Search

Along with all cancer treatments, including chemotherapy, radiotherapy, and surgery, targeting therapy is a new treatment manner. Immunotoxins are new recombinant structures that kill cancer cells by targeting specific antigens. Immunotoxins are composed of two parts: toxin moiety, which disrupts protein synthesis process, and antigen binding moiety that bind to antigens on the surface of cancer cells. Glypican 3 (GPC3) is an oncofetal antigen on the surface of Hepatocellular carcinoma (HCC) cells. In this study, truncated Diphtheria toxin (DT389) was fused to humanized scFv YP7 by one, two and three repeats of GGGGS linkers (DT389-(GGGGS)

Background: High-risk behaviors in people with severe mental illnesses, such drug injection by shared equipment and unprotected sex, expose them to the risk of blood-borne infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Objectives: This study aimed to determine the prevalence of HBV and HCV serum markers in people with severe mental illnesses in Tehran, Iran. Methods: In this cross-sectional study, people with mental illnesses, such as schizophrenia, bipolar disorder, and depression, were studied. The participants were recruited using a non-random convenience sampling method from Roozbeh and Razi hospitals in Tehran between December 2019 and March 2020. Blood samples were evaluated for HCV-Ab, HBs Ag, HBs Ab, and HBc Ab using an enzyme immunoassay technique. Results: A total of 257 participants were recruited for this study; their mean age was 35.77 years, and 70.0% of whom were male. Bipolar disorder (40.5%) and schizophrenia (35.8%) were the most frequent severe mental disorders in the participants. The prevalence of HBV and HCV seromarkers was as follows: HBs Ag: 0.3% (95% CI: 0.0 - 2.0%), HBc Ab: 7.3% (95% CI: 4.6 - 11.3%), HBs Ab: 18.7% (95% CI: 14.1 - 24.0%), and HCV Ab: 3.1% (95% CI: 1.3 - 6.9%). In logistic regression analysis, tattooing (OR = 4.94, 95% CI: 1.73 - 14.13) and age (OR= 1.06, 95% CI: 1.01 - 1.11) were associated with HBV infection (HBc Ab positivity), and only tattooing (OR= 6.33, 95% CI: 1.19 - 33.80) was significantly associated with exposure to HCV. Conclusions: The results of this study showed that the prevalence of HBsAg positivity in people with severe mental illness was not higher than that in the general population of Iran; however, HCV Ab positivity was more prevalent in people with severe mental illness than in the general population of Iran. Preventive, diagnostic, and therapeutic interventions for HCV infection are needed in this population in Iran.

Globally, Non-alcoholic fatty liver disease (NAFLD) has a rising prevalence with no definitive pharmacological treatments. The aim of this study was to assess the clinical effects of wheat germ in patients with NAFLD. Fifty participants with NAFLD were randomly allocated to take 40 g wheat germ (n = 25) or placebo (n = 25) in a randomized double-blind clinical trial over 12 weeks. Transient elastography (FibroScan) determined a diagnosis of NAFLD. After 12 weeks of intervention, reduction in serum alanine aminotransferase (p = 0.006) and γ-glutamyltransferase (p = 0.004), total cholesterol (p = 0.018), triglyceride (p = 0.046), and hepatic steatosis (p = 0.043) levels in the wheat germ group was significantly higher compared to the placebo group. Serum TAC levels in wheat germ group patients increased significantly higher than placebo group (p = 0.001). Reduction in serum hs-CRP level in the wheat germ group was significantly higher than in the placebo group (p = 0.031). In conclusion, our study shows that wheat germ consumption may improve total antioxidant capacity, hepatic steatosis, serum total cholesterol and triglyceride levels, alanine aminotransferase (ALT), and Gamma-glutamyl Transferase (GGT) in NAFLD patients. Longitudinal studies with larger sample sizes are needed to confirm biological effects of wheat germ on NAFLD patients.

IntroductionLow-cost generic direct-acting antiviral (DAA) regimens for treatment of hepatitis C virus (HCV) are available in several low-income/middle-income countries, important for treatment scale-up. This study evaluated the cost-effectiveness of genotype-dependent and pan-genotypic DAA regimens in Iran as an example of a resource-limited setting.MethodsA Markov model was developed to simulate HCV natural history. A decision tree was developed for HCV treatment, assuming four scenarios, including scenario 1: genotyping, sofosbuvir/ledipasvir (SOF/LDV) for genotype 1, and sofosbuvir/daclatasvir (SOF/DCV) for genotype 3; scenario 2: genotyping, SOF/LDV for genotype 1, and sofosbuvir/velpatasvir (SOF/VEL) for genotype 3; scenario 3: no genotyping and SOF/DCV for all; and scenario 4: no genotyping and SOF/VEL for all. A 1-year cycle length was used to calculate the cumulative cost and effectiveness over a lifetime time horizon. We calculated quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) using a health system perspective. Costs were converted to US dollars using purchasing power parity exchange rate ($PPP). All costs and outcomes were discounted at an annual rate of 3%.ResultsAmong people with no cirrhosis, scenario 3 had the minimum cost, compared with which scenario 4 was cost-effective with an ICER of 4583 $PPP per QALY (willingness-to-pay threshold: 9,311 $PPP per QALY). Among both people with compensated or decompensated cirrhosis, scenario 4 was cost saving. In sensitivity analysis, scenario 4 would be also cost-saving among people with no cirrhosis provided a 39% reduction in the cost of 12 weeks SOF/VEL.ConclusionInitiating all patients on pan-genotypic generic DAA regimens with no pretreatment genotyping was cost-effective compared with scenarios requiring pretreatment HCV genotype tests. Among generic pan-genotypic DAA regimens, SOF/VEL was cost-effective, for people with no cirrhosis and cost-saving for those with cirrhosis.

