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Background: The relationship between kidney and vascular health is acknowledged, but detailed information is still missing. This study examines the relationship of estimated glomerular filtration rate (eGFR) and carotid intima media thickness, providing insights into the association between atherosclerosis and kidney function., Methods: Participants older than 50 years of age who were part of the PolyIran-L study, a trial nested in the Golestan Cohort Study, were included. The maximal intima media thickness of both common carotid arteries was evaluated using B-mode ultrasonography. Four different cut-off values for abnormal carotid intima media thickness were considered. Correlation of carotid intima media thickness and eGFR was assessed with linear correlation and multivariable binary logistic regression models after adjusting for several confounders., Results: In total, 1562 participants (750 females, 48%) were included in this population-based study. Assuming the eGFR < 45 [mL/min/1.73 m 2 ] group as reference in the crude analysis, those with eGFR ≥ 45 and < 60 [mL/min/1.73 m 2 ] showed an association of being less likely to have carotid intima media thickness above the 0.8 cutoff. However, the fully adjusted analysis showed no significant statistical association between carotid intima media thickness and eGFR., Conclusion: This study did not support the independent association of eGFR and different carotid intima media thickness cutoffs. This pattern may be different in patients with severely decreased eGFR, a subset of cases in which it should be further investigated., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: While cardiovascular disease (CVD) polypills have demonstrated significant benefits in preventing CVD events by managing CVD risk factors and improving patient adherence, their effects on blood glucose levels, an important risk factor for CVD, remain unknown., Methods: We analyzed data from the PolyIran-Liver trial, which involved 1,508 participants aged 50 and above. Of these, 787 were randomly assigned to receive a polypill (consisting of aspirin, atorvastatin, hydrochlorothiazide, and valsartan), while 721 received usual care as the control group over a five-year period. The aim was to determine whether there were any significant differences in fasting blood sugar (FBS) levels between the two groups at baseline, middle, and end of the study. The data analysis focused on three subgroups: participants with diabetes, those with metabolic syndrome (MetS) but without diabetes, and participants without diabetes or MetS., Results: Of the total studied population, with a mean age of 59±6.7 years, 328(22%) were identified with diabetes, 371 (25%) with MetS but without diabetes, and 809 (54%) without diabetes or MetS. We observed a trend of rising FBS levels until month 30, followed by a subsequent decline at month 60. Participants in the polypill group exhibited lower FBS levels than the control group at both time points, with statistically significant differences in all three subgroups at month 30 and in the MetS-without diabetes at month 60 (mean difference: -9.3 mg/dl, 95% CI: 13.9 to -4.6)., Conclusion: The polypill used in this study may have the potential to delay the onset of diabetes in patients with MetS more effectively than in the general population. However, its beneficial effects on the blood sugar levels of diabetic individuals require further investigation., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a rising global public health concern. It has been demonstrated that its prevalence and characteristics vary by region and racial/ethnicity. We aimed to investigate the prevalence of MAFLD and its characteristics among Turkmen and non-Turkmen ethnic groups in a multiethnic population region of Iran., Methods: In this cross-sectional study, we analyzed baseline data for 1614 participants, aged above 50 years, from the PolyIran-Liver trial who were randomly selected from Gonabad city and determined the prevalence of MAFLD and its demographic and metabolic disorders for both the Turkmen and non-Turkmen ethnic groups. Multivariate binary logistic regressions were applied to identify MAFLD-associated factors for men and women separately for the Turkmen and non-Turkmen populations., Results: The mean (SD) age of the participants was 59.1(6.7) years. Of the participants, 51.5% (n=831) were men, and 52.9% (n=854) were Turkmen. The prevalence of MAFLD among the overall study population was 39.8% (n=614). It was more common among women (45.8% vs. 34.1% in men, P <0.001), non-Turkmens (43.9% vs. 36.1% in Turkmens, P <0.001), and at age 50-64 (41.5% vs.36.1% in age≥65 P =0.004). The fully adjusted multivariate analysis in sex strata exhibited an independent negative association between Turkmen ethnicity only among men but not among women. The increased waist circumference (WC) was the most common metabolic disorder, observed in more than 95.5% of patients with MAFLD ( P <0.001). Multivariate analysis in sex/ethnic strata with adjustment for potential confounders revealed an independent association of MAFLD with increased WC, insulin resistance, impaired fasting glucose/diabetes type 2, and high alanine aminotransferase (ALT) among women in both ethnic groups while with elevated triglyceride (TG) only among Turkmen and high body mass index (BMI) only among non-Turkmen women. Increased WC had the strongest independent association with MAFLD among women and the highest odds ratio (OR) with MAFLD in Turkmen women (OR: 6.10; 95% CI 1.56-23.86 vs. 4.80 in non-Turkmen women). Among men, MAFLD was independently associated with insulin resistance, high BMI, and high ALT in both ethnic groups and elevated TG only in non-Turkmen men (all P <0.001). Insulin resistance had the strongest independent OR with MAFLD among men with similar size in both ethnic groups (4.68 [95% CI 2.56-8.55]) in non-Turkmen men and 4.37 (95% CI 2.27-8.42 in Turkmen men)., Conclusion: This study revealed the high prevalence of MAFLD with a sex and ethnic disparity in the middle-aged population of Gonabad city. Further research is needed to understand the factors contributing to the higher prevalence of MAFLD in this region, particularly in women. Furthermore, considering the diverse ethnic population of Iran, it is suggested that future investigations on the sex and ethnic aspects of MAFLD in the Iranian population be conducted to provide targeted prevention strategies better suited for the Iranian population., Competing Interests: Competing Interests The authors declare no conflict of interest related to this work., (© 2024 Middle East Journal of Digestive Diseases.)

