable predictive abilities for cardiovascular events in women (MetS score based on SEM: area of under curve [AUC] = 0.7438 [95% CI = 0.6195-0.7903] and siMS: AUC = 0.7207 [95% CI = 0.6676-0.7738]), the two systems were not acceptable for identifying risk in men. CONCLUSION: Unlike the dichotomous definition of MetS, the scoring systems showed an independent association with cardiovascular events. Scoring systems, particularly those based on SEM, may be useful for the prediction of cardiovascular events in women.