Context: The prevalence of non-alcoholic fatty liver disease (NAFLD) is about 30% in general population. Since conditions such as obesity, hyperlipidemia, diabetes mellitus, metabolic syndrome and insulin resistance have been named as some of the most important risk factors, as the prevalence of these conditions continues to rise, NAFLD becomes an increasingly significant problem. Endothelial dysfunction, increased pulse wave velocity, increased coronary artery calcification, and the development of atherosclerosis appear to be influenced by NAFLD. Considering this concern, this narrative review investigated the prevalence of CVD in NAFLD patients. Evidence Acquisition: This narrative study evaluates the prevalence of CVD in NAFLD patients, as well as several variables that influence their association. In this study our search strategy engines include PubMed, Scopus, MEDLINE, and Google Scholar. Results: Previous research suggests that as nonalcoholic steatohepatitis (NASH) and liver fibrosis progress, there is an increased risk of CVD, most likely due to the hepato-cardiovascular axis' effect. The correlation between NAFLD and metabolic disorders suggests that fatty liver disease may cause cardiovascular disorders (CVD). Conclusions: As a result, the management of both NAFLD and the risk of CVD are aimed at the same target, which is to reduce insulin tolerance by lifestyle modifications. Moreover, monitoring for CVD and proper pharmacotherapy is essential in individuals with severe NAFLD and those who are at increased risk for ischemic heart disease.

New technologies are supported by the global implementation of the internet. These improvements have deeply affected various disciplines of sciences and consequently changed services such as daily business, particularly health sectors. Innovative digital marketing strategies utilize the channels of social media and retrieved user data to analyze and improve relevant services. These multidisciplinary innovations can assist specialists, physicians and researchers in diagnostic, prophylaxis and treatment issues in the health sector. Accordingly, compared to recent decades, health decision makers are more accurate and trustful in defining new strategies. Interestingly, using social media and mobile health apps in current pandemics of SARS-CoV-2 could be an important instance of the key role of these platforms at the local and global level of health policies. These digital technologies provide platforms to connect public health sectors and health politicians for communicating and spreading relevant information. Adding influencers and campaigns to this toolbox strengthens the implementation of public health programs. In 2016, the WHO adopted a global program to eliminate viral hepatitis by 2030. Recent constructive measures that have been used in the battle against COVID-19 could be adopted for the elimination of viral hepatitis program. The presented evidence in our narrative review demonstrates that the application of digital marketing tools to create campaigns on social media, armed with professional influencers, can efficiently consolidate this program. The application of different strategies in using these popular tools will raise the public awareness about viral hepatitis. Subsequently, the availability of an effective vaccine for HBV and antiviral medication for HCV can motivate the audience to take steps towards prophylaxis and screening methods against these infectious illnesses. The encouragement of health policy makers to apply digital communication technologies and comprehensive roadmaps to implement this global program will certainly decrease the burden of viral hepatitis worldwide. ispartof: PATHOGENS vol:11 issue:6 ispartof: location:Switzerland status: published

IntroductionNon-alcoholic fatty liver disease (NAFLD) is a hepatic condition that is considerably prevalent across the world. Dietary intakes, in which macronutrient composition is precisely planned, might be able to reduce inflammation, steatosis and fibrosis among patients with NAFLD. A moderately carbohydrate restricted diet with weight loss has been demonstrated to improve liver fat content among overweight or obese patients. However, there is no information about the appropriateness of such a restriction, without weight loss, in normal-weight patients. This randomised clinical trial will be aimed at assessing the effect of moderate carbohydrate restriction on liver enzymes, liver steatosis and fibrosis in normal-weight patients with NAFLD.Methods and analysisThis randomised controlled clinical trial will be conducted to evaluate the impact of a moderately carbohydrate restricted diet on liver enzymes, steatosis and fibrosis in 52 eligible normal-weight individuals with NAFLD. Transient elastography and controlled attenuation parameter with FibroScan will be applied to diagnose NAFLD. After individual matching based on body mass index, age and sex, patients will be randomly assigned to receive a moderately carbohydrate restricted diet or an isocaloric diet without carbohydrate restriction for 12 weeks. The primary and secondary outcomes in this study will be liver function indices, including liver steatosis and fibrosis, metabolic parameters and anthropometric measures. All these variables will be assessed at study baseline and postintervention.Ethics and disseminationThe present clinical trial study was accepted by the ethics committee of TUMS (Tehran University of Medical Sciences) (code: IR.TUMS.MEDICINE.REC.1400.116).Trial registration numberIRCT20210119050086N1.

This study was conducted to present the mechanism of the therapeutic effects of Chlorella vulgaris extract (CV) on the carbon tetrachloride (CCl4) induced liver fibrosis model. Primarily, the mechanism of antioxidant effects of CV were investigated via measuring the expression of forkhead box protein O1 (FOXO1) and phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK) as upstream regulators of superoxide dismutase (SOD) and catalase (CAT). Subsequently, we investigated the regulatory effect of CV treatment on the yes-associated protein (YAP) and transcriptional coactivators with a PDZ-binding motif (TAZ) as fibrogenic factors. Male Wistar rats received CCl4 and olive oil solution 1 ml/kg intraperitoneally for 12 weeks, twice weekly. CV 50 and 100 mg/kg were administered on a daily basis by gavage in the last 4 weeks. Ultimately, liver marker enzymes and hepatic hydroxyproline content were measured. The activity of SOD and CAT and the expression of YAP, TAZ, FOXO1, SOD, and CAT were analyzed. Finally, the protein levels of YAP, TAZ, and p-AMPK were detected. CV administration decreased liver marker enzymes and hydroxyproline content significantly. The expression and protein levels of YAP and TAZ reduced by CV treatment. Furthermore, the augmentation of expression and function of CAT and SOD by CV treatment was followed by an increase in the expression of FOXO1 and protein level of p-AMPK. Our data revealed that the stimulation of expression and function of SOD and CAT by CV treatment could be mediated by FOXO1/p-AMPK axis. Moreover, anti-fibrotic effect of CV might be associated with its inhibitory effect on the hepatic expression of YAP and TAZ. Chlorella vulgaris treatment ameliorates liver fibrosis via two cellular mechanisms. A) Likely, Chlorella vulgaris treatment increases gene expression of enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) via upregulating its upstream regulatory elements i.e. phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK) and forkhead box protein O1 (FOXO1). These possible regulatory effects maybe lead to reduce reactive oxygen species level (ROS). B) Chlorella vulgaris treatment decreases hepatic protein level and gene expression of key elements of Hippo signaling pathway i.e. Yes-associated protein (YAP) and Transcriptional coactivators with a PDZ-binding motif (TAZ). Figure created with BioRender ( https://biorender.com ). ROS: Reactive oxygen species, YAP: Yes-associated protein, TAZ: Transcriptional coactivators with a PDZ-binding motif, FOXO1: Fork head Box O1, AMPK: 5′ adenosine monophosphate activated protein kinase, SOD: Superoxide dismutase, CAT: Catalase, P: Phosphate group.