Background: Sofosbuvir (SOF) is a revolutionary treatment for patients with hepatitis C virus (HCV). However, its efficacy and safety among patients with end-stage renal disease (ESRD) remains controversial. In this study, we examined the levels of SOF metabolite (GS-331007) (SOF-007) in human plasma of patients infected with HCV having ESRD using an optimized liquid chromatography-mass spectrometry (LC-MS) analytical method., Methods: In this case-control study, 10 clinically confirmed cases and five controls were enrolled. SOF-007 was extracted from plasma using methanol precipitation. The limit of detection (LOD) for the drug and its metabolite were 0.85 and 2.3, respectively. Such a wide range of quantification in a period of separation time shorter than 3.0 minutes (run time) allowed monitoring of the plasma concentration of analytes up to 4 hours (pre-dialysis and post-dialysis) for 12 weeks in non-cirrhotic patients with HCV infection undergoing dialysis., Results: SOF-007 in the plasma of HCV patients with healthy kidneys showed no cumulative effect. An analysis comparing patients with ESRD and healthy participants showed that their behaviour was similar, followed by dialysis with a relatively small cumulative effect., Conclusion: The plasma concentrations of SOF-007 decreased significantly after the 4-hour period of dialysis compared with the plasma concentrations hemodialysis of pre-dialysis in HCV patients with ESRD., Competing Interests: Competing Interests The authors declare no conflict of interest related to this work., (© 2024 Middle East Journal of Digestive Diseases.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel term that distinguishes patients at risk of adverse clinical outcomes with higher accuracy than those with non-alcoholic fatty liver disease (NAFLD). Cardiovascular mortality is the leading cause of death in MAFLD. The current literature lacks large-scale prospective studies that address preventive approaches for cardiovascular health in MAFLD. We investigated whether MAFLD patients benefit from a fixed-dose combination therapy (Aspirin, hydrochlorothiazide, atorvastatin, valsartan), known as a Polypill., Methods: Analysis was performed (stratified based on MAFLD status) of a clinical trial that included 1596 individuals randomly allocated to an intervention (polypill) or a control (usual care) group. Patients were followed up for five years for any adverse drug reaction, major cardiovascular events, and mortality. Univariable and multivariable survival analyses were performed, and the interaction level was assessed by R programming., Results: Patients who consumed the polypill had significantly lower hazard ratios of major cardiovascular events incidence (HR 0.56, 95% CI 0.41-0.78) and cardiovascular mortality (HR 0.41, 95% CI 0.2-0.86) compared to the control group. Polypill showed significantly better results in lowering cardiovascular events in MAFLD patients than in the general population. (p-value for interaction: 0.028). Moreover, comparing those patients who had high adherence to the Polypill, with the control group, further enhanced the results., Conclusions: Major cardiovascular events are prevented in MAFLD patients who consume the Polypill. MAFLD patients benefit from the Polypill more than the general population., (© 2023. Asian Pacific Association for the Study of the Liver.)

Background: and study aims: Gastrointestinal microbiota are closely related to the pathogenesis of ulcerative colitis (UC). This study aimed at quantification of F. prausnitzii, Provetella, and Peptostreptococcus in UC and non-UC patients using Real-Time PCR and a new set of primers were also validated for this purpose., Materials and Methods: In this study, the relative abundance of microbial populations between the UC and non-UC subjects were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). DNA extraction from biopsies and polymerase chain reaction (PCR) amplification of bacterial 16S rRNA gene-targeted species-specific primers was performed to detect the anaerobic bacterial species. The qRT-PCR was used to show the relative change in the bacterial populations of F. prausnitzii, Provetella, and Peptostreptococcus in the UC and non-UC subjects., Results: Our data for detection of the anaerobic intestinal flora showed Faecalibacterium prausnitzii, Provetella and Peptostreptococcus were the predominant microflora in the controls and showed significant differences (p = 0.002, 0.025 and 0.039, respectively). The qRT-PCR analyses of F. prausnitzii, Provetella and Peptostreptococcus were 8.69-, 9.38- and 5.77-higher, respectively, in the control group than in the UC group., Conclusion: The results of this study showed decreased abundance of F. prausnitzii, Provetella and Peptostreptococcus in the intestine of UC patients in comparison to non-UC patients. Quantitative RT-PCR, as a progressive and sensitive method, could be useful for evaluation of bacterial populations in patients with inflammatory bowel diseases to attain appropriate therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests in this study., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: In the absence of head-to-head clinical trials, indirect comparative studies are needed to help position therapies in ulcerative colitis (UC). We aimed to compare the efficacy of infliximab vs. tofacitinib for moderate-severe UC among biologic-naïve participants at post-induction., Methods: This was a post-hoc analysis of patient-level data from four clinical trials including 659 biologic-naïve UC participants. We compared proportions of patients achieving week 8 clinical remission (CR), endoscopic improvement, and endoscopic remission. Clinical response at week 2 was also assessed. Multiple logistic regression models were adjusted for potential confounders identified as having an association with the outcome of interest on univariate analysis. Propensity scores were calculated to create a cohort of participants with similar distribution of baseline co-variates., Results: Patients treated with infliximab had significantly greater odds of CR at week 8 compared to tofacitinib [88/242 (36.4%) vs. 100/417 (24.0%), aOR: 1.65 (95% CI 1.11-2.44), p = 0.013]. Endoscopic improvement at week 8 was also significantly greater among infliximab-treated patients [149/242 (61.6%) vs. 159/417 (38.1%), aOR: 2.12 (95% CI 1.45-3.10), p < 0.001]. Similar findings were observed with week 8 endoscopic remission [61/242 (25.2%) vs. 43/417 (10.3%); aOR: 2.72 (95% CI 1.66-4.46), p < 0.001]. A similar proportion of participants attained clinical response at week 2 [205/242 (84.7%) vs. 334/417 (80.1%), aOR: 1.48 (95% CI 0.93-2.37), p = 0.101]. Similar results were observed among the propensity score matched cohort., Conclusion: Based on the efficacy observed in this post-hoc analysis, consideration should be given to use of infliximab over tofacitinib for treatment of moderate to severe biologic-naïve UC. However, baseline characteristic mismatches persisted despite propensity score matching, and