Coinfections of hepatitis C virus (HCV) and/or hepatitis B virus (HBV) with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) are associated with high morbidity and mortality and poor prognosis. The main objective of this study was to evaluate the prevalence of HCV and/or HBV coinfections among people who inject drugs (PWID) and female sex workers (FSWs) who live with HIV/AIDS worldwide. Data sources were searched from January 2008 to October 2018 in different databases, including PubMed, Scopus, Web of Science, Embase, and Ovid. Data were analyzed in Stata 14 software using the Metaprop command. The results showed that the prevalence of HCV among PWID and FSWs with HIV/AIDS was 72% (95% CI: 59%-83%) and 40% (95% CI: 0%-94%), respectively. The prevalence of HBV among PWID and FSWs with HIV/AIDS was 8% (95% CI: 5%-13%) and 2% (95% CI: 0%-7%), respectively, and the prevalence of HCV/HBV in PWID with HIV/AIDS was 11% (95% CI: 7%-15%). The highest prevalence of HCV was observed in PWID in the Eastern Mediterranean and Europe regions, and the lowest was observed in the Africa region. The South-East Asia region had the highest prevalence of HBV among PWID, and the Africa region had the lowest prevalence. The high prevalence of HCV coinfection among PWID and FSWs with HIV/AIDS was an alarming health problem and requires appropriate interventions. Therefore, considering that these populations are key populations for HCV elimination, it is recommended to screen them regularly for HCV. In addition, harm reduction and HBV vaccination should be carefully considered.

Patients undergoing regular hemodialysis (HD) are at an extreme risk of acquiring bloodstream infections compared to the general population. Hepatitis E virus (HEV) infection is an important emerging health issue in these patients. To date, numerous studies have investigated the seroprevalence of HEV among HD patients across the world; however, the data are conflicting. The present study aimed to measure the exposure rate of HD patients to HEV infection by estimating the overall seroprevalence of HEV in this high-risk group. A systematic literature search was carried out using five electronic databases from inception to January 10, 2020, with standard keywords. Pooled seroprevalence estimates with 95% confidence intervals (CIs) were calculated using a random intercept logistic regression model. The seroprevalence of HEV increased from 6.6% between the years of 1994 and 2000 to 11.13% from 2016 to 2020. Blood transfusion was associated with a nearly 2-fold increase in the rate of HEV seropositivity (OR = 1.99; 95% CI: 1.50-2.63, P < .0001, I2 = 6.5%). HEV seroprevalence among patients with HD for more than 60 months was significantly higher than those with HD for less than 60 months (27.69%, 95% CI: 20.69%-35.99% vs 15.78%, 95%CI: 8.85%-26.57%, respectively) (P = .06). Our results indicated increased exposure of HD patients with HEV infection over the last decade. We concluded that blood transfusion and duration of HD are considerable risk factors for acquiring HEV infection among HD patients.

Studies have reported that the immune system modulation genes are involved in the seroconversion during hepatitis B virus (HBV) infection. Here, a systematic review with meta-analysis is implemented on the association of polymorphisms in immune-related genes with the spontaneous hepatitis B surface antigen (HBsAg) seroconversion.A systematic literature search was conducted in the main electronic databases of Scopus, PubMed, and Web of Science before May 2022. Pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were used to evaluate the strength of the association between genetic polymorphisms and the chance of spontaneous HBsAg seroconversion.A total of 40 studies finally included for meta-analysis of 2 HLA-DP SNPs, 2 HLA-DQ SNPs, 3 IFNL3/4 SNPs, 2 IL10 SNPs, and 5 TNF SNPs. Based on the overall pooled analysis, HLA-DP rs3077 A (OR = 1.47, 95%CI: 1.32-1.65), HLA-DP rs9277535 A (OR = 1.48, 95%CI: 1.32-1.66), HLA-DQ rs2856718 G (OR = 1.37, 95%CI: 1.18-1.59), HLA-DQ rs7453920 A (OR = 1.41, 95%CI: 1.04-1.93), IFNL3/4 rs12980275 G (OR = 1.26, 95%CI: 1.01-1.58), TNFA rs1799964 T (OR = 1.17, 95%CI: 1.02-1.35), and TNFA rs1800630 C (OR = 1.26, 95%CI: 1.03-1.55) increased significantly the chance of spontaneous HBsAg seroconversion.This meta-analysis showed that the HLA-DP gene rs3077 and rs9277535 SNPs, HLA-DQ gene rs2856718 and rs7453920 SNPs, IFNL3/4 gene rs12980275 SNP, TNFA gene rs1799964 and rs1800630 SNPs are involved in the spontaneous HBsAg seroconversion.

Background: Several studies have revealed that the hepatitis B virus (HBV) exists in peripheral blood mononuclear cells (PBMCs). It remains poorly understood whether HBV DNA and covalently closed circular DNA (cccDNA) can emerge in PBMCs of patients with different stages of HBV infection. Objectives: This study aimed to compare the detection of HBV DNA and quantification and presence of cccDNA within PBMC from patients with chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC). Methods: The present study was conducted on 120 participants (30 CHB patients, 30 cirrhosis patients, 30 HCC patients, and 30 healthy controls) from Tehran, Iran. HBV serological markers were tested by enzyme-linked immunosorbent assay (ELISA). PBMCs of all individuals were assayed for HBV DNA detection, quantification, and the presence of cccDNA. Results: Of 90 HBV patients, 58 (64.4%) were positive for HBV DNA in PBMCs. HBV DNA was detected in PBMCs isolated from 13/30 CHB, 20/30 cirrhosis, and 25/30 HCC patients. In addition, 6 (20%) CHB, 13 (43.3%) cirrhosis, and 16 (15.3%) HCC patients were cccDNA positive. The HBV viral loads in serums were statistically higher than the HBV viral loads of PBMCs (P < 0.001). A positive correlation was found between HBV DNA loads in serums and PBMCs of patients. Moreover, HBV DNA quantity of serums and PBMCs showed a significant association in terms of hepatitis B e antigen (HBeAg) status. Conclusions: HBV quantity in PBMCs correlated with serum HBV viral loads. HBV genomes in PBMCs may be a risk factor for HBV disease progression.

Hesperidin as an antioxidant flavonoid exerts anti-adipogenic, anti-inflammatory, anti-oxidant and anti-hypercholesterolemic effects. Besides, the increasing prevalence of metabolic syndrome (MetS) and its allied complications, on the one hand, and the willingness of individuals to use natural products for curing their diseases, on the other hand, led to the design of this study to evaluate the efficacy of hesperidin in normalizing the metabolic abnormalities in patients with MetS. In this clinical trial with a parallel-group design, 49 patients with MetS received either 500-mg hesperidin or placebo, twice daily, for 12 weeks. Number of participants with treated MetS was considered as a primary end point. Anthropometric parameters, dietary intake, physical activity, lipid profile, glucose homeostasis parameter, tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP) were assessed at the beginning and at the end of the study. This trial is registered at clinicaltrials.gov as NCT03734874. Compared with the placebo group, hesperidin decreased fasting glucose level (− 6.07 vs. − 13.32 mg/dL, P = 0.043), triglyceride (− 8.83 vs. − 49.09 mg/dL, P = 0.049), systolic blood pressure (− 0.58 vs. − 2.68 mmHg, P = 0.048) and TNF-α (− 1.29 vs. − 4.44 pg/mL, P = 0.009). Based on the within-group analysis, hesperidin led to significant decrease in serum levels of glucose, insulin, triglyceride, total cholesterol, low density lipoprotein cholesterol, TNF-α and hs-CRP, while in control group only glucose and insulin significantly decreased. The results indicate that hesperidin supplementation can improve metabolic abnormalities and inflammatory status in patients with MetS.

Background: Hepatitis C virus (HCV) can lead to increased mortality, disability, and liver transplantation if left untreated, and it is associated with a possible increase in disease burden in the future, all of which would surely have a significant impact on the health system. New antiviral regimens are effective in the treatment of the disease yet expensive. Objectives: The purpose of the present study was to assess the cost-effectiveness of three medication regimens, namely, ledipasvir/sofosbuvir (LDV/SOF), velpatasvir/sofosbuvir, and daclatasvir/sofosbuvir (DCV/SOF) for HCV patients with genotype 1 in Iran. Methods: A Markov model with a lifetime horizon was developed to predict the costs and outcomes of the three mentioned medication therapy strategies. The final outcome of the study was quality-adjusted life-years (QALYs), which was obtained using the previously published studies. The study was conducted from the perspective of the Health Ministry; therefore, only direct medical costs were estimated. The results were provided as the incremental cost-effectiveness ratio (ICER) per QALY. Ultimately, the one-way and probabilistic sensitivity analyses were used to measure the strength of study results. Results: The results showed that the QALYs for LDV/SOF, DCV/SOF, and VEL/SOF were 13.25, 13.94, and 14.61, and the costs were 4,807, 7,716, and 4,546$, respectively. The VEL/SOF regimen had lower costs and higher effectiveness than the LDV/SOF and DCV/SOF regimens, making it a dominant strategy. The tornado diagram results showed that the study results had the highest sensitivity to chronic hepatitis C (CHC) and compensated cirrhosis (CC) state costs. Moreover, the scatter plots showed that the VEL/SOF was the dominant therapeutic strategy in 73% of the simulations compared to LDV/SOF and 66% of the simulations compared to DCV/SOF; moreover, it was in the acceptable region in 92% of the simulations and below the threshold. Therefore, it was considered the most cost-effective strategy. Moreover, the results showed that DCV/SOF was in the acceptable region below the threshold in 69% of the simulations compared to LDV/SOF. Therefore, the DCV/SOF regimen was more cost-effective than LDV/SOF. Conclusions: According to the present study results, it is suggested that the VEL/SOF regimen be used as the first line of therapy in patients with HCV genotype 1. Moreover, DCV/SOF can be the second-line medication regimen.