further studies are needed to confirm our findings., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The endoscopic scoring of ulcerative colitis is routinely used for both individual patient management and as an endpoint in clinical trials. The most commonly used scoring system is the Mayo endoscopic subscore, which scores endoscopic disease activity on a scale between 0 and 3. With only four possible scores and consideration of only the most involved area of the colon, the Mayo endoscopic subscore lacks sensitivity to change in measuring the totality of the endoscopic inflammatory involvement in patients with ulcerative colitis. Here, we present one case study from clinical practice and one from clinical trials in which using the Mayo endoscopic score leads to potentially incorrect conclusions. Further, in a post-hoc analysis, we re-examined endoscopic videos from a clinical trial and demonstrate that assessing involved ulcerated and affected areas on a segmental level of the colon or summing Mayo scores of colonic segments can identify improvements in endoscopic disease activity in almost twice as many subjects as identified by the Mayo endoscopic subscore alone. Although the alternative scoring systems we have used in this report will need further validation, our findings demonstrate the need for a more sensitive endoscopic scoring system in ulcerative colitis., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The main composition of intestinal microbiota in nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) patients has not yet been elucidated. In this, case-control study, we identified differences of intestinal microbiota in male patients with NAFLD, presumed NASH, and healthy controls., Materials and Methods: We compared gut microbial composition of 25 patients with NAFLD, 13 patients with presumed NASH, and 12 healthy controls. Demographic information as well as clinical, nutritional, and physical activity data was gathered. Stool and blood samples were collected to perform the laboratory analysis. The taxonomic composition of gut microbiota was assessed using V4 regions of microbial small subunit ribosomal Ribonucleic acid genes sequencing of stool samples., Results: Firmicutes, Actinobacteria, and Bacteroidetes were the most frequently phyla in all groups. Our results revealed that Veillonella was the only genus with significantly different amounts in presumed NASH patients compared with patients with NAFLD ( P = 2.76 × 10 -6 , q = 2.07 × 10 -4 , logFC = 5.52)., Conclusion: This pilot study was the first study to compare gut microbial composition in patients with NAFLD and presumed NASH in the Middle East. Given the potential effects of gut microbiota on the management and prevention of NAFLD, larger, prospective studies are recommended to confirm this study's findings., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Research in Medical Sciences.)

Aims: Individuals with non-alcoholic steatohepatitis or elevated liver enzymes have increased cardiovascular mortality but are often excluded from prevention trials. We investigated the effectiveness of fixed-dose combination therapy for the prevention of major cardiovascular events (MCVE) among individuals with and without presumed non-alcoholic steatohepatitis (pNASH)., Methods and Results: Two thousand four hundred participants over 50 were randomized into the intervention and control groups. Consent was obtained post-randomization. Consenting participants in the intervention group were given a pill containing aspirin, atorvastatin, hydrochlorothiazide, and valsartan (polypill). Participants were followed for 5 years. Presumed non-alcoholic steatohepatitis was diagnosed by ultrasonography and elevated liver enzymes. The primary outcome was MCVE. ClinicalTrials.gov: NCT01245608. Among the originally randomized population, 138 of 1249 in the intervention group (11.0%) and 137 of 1017 controls (13.5%) had MCVE during the 5-year follow-up [unadjusted risk ratio (RR) 0.83, 95% confidence interval (CI) 0.66-1.03]. Of the 1508 participants who consented to additional measurements and treatment, 63 of 787 (8.0%) intervention group participants and 86 of 721 (11.9%) controls had MCVE (adjusted RR 0.61, 95% CI 0.44-0.83). Although the adjusted relative risk of MCVE in participants with pNASH (0.35, 95% CI 0.17-0.74) was under half that for participants without pNASH (0.73, 95% CI 0.49-1.00), the difference did not reach statistical significance. There was no change in liver enzymes in participants taking polypill but among those with pNASH, there was a significant decrease after 60 months of follow-up (intragroup -12.0 IU/L, 95% CI -14.2 to -9.6)., Conclusion: Among patients consenting to receive fixed-dose combination therapy, polypill is safe and effective for the prevention of MCVE, even among participants with fatty liver and increased liver enzymes., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Disruptions in sleep related to mealtime may contribute to gut microbial imbalances, and put individuals at higher risk for metabolic diseases. The aim of this pilot study was to investigate the relationships between late-night eating habits and sleep quality and duration, with gut microbiota (GM) profiles., Methods: In this cross-sectional study, 36 men referred to a clinic were enrolled. In addition to demographic information, each participant completed questionnaires regarding medical history, physical activity, late-night eating habits, sleep quality and sleep duration. The scores from these questionnaires were used to categorize study participants into the following groups: sleep quality (good or poor), late-night eating (yes or no) and sleep duration (<7 or ≥7 hours). Five grams of stool was also obtained from each participant for GM profiling analysis by sequencing., Results: The mean age of the study population was 42.1 ± 1.6 years. Firmicutes and Actinobacteria were the two dominant phyla present in all participant samples. Differences in the relative abundance of GM at each taxonomic rank between study groups were insignificant. Only Erysipelotrichales at the order level were found to be significantly different between individuals who had late-night eating habits and those who did not ( P & q < 0.05). No other parameter demonstrated a significant difference in GM profiles of participants., Conclusion: In this pilot study, we found Erysipelotrichales to be more abundant in individuals with late-night eating habits. Studies with higher sample sizes are warranted to better delineate the possible effects of time of eating on microbial composition., (© 2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: While hepatitis B virus (HBV) is the most prevalent cause of adult liver transplants in Iran, the mortality rates and leading causes of death in HBV patients are not well-understood. This study aimed to investigate all-cause and cause-specific mortality among HBsAg positive individuals in a large Iranian cohort., Methods: The Golestan Cohort Study includes 50045 individuals aged 40-75 residing in Iran's Golestan province, enrolled during 2004-2008. HBsAg test was performed at baseline. For the present study, individuals with hepatitis C coinfection were excluded. All-cause mortality was considered as the primary outcome. The association between HBsAg and different mortality causes was evaluated using Cox proportional hazard models. P value<0.05 was considered significant., Results: The current study included 49667 participants. After 11.33 (median) follow-up years, there were 7,686 total deaths, with 635 deaths in the HBsAg positive group. In the multivariate Cox proportional hazard model, HBsAg positive individuals had higher all-cause (adjusted hazard ratio [aHR]=1.15, 95% CI: 1.06-1.24) and liver-related mortality risk (aHR=7.13; 5.19-9.79). Mortality from colorectal and pancreatic cancers was higher among male HBsAg positive participants (aHRs=2.41 and 2.22, respectively). Nevertheless, cardiovascular diseases (CVDs) and extrahepatic malignancies were the leading causes of death among both HBsAg positive and negative individuals, and liver-related deaths contributed to an overall 10% of deaths in HBsAg positive patients., Conclusion: HBV is associated with significant mortality risk from different causes in Iranian adults. However, solely focusing on liver outcomes in Iranian HBV patients might result in overlooking non-liver events, especially CVD and extrahepatic cancers., (2022 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19., Methods: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1., Results: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality., Conclusions: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Iran is among countries with high opioid agonist therapy (OAT) coverage in prisons, which provides an infrastructure to increase feasibility of HCV programs. We aimed to evaluate the impact of an intervention to improve HCV screening, diagnosis, and treatment, including alongside the provision of OAT, in an Iranian prison., Methods: During July-December 2018, in the Gorgan prison, all incarcerated adults (>18 years) received HCV antibody rapid testing and, if positive, provided a venepuncture sample for HCV RNA testing. Participants with positive RNA received direct-acting antiviral (DAA) therapy [(Sofosbuvir/Daclatasvir) for 24 or 12 weeks, respectively, for those with and without cirrhosis]. Response to treatment was measured by the sustained virological response at 12 weeks post-treatment (SVR12)., Results: Among 2015 incarcerated people with a median age of 35 years (IQR:29-41), the majority were male (97%), had not finished high school (68%), and had a history of drug use (71%), of whom 15% had ever injected drugs. A third of participants were receiving OAT, including 54% of those who had ever injected. HCV antibody prevalence was 6.7%, and RNA was detected in 4.6% of all participants; this prevalence was 32.6% and 24.7% among those with a history of injection, respectively. Treatment uptake was 82% (75/92) and was similar among people on OAT and those with a history of injection (81%). The majority completed treatment in prison and were available for SVR12 assessment (71%, 53/75). Achieved SVR12 was 100% (53/53) based on the available case analysis; those who did not have available SVR12 were released either prior to treatment initiation or completion (n = 39)., Conclusion: The availability of OAT infrastructure should be considered as an opportunity for enhancing HCV care in prisons. Where resources are limited, the prison harm reduction network could be used to design targeted HCV programs among people who are at higher risk of infection., Competing Interests: Declarations of Interest SM is a stockholder of Rojan Pharma and has received travel grants from this company. HP and RM were stockholders of Rojan Pharma but they sold their stocks in early 2019., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The current recommendation for treating hepatitis C virus (HCV) in HIV patients includes the combination of sofosbuvir (SOF) and daclatasvir (DCV). DCV should be used at different doses to compensate for interactions with antiretroviral therapy (ART). Up to three pills a day might be required which will significantly add to the pill burden of these patients. In this study, we have used a single-tablet approach to treating HCV-HIV coinfection., Methods: Patients coinfected with HIV and HCV were prospectively enrolled from 10 centers throughout the country. Patients received a single once-daily fixed dose combination (FDC) pill containing 400 mg SOF and 30, 60 or 90 mg DCV depending on the type of ART they were receiving for 12 or 24 weeks. (ClinicalTrials.gov ID: NCT03369327)., Results: Two hundred thirty-three patients were enrolled from 10 centers. Twenty-three patients were lost to follow-up and two patients died from causes unrelated to treatment. Two hundred eight patients completed the treatment course of which 201 achieved SVR (96.6%)., Conclusion: Single-tablet combination of DCV and SOF is an effective and safe treatment for patients coinfected with HIV and HCV. The combination works well in patients on ART in which dose adjustment is required. Patients with cirrhosis, previous treatment failure and various genotypes respond identically. The expenses of genotyping can be saved., (© 2021 John Wiley & Sons Ltd.)

Introduction: Nonalcoholic fatty liver disease (NAFLD), as the most common liver disease in the world, can range from simple steatosis to steatohepatitis. We evaluated the association between meat consumption and risk of NAFLD in the Golestan Cohort Study (GCS)., Methods: The GCS enrolled 50,045 participants, aged 40-75 years in Iran. Dietary information was collected using a 116-item semiquantitative food frequency questionnaire at baseline (2004-2008). A random sample of 1,612 cohort members participated in a liver-focused study in 2011. NAFLD was ascertained through ultrasound. Total red meat consumption and total white meat consumption were categorized into quartiles based on the GCS population, with the first quartile as the referent group. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: The median intake of total red meat was 17 and total white meat was 53 g/d. During follow-up, 505 individuals (37.7%) were diagnosed with NAFLD, and 124 of them (9.2%) had elevated alanine transaminase. High total red meat consumption (ORQ4 vs Q1 = 1.59, 95% CI = 1.06-2.38, P trend = 0.03) and organ meat consumption (ORQ4 vs Q1 = 1.70, 95% CI = 1.19-2.44, P trend = 0.003) were associated with NAFLD. Total white meat, chicken, or fish consumption did not show significant associations with NAFLD., Discussion: In this population with low consumption of red meat, individuals in the highest group of red meat intake were at increased odds of NAFLD. Furthermore, this is the first study to show an association between organ meat consumption and NAFLD (see Visual Abstract, http://links.lww.com/AJG/B944)., (Copyright © 2021 by The American College of Gastroenterology.)