People who inject drugs (PWID) are at high risk for hepatitis C virus (HCV) infection and its complications in many countries, including Iran. This pilot study aimed to evaluate the effect of a community-based HCV model of care on HCV testing and treatment initiation among PWID in Kerman, Iran.This study is part of the Rostam study and is a non-randomized trial evaluating the effect of on-site HCV- antibody rapid testing, venipuncture for HCV RNA testing, and treatment eligibility assessment on HCV testing and treatment initiation among PWID. Recruitment, interviews, and HCV screening, diagnosis, and treatment were all conducted at a community-based drop-in center (DIC) serving PWID clients.A total of 171 PWID (median age of 39 years and 89.5% male) were recruited between July 2018 and May 2019. Of 62 individuals who were HCV antibody positive, 47 (75.8%) were HCV RNA positive. Of RNA-positive individuals, 36 (76.6%) returned for treatment eligibility assessment. Of all the 36 participants eligible for treatment, 34 (94.4%) initiated HCV antiviral therapy. A sustained virologic response at 12 weeks post-treatment was 76.5% (26/34) in the intention-to-treat (ITT group) analysis and 100% (23/23) in the per-protocol (PP group) analysis.Our integrated on-site community-based HCV care model within a DIC setting suggested that HCV care including HCV testing and treatment uptake can be successfully delivered outside of hospitals or specialized clinics; a model which is more likely to reach PWID and can provide significant progress towards HCV elimination among this population.

Background: Unawareness and inappropriate attitude toward hepatitis B can expose healthy people, especially immigrants, to a higher risk of hepatitis B transmission. The present study aimed to determine the effect of hepatitis B prevention education by face-to-face and distance training on the knowledge and attitude of Afghan immigrant students. Methods: This randomized controlled trial was conducted on 128 voluntary immigrant nonmedical Afghan students of Imam Khomeini University in Qazvin City, Iran. The study subjects were randomly assigned to 4 groups (A1, A2, B1, & B2), and the training was performed using Solomon’s four-group-design. The A groups received face-to-face education, while the B groups received distance education through email and Telegram messenger. The required data were collected using a self-structured questionnaire at three-time intervals of before, immediately after, and one month after training. The collected data were analyzed by the Chi-squared test, Independent Samples t-test, Paired Samples t-test, and repeated-measures Analysis of Variance (ANOVA) using SPSS. Results: Based on the study findings, the improvement of knowledge and attitude values was more significant in the face-to-face groups, compared to the distance education groups. However, there was a significant difference in both methods (P

Background Stimulants substances use, particularly methamphetamine use, is increasing globally, including in Iran. This study assessed the drug use and risk behaviour profile, and prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among a large population using methamphetamine as their primary drug in Iran. Methods This cross-sectional study was conducted in eight provinces of Iran. Individuals using methamphetamine for ≥3 months during the past three years, with no life-time history of injecting opioid drugs were enrolled. Drug use and risk behaviour data were collected through interviews. Blood samples were tested for HIV antibodies (HIV Ab), HCV antibodies (HCV Ab), and HBV surface antigen (HBs Ag). Result Among 567 participated, 84% were men and mean age was 36 years. Smoking with pipe was the most common method of methamphetamine use (53%), while 13% had a history of injecting methamphetamine, among whom 30% shared needles or syringes. Among those having sex during intoxication phase (n = 270), 48% never used condom. The prevalence of HIV Ab, HCV Ab and HBs Ag was 6.7% (95%CI: 4.7–9.1), 19.4% (95%CI: 16.2–22.9) and 1.4% (95%CI: 0.6–2.7), respectively. Age ≥ 30 years (adjusted OR [aOR]: 2.10, 95%CI: 1.18–3.76), lower education (high school vs. tertiary education, aOR: 13.95, 95%CI: 1.90–102.60), and injecting methamphetamine (aOR: 1.92, 95%CI 1.10–3.35) were significantly associated with HCV exposure. No factor was found associated with HIV infection. Among those reporting no potential injecting or sexual risk factors, 19.8% and 6.8% have HCV Ab positive and HIV Ab positive, respectively. Conclusion High prevalence of injecting and sexual risk behaviours, HIV infection and HCV exposure were found among individuals using methamphetamine as their primary drug, demonstrating them as an emerging population at risk of HIV and HCV in Iran. Targeted screening and harm reduction programs for this population are required.

BACKGROUND AND AIM Cirrhosis is a major public health problem worldwide. The prevalence of cirrhosis is various in different geographical regions. The aim of the present study was to determine the distribution of the etiologies of cirrhosis and their proportional changes through recent 11 years in Iran. METHODS In this retrospective, observational study, the data of cirrhotic patients who have been listed for liver transplantation in the Namazi Transplant Center (Shiraz, Iran) between January 2006 and December 2016 were analyzed. Demographic and clinical data of the patients including model for end-stage liver disease score, year of registration, and the etiologic diagnosis for each patient were retrieved. RESULTS The ratio of males to females was the highest (2.6:1) in patients with age over 50 years. Of 4891 patients, hepatitis B virus cirrhosis had the highest frequency (23.53%) and alcoholic cirrhosis had the lowest frequency (1.70%). The percentages of waiting list patients with hepatitis B virus (34.48%-17.48%) (P < 0.001), autoimmune hepatitis (12.64%-8.50%) (P = 0.037), and alcoholic cirrhosis (2.30%-1.10%) were decreased (P = 0.008) and the percentages of waiting list patients with cholestatic (12.64%-25.20%) and nonalcoholic steatohepatitis cirrhosis (0.77%-8.82%) were increased over 11 years (both P < 0.001). Hepatitis B virus and autoimmune hepatitis cirrhosis were the most prevalent in male and female patients, respectively. CONCLUSION The results of the present study showed an increase in the frequency of cholestasis and nonalcoholic steatohepatitis cirrhosis and therefore it should be considered in the health policy implementation.

Using direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection results in a high treatment response rate. However, several factors can significantly alter this outcome such as resistance-associated substitutions (RASs) in HCV NS5A gene. This study aimed to evaluate the prevalence of naturally occurring RASs of NS5A in HCV genotype 3 (HCV-3) sequences isolated from individuals with chronic HCV-3 infection. All the registered sequences in the GenBank under "NS5A" AND "Hepacivirus C" query were evaluated and screened, those which followed our inclusion criteria were enrolled in our pooled analysis. The retrieved sequences of included studies were evaluated for substitutions, RASs, and RASs conferring100 resistance fold change (RASs100 × ) in NS5A amino acid positions 24, 28, 30, 31, 62, 92, and 93. From 7 enrolled studies, a total of 370 HCV-3a isolates were retrieved and investigated. Forty-eight (13.0%, 95% CI = 9.9-16.8%) isolates harbored NS5A RASs. Moreover, Y93H was the only NS5A RAS100 × observed in 13 (3.5%, 95% CI = 2.0-5.9%) retrieved sequences. The low frequency of naturally occurring NS5A RASs, especially those with clinical relevance (RASs100 × ), among individuals with HCV-3 infection and the high rate of treatment response to DAAs suggest not to investigate every individual with HCV-3 infection for NS5A RASs before treatment.

Chronic liver disease (CLD) is a major health problem worldwide. Non-alcoholic fatty liver disease (NAFLD), chronic hepatitis C (CHC), chronic hepatitis B (CHB), and alcoholic liver disease (ALD) are the most common etiologies of CLD. Liver biopsy is the gold standard for assessment of liver fibrosis, however, it is an invasive method. This review attempts to evaluate the usefulness of serum adiponectin, serum leptin, serum ferritin, serum transforming growth factor-β1 (TGF-β1), and serum platelet derived growth factor-BB (PDGF-BB) as non-invasive markers in the diagnosis of liver fibrosis/cirrhosis. A systematic search in MEDLINE, Web of Science, Scopus, and local databases was performed to identify articles published in English or Persian as of November 2017. Studies conducted among CLD patients, with biopsy proven fibrosis/cirrhosis, and providing sufficient details of patients’ clinicopathological characteristics were included. In the 95 studies included, there were a total of 15,548 CLD patients. More than 83% of studies were carried out in Asia and Europe. The relationship between liver fibrosis/cirrhosis and serum levels of ferritin, adiponectin, leptin, TGF-β1, and PDGF-BB was assessed in 42, 33, 27, nine, and three studies, respectively. Serum levels of the markers, particularly ferritin, could successfully predict liver fibrosis/cirrhosis, however, these data might not be clinically replicated and further studies are needed.

Hepatitis D is considered to be the most severe form of viral hepatitis. This virus requires hepatitis B for its life cycle and it is estimated that at least 5% of hepatitis B virus infected patients are also infected with hepatitis D, counting for 15 million infections worldwide most optimistically. Hepatitis D has a similar transmission pattern to hepatitis B and hepatitis C viruses. However, there is less information about the virus of hepatitis D than about the other agents of viral hepatitis. In particular, there is total lack of information on hepatitis D in the setting of dental diseases and management. To our knowledge, there are only few reports on hepatitis D of dental health care workers (DHCW), the association of hepatitis D with oral conditions and on the role of oral fluid in transmission of hepatitis D. The present report reviews current knowledge of hepatitis D for dentists and dental personnel. Therefore, epidemiology, transmission modes, sign and symptoms, diagnostic methods and treatment options of hepatitis D are discussed under relevant subheadings.

Background: Although several regimens have been approved for the treatment of hepatitis C virus (HCV) infection, sofosbuvir-based regimens are not approved for the treatment of HCV infection in patients with severe renal impairment. Methods: This study was conducted on hemodialysis patients infected with HCV. The patients received a constant dose of sofosbuvir/daclatasvir (SOF/DCV). Sustained virologic response (SVR) was evaluated 12 weeks after completion of treatment. Results: Fifty-one hemodialysis patients with HCV infection were selected and treated with a combination of SOF/DCV. Eleven patients expired during the anti-HCV treatment due to causes not related to liver disease or antiviral therapy. Finally, 40 patients finished the treatment, and 36 cases were evaluated for SVR. Among those tested for SVR, 35 (97.2%, 95% CI: 85.5 - 99.9%) achieved SVR and one (2.8%, 95% CI: 0.1 - 14.5%) relapsed. No patient reported severe adverse events. Conclusions: The combination of SOF/DCV showed great efficacy and safety in hemodialysis patients with severe renal impairment and chronic HCV infection.

Background: Behcet's disease (BD) is a chronic multisystem vasculitis with an unknown etiology. During the past years, several reports are published on the occult hepatitis B infection (OBI), the presence of hepatitis B virus (HBV) DNA in the absence of HBsAg, in rheumatic diseases. Objectives: The current study aimed to, firstly, investigate the prevalence of OBI in patients with BD, and, secondly, its potential association with the clinical and therapeutic status of BD. Methods: HBV serological markers and HBV DNA were evaluated in 220 consecutive BD patients to detect OBI. Demographic and clinical data of OBI positive and negative groups were compared. Results: The mean age of patients was 39.24 (± 10.57), and 134 (62.9%) were male. The mean disease duration was 14.13 (± 8.63) years. No HBsAg positive case was found, but HBV DNA was found in 19 (8.6%) patients. The median viral load value was 475.84 copy/mL. We compared clinical data of 10 OBI positive and 156 OBI negative BD patients with complete and accessible data. There was no difference between the two groups concerning demographic characteristics (age, sex, and disease duration), different clinical manifestations, or types of medications (immunomodulatory, cytotoxic, and corticosteroids). Conclusions: This is the first study showing a rather high prevalence of OBI among BD patients. We did not find any correlation between OBI positivity and different clinical manifestations, medications, or HLA-B51. Further studies are needed on a larger group of patients and by molecular HBV evaluation (as well as serologic) regarding this possible association.