Introduction and Objectives: After successful treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs), the stage of liver fibrosis decreases over time. Here, we aimed to assess the changes in the liver fibrosis stage using transient elastography (TE) after successful DAA therapy in HCV-infected cirrhotic patients who were referred to Shariati hospital from 2016 to 2017., Material and Methods: In this observational cohort, all HCV-infected cirrhotic patients who were treated with a combination of sofosbuvir/daclatasvir, had sustained virologic response (SVR), and had undergone pre- and post-treatment TE, were enrolled. The primary outcome was the changes in TE parameters six months after the end of treatment compared with baseline., Results: A total of 442 eligible subjects received DAA therapy. Overall, the SVR rate was 96.6%. Of these, 149 patients had completed the protocol and were enrolled. The mean age of patients was 56.1 ± 10.3 years and the predominant sex was male (77.9%). The median (Q 1 -Q 3 ) liver stiffness (LS) value at baseline was 26.3 kPa (18.1-38 kPa), which significantly decreased to 20.9 kPa (12-29.7 kPa) [z = -8.45, P-value < .001]. Also, the liver steatosis of patients with baseline CAP ≥ 220 dB/m had a significant response to treatment [z = -2.3, P-value = .023]. Based on multivariate analysis, a higher baseline liver fibrosis stage was the only determinant of LS values improvement in our study., Conclusion: Successful HCV eradication in patients with liver fibrosis results in significant improvement in LS, even in cirrhotic patients., (© 2021 John Wiley & Sons Ltd.)

BMI does not reflect the location or amount of body fat. We aimed to investigate the role of general and central obesity measures in the prediction of incident gastrointestinal cancers. In this analysis of the Golestan Cohort Study, we included 47 586 cancer-free individuals followed for 12.3 years (IQR: 10.5-13.2). We investigated the association of obesity measures including BMI, waist circumference and waist-to-hip ratio (WHR) at enrollment and the incidence of esophageal, gastric, colorectal and pancreatic cancers. Cox proportional hazard models were used to estimate the association between covariates and gastrointestinal cancer risk. We observed no significant associations between obesity measures and incidence of the above-mentioned gastrointestinal cancers in men. In women, BMI, waist circumference and WHR were associated with significant reductions in the risk of esophageal squamous cell carcinoma (ESCC): hazard ratio (HR): 0.67 [95% confidence interval (CI): 0.56-0.81], HR: 0.71 (95% CI: 0.60-0.84) and HR: 0.80 (95% CI: 0.68- 0.94), respectively. In addition, WHR was associated with significantly increased risks for colorectal cancer (HR: 1.39, 95% CI: 1.08-1.78) and gastric cancer (HR: 1.24, 95% CI: 1.01-1.51) in women. In this study, statistically significant associations between obesity measures and incident esophageal, gastric and colorectal cancers were seen in women., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Familial adenomatous polyposis (FAP) as a colon cancer predisposition syndrome is an autosomal-dominant inherited condition and is diagnosed by the progress of hundreds or thousands of adenomatous colonic polyps in the colon. This study aims at the nature and effect of Adenomatous Polyposis Coli (APC) gene mutations in FAP tumorigenesis., Methods: The genetic screening of 59 FAP Iranian patients in 10 families was performed by polymerase chain reactions and the direct sequencing of the entire coding exons of the APC gene. To do linkage haplotype analysis and multiplex PCR-based microsatellite examination, six short tandem repeat loci were selected in this gene. To evaluate and predict the potentially deleterious effects, comprehensive bioinformatics pathogenicity assays were used., Results: A total of 12 germline heterozygous and homozygous nucleotide variations were identified. They included two missense mutations, four nonsense mutations, which would lead to the truncated and nonfunctional protein products, four synonymous or silent variations, and two nucleotide deletions of 1 to 5 bp or frameshift mutations. In addition, three novel heterozygous nonsense mutations were found in exons 10, 14, and 15 of the gene. There was also p.Arg653Met as a novel heterozygote mutation in exon 14 of the gene., Conclusions: Bioinformatics analysis and three-dimensional structural modeling predicted that these missense and nonsense mutations generally are associated with the deleted or truncated domains of APC and have functional importance and mainly affected the APC protein. These findings may provide evidence for the progress of potential biomarkers and help to understand the role of the APC gene in FAP., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Introduction: Despite being originally developed for the evaluation of lumbar disk degeneration, the Pfirrmann classification has emerged as the most popular classification system for cervical disk degeneration. However, with the Suzuki classification, a new classification system that is specifically tailored for the evaluation of cervical disk disease was introduced. In this study, we aim to evaluate differences in inter- and intraobserver reliability of both classifications in a head-to-head comparison., Methods: In total, we have evaluated 120 cervical disks within 40 patients via magnetic resonance imaging according to the Pfirrmann and Suzuki classification. The degree of disk degeneration was evaluated by two independent musculoskeletal radiologists. After 6 months, the classification was reassessed to evaluate the intraobserver reliability. The inter- and intraobserver reliabilities were then calculated using Cohen's kappa., Results: The inter- and intraobserver reliability provided a significant agreement between all ratings in Pfirrmann as well as the Suzuki classification (p>0.001). The interobserver reliability was determined to be fair in both the Suzuki classification (κ=0.290) and the Pfirrmann classification (κ=0.265). The intraobserver reliability was substantial in the Suzuki classification (κ=0.798), while it was almost perfect in the Pfirrmann classification (κ=0.858)., Conclusions: Although not designed for the evaluation of cervical disk degeneration, the Pfirrmann classification yielded equal inter- and higher intraobserver reliability. Both classification systems are viable options for the grading of cervical disk degeneration. While the Pfirrmann classification has the advantage of being better established, the Suzuki classification may be clinically superior due to a better representation of cervical disk degeneration and the consideration of disk bulging for the classification of cervical disk degeneration., Competing Interests: Conflicts of Interest: The authors declare that there are no relevant conflicts of interest., (Copyright © 2021 by The Japanese Society for Spine Surgery and Related Research.)