Background: The increased prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) has caused several concerns. Besides, there are concerns about the side effects of the drugs used to treat this condition. Since the current treatments are not effective in treating NAFLD, developing a novel therapeutic option based on some medicinal plants is necessary. Few studies have investigated the natural drugs and their effects (e.g., extracts of Carum Copticum Seeds (CCS)) on these patients. Objectives: The current study intended to evaluate the safety and efficacy of CCS extracts on liver enzymes, serum lipids, as well as the grade of fatty liver, and anthropometric measurements in patients with nonalcoholic fatty liver disease. Methods: In this multi-center, randomized, triple-blind, placebo-controlled clinical trial study, 90 patients with grades of 1 to 3 of nonalcoholic fatty liver disease referred to two medical centers located in Tehran (Iran) in 2019 are examined. Diet and exercise were recommended for patients three times a day in eight weeks, in addition to taking 500 mg capsules (aqueous extracts of Ajwain seeds and placebo for treatment and placebo groups). Results: Medical records of 68 patients were reviewed, 48 (71%) male and 20 (29%) female. Both groups were similar concerning demographic and baseline characteristics. The total score of the Leeds questionnaire [-14.03 vs. -7.49, P = 0.048], Triglyceride (TG) [-4.45 vs. 10.03, P = 0.017], and Alanine Aminotransferase (ALT) [-14.71 vs. -4.79, P = 0.012] were significantly changed in the treatment group compared to the control group. Nevertheless, a different situation was observed for Aspartate Aminotransferase (AST) [-7.08 vs. -4.84, P = 0.314], Fasting Blood Sugar (FBS) [-2.88 vs. -2.81, P = 0.207], and Body Mass Index (BMI) [-0.59 vs. -0.39, P = 0.095]. Although a significant change was found in both groups, the amount of decline was similar for both groups. In both groups, the cholesterol, High-Density Lipoprotein (HDL), and Low-Density Lipoprotein (LDL) did not change significantly. The sonographic findings indicated significantly higher improvements in the intervention group than the placebo group (RR = 2.43, 95% CI (1.15-5.65), and P value = 0.034). Conclusions: The result of this study supports the efficacy of Carum copticum seeds in the treatment of nonalcoholic fatty liver disease patients. It was found that CCS with a significant reduction in ALT, TG, and relative reduction of BMI can help physicians to manage other metabolic disorders associated with NAFLD, such as obesity and hyperlipidemia.

Background Prevalence of hepatitis C virus (HCV) infection among people who inject drugs (PWID) in Iran is high. Since 2005, the Iranian government has implemented a harm reduction program to control HCV. We aimed to describe the prevalence of HCV antibody (Ab) in Iranian PWID before and after the implementation of harm reduction with cumulative meta-analysis. Methods Following PRISMA guidelines, we conducted a systematic review and meta-analysis of studies published on the seroprevalence of HCV among PWID. We systematically reviewed the literature to identify eligible studies up to December 2018 in international and national databases. Pooled prevalence and 95% confidence intervals were calculated using Der Simonian and Laird method, taking into account conceptual heterogeneity. Subgroup analyses were performed by harm reduction implementation and studies’ characteristics to assess the sources of heterogeneity. We used Cochran–Armitage test for the linear trend of the prevalence of HCV Ab among PWID. Results We reviewed 5966 papers and reports and extracted data from 62 eligible records. The pooled HCV Ab prevalence among PWID in Iran was 46.5% (95% confidence interval [95% CI] 41.1–52.0%). Overall, the Cochran–Armitage test for trend indicated a significant decreasing trend of HCV Ab prevalence (P = 0.04). The cumulative meta-analysis showed a slight decline in the prevalence of HCV Ab between the years 2005 and 2018. Conclusions The HCV Ab prevalence among PWID in Iran is high, with a considerable geographical variation. The prevalence of HCV Ab among PWID in Iran slightly decreased after 2005 which could be, at least to some extent, related to the implementation of extensive harm reduction programs in the country.

Context: Hepatocellular carcinoma (HCC), as the most common type of primary liver cancer (accounting for 70% - 90% of all liver cancers), is the seventh most common malignancy worldwide. Glutathione S-transferases (GSTs) are a specific group of enzymes that are responsible for the detoxification of carcinogens. According to the available literature, genetic variations in this group of enzymes may be associated with the risk of HCC. In this study, we aimed to assess the association of GSTM1 and GSTT1 null deletions and GSTP1 rs1695 polymorphism with the risk of HCC. Methods: We systematically searched electronic databases, including PubMed, Scopus, and Web of Science, using appropriate keywords to gather relevant data until March 2019. Studies that met the inclusion criteria were included in the meta-analysis, using either fixed- or random-effects models based on the presence of heterogeneity. Results: This meta-analysis pooled 19 studies for GSTM1 null deletions, 14 studies for GSTT1 null deletions, and five studies for GSTP1 rs1695 polymorphism. In terms of heterogeneity, the pooled odds ratio (OR) was calculated in a random-effects model for both Asian and non-Asian populations. HCC was found to be associated with GSTM1 null deletions (OR = 1.26, 95% CI: 1.00 - 1.58, P = 0.05) and GSTT1 null deletions (OR = 1.39, 95% CI: 1.10 - 1.74, P = 0.005); however, no significant association was found between HCC and GSTP1 rs1695 polymorphism (OR = 1.14, 95% CI: 0.86 - 1.50, P = 0.36). Conclusions: We found that GSTM1 and GSTT1 null deletions increased the risk of HCC; however, the GSTP1 rs1695 polymorphism did not have a similar effect.