Background: Non-alcoholic fatty liver disease (NAFLD) is much more frequent and more severe, including cirrhosis, hepatocellular carcinoma in patients with type 2 diabetes. Coffee is a complex beverage with hundreds of compounds whereas caffeine and chlorogenic acid are the most abundant bioactive compounds. The published epidemiological data demonstrating beneficial associations between all categories of coffee exposure and ranges of liver outcomes are rapidly growing; however, the main contributors and cause-effect relationships have not yet been elucidated. To address existing knowledge gaps, we sought to determine the efficacy and safety of 6 months chlorogenic acid and/or caffeine supplementation in patients with type 2 diabetes affected by NAFLD., Methods: This trial was carried out at two Diabetes Centers to assess the effects of supplementation with daily doses of 200 mg chlorogenic acid, 200 mg caffeine, 200 mg chlorogenic acid plus 200 mg caffeine or placebo (starch) in patients with type 2 diabetes and NAFLD. The primary endpoint was reduction of hepatic fat and stiffness measured by FibroScan, and changes in serum hepatic enzymes and cytokeratin - 18 (CK-18) levels. Secondary endpoints were improvements in metabolic (including fasting glucose, homeostasis model assessment-estimated insulin resistance (HOMA-IR), hemoglobin A1c (HBA1C), C-peptide, insulin and lipid profiles) and inflammatory (including nuclear factor k-B (NF-KB), tumor necrosis factor (TNF-α), high sensitive- C reactive protein(hs-CRP)) parameters from baseline to the end of treatment., Results: Neither chlorogenic acid nor caffeine was superior to placebo in attenuation of the hepatic fat and stiffness and other hepatic outcomes in patients with diabetes and NAFLD. Except for the lower level of total cholesterol in caffeine group (p = 0.04), and higher level of insulin in chlorogenic acid plus caffeine group (p = 0.01) compared with placebo, there were no significant differences among the treatment groups., Conclusion: These findings do not recommend caffeine and/or chlorogenic acid to treat NAFLD in type 2 diabetes patients., Trial Registration: IRCT201707024010N21 . Registered 14 September 2017.

BACKGROUND Hepatitis B and C virus (HBV and HCV) infections rank among the most frequent infectious diseases with a rising worldwide burden. However, their epidemiology and risk factors are understudied in many regions, including Iran. METHODS This study was conducted as part of the Pars Cohort Study (PCS) in Valashahr district, Fars province (2012-2014). Participants received venipuncture for HBsAg and HCV antibody, followed by Polymerase Chain Reaction (PCR) testing. All infected people and their comparison groups completed a risk assessment questionnaire. RESULTS Overall, 9,269 people participated in the study; the majority were women and of Fars ethnicity. Prevalence of HBsAg and HCV antibody was 2.3% (n = 215) and 0.3% (n = 26), from whom 23% (n = 47) and 13% (n = 3) had indications for treatment, respectively. During follow-up, among HBsAg-positive individuals who were not on treatment, 62% tested negative for HBsAg, and in 2% HBV DNA had risen to treatment levels. Risk factors for HBV infection were illiteracy [OR = 3.43, 95% CI = 1.1, 10.3], and Turk ethnicity compared to Fars [OR = 1.58, 95% CI = 1.1, 2.3]. History of blood transfusion [OR = 2.00, 95% CI = 1.1, 3.5] and history of drug use [OR = 2.85, 95% CI = 1.1, 7.4] were associated with HCV infection, after adjustment. CONCLUSION Further epidemiological studies are needed to identify at-risk populations in different regions. Preventive interventions, including educational programs and transfusion safety strategies, are crucial for reducing the hepatitis burden., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest related to this work., (© 2021 The Author(s).)

We examined the impact of chronic prostatitis on the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI). In this retrospective study, 63 men underwent 3T mpMRI followed by MRI/ultrasound fusion biopsy to exclude/confirm clinically significant prostate cancer (csPCa). A total of 93 lesions were included for evaluation. Images were assessed by two radiologists. Prostatitis was graded visually on T2-weighted and contrast-enhanced sequences. The correlation of prostatitis features with the assigned Prostate Imaging Reporting and Data System (PI-RADS) and the presence of csPCa were assessed, and the clinical and functional imaging parameters for differentiating between prostatitis and significant tumors were examined. Histopathological analysis was used as the reference standard. The rate of PI-RADS 3 scores tended to be higher in the presence of radiologically severe prostatitis compared with no/discrete prostatitis ( n = 52 vs. n = 9; p = 0.225). In severe prostatitis, csPCa was determined in only 7.7% (4/52) of PI-RADS 3 lesions. In severe chronic prostatitis, a binary prostatitis suffix (e.g., PI-RADS 3 i+ versus i-) within the radiological report may help assess the limitations of mpMRI interpretability because of severe prostatitis and avoid unnecessary biopsies. Mean apparent diffusion coefficient (ADC mean ) was the best marker (cutoff 0.93 × 10 -3 mm 2 /s) to differentiate between csPCa/non csPCa in severe prostatitis.

Pruritus is one of the disturbing complications induced by chronic liver disease (CLD), bearing a negative impact on patient quality of life and potentially resulting in early liver transplants. Given the main role of the autotaxin enzyme in pruritus induced by CLD and the suppressive effects of melatonin on the expression of the autotaxin gene, this study was designed to evaluate the antipruritic effect of melatonin in patients with CLD. A double-blind, cross-over, randomized, placebo-controlled pilot trial was conducted on patients with CLD -induced pruritis. Patients were randomly assigned to two groups where they received melatonin 10-mg at night or placebo for 2 weeks. After a 2-week washout period, patients were then crossed over to the other group. The Visual Analog Scale (VAS) and the 12-Item Pruritus Severity Score (12-PSS) were used to assess patient response to therapy as the co-primary outcomes, while liver function tests were assayed too. Forty patients completed the study. The VAS score showed alleviation of 3.21 ± 2.24 (in pruritus) with melatonin ( p -value <0.05). The study goal (a reduction of at least 20% in VAS) was achieved in 33 (82%) of study participants. In patients who received melatonin, the 12-PSS and Body Surface Area (BSA) affected by pruritus decreased on average 46.57% and 51.71%, respectively, with mood, sleep pattern and daily activity levels also demonstrating significant improvement ( p -value < 0.05). Melatonin was found to be effective for managing pruritus in patients with CLD.

Introduction: Effective treatments are urgently needed to tackle the novel coronavirus disease 2019 (COVID-19). This trial aims to evaluate sofosbuvir and daclatasvir versus standard care for outpatients with mild COVID-19 infection., Methods: This was a randomized controlled clinical trial in outpatients with mild COVID-19. Patients were randomized into a treatment arm receiving sofosbuvir/daclatasvir plus hydroxychloroquine or a control arm receiving hydroxychloroquine alone. The primary endpoint of the trial was symptom alleviation after 7 days of follow-up. The secondary endpoint of the trial was hospital admission. Fatigue, dyspnoea and loss of appetite were investigated after 1 month of follow-up. This study is registered with the IRCT.ir under registration number IRCT20200403046926N1., Results: Between 8 April 2020 and 19 May 2020, 55 patients were recruited and allocated to either the sofosbuvir/daclatasvir treatment arm (n = 27) or the control arm (n = 28). Baseline characteristics were similar across treatment arms. There was no significant difference in symptoms at Day 7. One patient was admitted to hospital in the sofosbuvir/daclatasvir arm and four in the control arm, but the difference was not significant. After 1 month of follow-up, two patients reported fatigue in the sofosbuvir/daclatasvir arm and 16 in the control arm; P < 0.001., Conclusions: In this study, sofosbuvir/daclatasvir did not significantly alleviate symptoms after 7 days of treatment compared with control. Although fewer hospitalizations were observed in the sofosbuvir/daclatasvir arm, this was not statistically significant. Sofosbuvir/daclatasvir significantly reduced the number of patients with fatigue and dyspnoea after 1 month. Larger, well-designed trials are warranted., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Sofosbuvir seems to be a revolutionary treatment for Hepatitis C-infected patients with advanced chronic kidney disease (CKD) but existing evidence is not quite adequate. The aim of this study was to evaluate the efficacy and safety of Sofosbuvir-based therapy without Ribavirin for all hepatitis C virus genotypes among patients with advanced CKD. We conducted an updated systematic literature search from the beginning of 2013 up to June 2020. Sustained virologic response (SVR) rate at 12 and/or 24 weeks after the end of treatment, and adverse events in HCV-infected patients with advanced CKD were pooled using random effects models. We included 27 published articles in our meta-analyses, totaling 1,464 HCV-infected patients with advanced CKD. We found a substantial heterogeneity based on the I2 index (P = 0.00, I2 = 56.1%). The pooled SVR rates at 12 and 24 weeks after the end of Sofosbuvir-based treatment were 97% (95% Confidence Interval: 95-99) and 95% (89-99) respectively. The pooled SVR12 rates were 98% (96-100) and 94% (90-97) in patients under 60 and over 60 years old respectively. The pooled incidence of severe adverse events was 0.11 (0.04-0.19). The pooled SVR12 rate after completion of the half dose regimen was as high as the full dose treatment but it was associated with less adverse events (0.06 versus 0.14). The pooled SVR12 rate was 98% (91-100) in cirrhotic patients and 100% (98-100) in non-cirrhotic patients. The endorsement of Sofosbuvir-based regimen can improve the treatment of hepatitis C virus infection in patients with advanced CKD., Competing Interests: The authors have declared that no competing interests exist.

This corrects the article "Effectiveness of polypill for prevention of cardiovascular disease (PolyPars): protocol of a randomized controlled trial" published on 2020: Volume 23, Issue 08, Pages 548-556. Correction to: Arch Iran Med. 2020;23(8):548-556. doi: 10.34172/aim.2020.58. In the original version of this article, the recruitment period was wrongly reported to last from December 2014 to December 2015 in abstract and methods sections of the article. This is corrected into "from December 2015 to December 2016" in the PDF and HTML versions of the article. Also the "PolyIran" is changed to "PolyPars" in the last paragraph of the discussion section in the PDF and HTML versions of the article., (© 2021 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: The combination of sofosbuvir and daclatasvir has a well-established safety profile and improves clinical outcomes in HCV patients. In silico and in vitro studies suggest that sofosbuvir/daclatasvir may show antiviral activity against SARS-CoV-2., Methods: Three clinical trials comparing sofosbuvir/daclatasvir-based regimens with a comparator in hospitalized COVID-19 patients were combined in a meta-analysis. The primary outcomes measured were clinical recovery within 14 days of randomization, time to clinical recovery and all-cause mortality. A two-step approach was used to analyse individual-level patient data. The individual trial statistics were pooled using the random-effects inverse-variance model., Results: Our search identified eight studies of which three met the inclusion criteria (n = 176 patients); two studies were randomized and one was non-randomized. Baseline characteristics were similar across treatment arms. Clinical recovery within 14 days of randomization was higher in the sofosbuvir/daclatasvir arms compared with control arms [risk ratio = 1.34 (95% CI = 1.05-1.71), P = 0.020]. Sofosbuvir/daclatasvir improves time to clinical recovery [HR = 2.04 (95% CI = 1.25-3.32), P = 0.004]. The pooled risk of all-cause mortality was significantly lower in the sofosbuvir/daclatasvir arms compared with control arms [risk ratio = 0.31 (95% CI = 0.12-0.78), P = 0.013]., Conclusions: Available evidence suggests that sofosbuvir/daclatasvir improves survival and clinical recovery in patients with moderate to severe COVID-19. However, the sample size for analysis was relatively small, one of the trials was not randomized and the designs were not standardized. These results need to be confirmed in larger randomized controlled trials., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Anterior cervical decompression surgery exposes the vertebral artery to the risk of injury. This risk can increase if the natural course of the vertebral artery is altered. Therefore, this study evaluated if the distance between surgical landmarks and the vertebral artery decrease with the progression of cervical disc degeneration., Methods: This study analyzed 40 patients with cervical magnetic resonance imaging. We evaluated the distance between the uncinate process and the vertebral artery in axial-plane T2 weighted sequences of the cervical levels C3-C6. The cervical disc degeneration was graded according to the Pfirrmann- and Suzuki classification. The decrease of the distance was evaluated using a one-way ANOVA., Results: The distance between the uncinate process and the vertebral artery decreased with increasing disc degeneration (p ≤ 0.015). ROC analysis provided an acceptable area under the curve in both classifications for the detection of a vertebral artery to the uncinate process distance of zero. The presence of Pfirrmann grade V had a positive predictive value of 69% for the presence of contact between the uncinate process and the vertebral artery., Conclusion: High-grade cervical disc degeneration according to the Pfirrmann- and the Suzuki classification decrease the distance between the uncinate process and the vertebral artery. High-grade disc degeneration therefore should raise the awareness of the surgeon for the loss of the distance between surgical landmarks and the vertebral artery. However, screening for high-grade disc degeneration alone cannot substitute the thorough evaluation of the anatomical course of the vertebral artery before surgery., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the most common markers of liver damage, but serum level interpretation can be complicated. In hepatocytes, microRNA-122 (miR-122) is the most abundant miRs and its high expression in the serum is a characteristic of liver disease., Objective: We aimed to compare the circulatory level of miR-122 in patients with Chronic Hepatitis C (CHC), Hepatitis C Virus (HCV) infected Liver Transplant Candidates (LTC) and healthy controls to determine if miR-122 can be considered as an indicator of chronic and advanced stage of liver disease., Methods: MiR-122 serum level was measured in 170 Interferon-naïve (IFN-naïve) CHC patients, 62 LTC patients, and 132 healthy individuals via TaqMan real-time PCR. Serum levels of miR-122 were normalized to the serum level of Let-7a and miR-221. Also, the ALT and AST levels were measured., Results: ALT and AST activities and the expression of circulatory miR-122 were similar in the CHC and LTC groups, but it had significantly increased compared to healthy individuals (P<0.001 and P<0.001, respectively). Up-regulation of miR-122 in the sample of patients with normal ALT and AST activities was also observed, indicating that miR-122 is a good marker with high sensitivity and specificity for diagnosing liver damage., Conclusion: miR-122 seemed to be more specific for liver diseases in comparison with the routine ALT and AST liver enzymes. Since the lower levels of circulating miR-122 were observed in the LTC group compared to the CHC group, advanced liver damages might reduce the release of miR-122 from the hepatocytes, as a sign of liver function deficiency., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Mutations in the core CVR region of hepatitis C virus (HCV) and polymorphisms of interleukin 28B (IL28B) are associated with progression toward liver disease and in response to therapy. In addition, interactions of the core protein with some cell interactors can be related to HCV liver damage., Aim: This study aimed to evaluate the effect of core mutations as well as IL28B polymorphism on clinical features, sustained virological response (SVR) in 1a and 3a HCV genotypes amongst Iranian HCV infected patients, and the impact of mutations on core protein properties, antigenic properties, and interactions with HCV inhibitors, using several bioinformatics tools., Methods: Seventy-nine Iranian patients infected with HCV genotypes 1a and 3a and diagnosed with chronic active hepatitis were examined. Plasma viral RNA was used to amplify and sequence the HCV Core gene; also, HCV viral load, molecular genotyping, and the liver enzymes were determined for all samples. The sequencing results were analyzed by several reliable bioinformatics tools to determine the physicochemical properties, B cell epitopes, post-modification changes, and secondary/tertiary structures; and evaluate the interactions with 4 drugs by docking method., Result: There were some substitutions in core CVR related to ALT and AST enzymes that can lead to HCV advanced liver disease. The most prevalent mutation for 3a genotypes was a substitution in aa 162 (I to V) while we did not find any mutation in 1a responder group. Polymorphism of the rs8099917 showed that the majority of patients had TG heterozygous and carried CT genotype at the rs12979860. Analysis indicated several phosphorylation sits for core protein as well as two important disulfide bonds. Immunogenic prediction showed that core protein can strongly induce the immune system. Interaction analysis, using the docking method revealed two potential interactors (Vitronectin and SETD2)., Conclusion: Generally, mutations in all core CVR regions in all patients showed a relationship between such substitutions and higher liver enzymes that can result in advanced liver disease progression in HCV infected patients. Furthermore, immunoinformatics analysis determined the possible immunodominant regions to be considered in HCV vaccine designs. Furthermore, no association between SVR and IL28B polymorphism was shown. In silico analysis determined modification sites, structures, B-cell epitopes of core protein and interactions with several interactors can lead to persistent HCV infection in the cell and the progress of liver diseases.