BackgroundHepatitis C virus (HCV), non-structural 5A (NS5A), and non-structural 5B (NS5B) resistance-associated substitutions (RASs) are the main causes of failure to direct-acting antiviral agents (DAAs). NS5A and NS5B RASs can occur in patients with HCV infection naturally and before exposure to DAAs.ObjectivesThis study aimed to evaluate naturally-occurring NS5A and NS5B RASs in Iranian patients with HCV genotype 1a (HCV-1a) and -3a infections.MethodsIn this cross-sectional study, viral RNA was extracted from serum specimens. NS5A and NS5B regions were amplified using RT-PCR followed by DNA sequencing. The results of nucleotide sequences were aligned against reference sequences of HCV-1a and -3a and the amino acid substitutions were analyzed using geno2pheno [hcv] web application.ResultsAmong 135 patients with hepatitis C, NS5A amino acid substitutions/RASs were identified in 26.4% and 15.9% of patients with HCV-1a and -3a infections, respectively. The identified amino acid substitutions/RASs in the NS5A region of patients with HCV-1a infection were M28T/V/I 11.1%, Q30R/H 4.2%, L31M 1.4%, and H58Y/P/C/D/Q/S/T 16.7%. Y93H substitution was not found in HCV-1a sequences. In patients with HCV-3a infection, NS5A amino acid substitutions/RASs were A30T/K 9.5%, L31F 1.6%, P58S/T/C 3.2%, Y93H 3.2%, and Y93N 3.2%. No resistance substitutions were identified in NS5B sequences from patients with HCV-1a and -3a infections.ConclusionIn this study, baseline amino acid substitutions/RASs were only identified in the NS5A region in Iranian patients with HCV-1a and -3a infections, and the prevalence of these amino acid substitutions/RASs were in accordance with similar studies. There were no RASs in the HCV-1a and -3a NS5B region.

Background: Eliminating high-risk individuals has a special role in ensuring blood safety. Due to epidemiological, demographic, and even cultural changes in each country, this process should be continuously evaluated and reviewed, if necessary. Objectives: This study aimed to evaluate the impact of the current donor selection procedure on blood safety in Iran. Methods: A total of 2,525 high-risk deferred donors who were referred between 2018 and 2019 were evaluated regarding hepatitis B surface antigen, hepatitis C virus antibody, and human immunodeficiency virus antigen and antibody. All repeatedly reactive samples were evaluated by confirmatory tests. Characteristics' parameters, donor status, and TTI marker rates of the participants and 1,315,871 eligible donors in the indicated period obtained from the national database on blood donors, were compared. Data were analyzed using SPSS version 24.0. Results: The prevalence of HBV, HCV, and HIV in 100,000 deferred donors was 1148, 515, and 119, respectively. This prevalence was 26, 28, and 33-times higher than the eligible donors, respectively. Unlike HBV, its prevalence among males was almost twice that of females among the deferred group. In the eligible group, females had a higher prevalence for HBV and HCV as compared to males. The HCV and HBV (6.7 and 4.3-fold) among deferred first-time donors had a significantly higher prevalence compared with the eligible first-time donors (P‐value < 001). Notably, the higher was the education degree, the lower was the prevalence of infection in both groups. Conclusions: Current deferral criteria and donor selection procedure in Iran are an opportunity to eliminate high-risk individuals from the blood donation.

Background People with criminal justice involvement contribute remarkably to the rising hepatitis C virus (HCV) burden; however, the continuum of care is a major barrier to prison-based programs. We aimed to evaluate a comprehensive HCV care model in an Iranian provincial prison. Methods Between 2017–2018, in the Karaj Central Prison, newly admitted male inmates received HCV antibody testing and venipuncture for RNA testing (antibody-positive only). Participants with positive RNA underwent direct-acting antiviral (DAA) therapy (Sofosbuvir/Daclatasvir). Sustained virological response was evaluated at 12 weeks post-treatment (SVR12). Results Overall, from 3485 participants, 182 (5.2%) and 117 (3.4%) tested positive for HCV antibody and RNA, respectively. Among 116 patients who were eligible for treatment, 24% (n = 28) were released before treatment and 72% (n = 83) initiated DAA therapy, of whom 81% (n = 67/83) completed treatment in prison, and the rest were released. Of total released patients, 68% (n = 30/44) were linked to care in community, and 70% (n = 21/30) completed treatment, including 60% (n = 12/20) and 90% (n = 9/10) among those who were released before and during treatment, respectively. The overall HCV treatment uptake and completion were 89% (n = 103/116) and 85% (n = 88/103), respectively. From people who completed treatment, 43% (n = 38/88) attended for response assessment and all were cured (SVR12 = 100%). Conclusions Integrated HCV care models are highly effective and can be significantly strengthened by post-release interventions. The close collaboration of community and prison healthcare systems is crucial to promote high levels of treatment adherence. Future studies should investigate the predictors of engagement with HCV care following release.

Context: Pain management is essential for all patients, including those with liver diseases. Opiates should be used with caution in patients with liver diseases as they are well-known for constipation, sedation, and precipitation of encephalopathy. Meanwhile, the principal fear of the use of non-steroidal anti-inflammatory drugs (NSAIDs) in liver disease is the danger of hastening renal impairment. Thus, acetaminophen is considered first-line therapy because of the side effects of other analgesics. However, there is an assumption that patients with chronic liver disease may be in danger when consuming the drug at therapeutic doses. Methods: Data were extracted from 33 papers. All articles were published until July 2020. The search was done using the following keywords: acetaminophen, paracetamol, cirrhosis, liver disease, chronic hepatitis, and safety in reliable databases. A total of 414 articles were selected some of which were excluded owing to irrelevance, studies on animals and the lack of access to the full text. Results: Cirrhotic patients could safely take acetaminophen in adjusted doses. Although acetaminophen was safely administered in therapeutic doses in alcoholic patients, there were reports of hepatotoxicity even in therapeutic doses. Acetaminophen was not recommended in patients with acute hepatitis but could be safely used in patients with chronic hepatitis. Patients with non-alcoholic fatty liver disease (NAFLD) were susceptible to acetaminophen toxicity. Conclusions: In spite of the conception that acetaminophen has dire consequences in liver disease, it can be safely administered in adjusted doses in most liver diseases.

Context: Within only 30 days after the first announcement of infection with “SARS-CoV-2” in Wuhan, it spread to more than 20 countries and become a pandemic by WHO as a “high alarming level of infection” with 136,343 involved cases all over the world. Methods: To uncover more about the probable gastrointestinal transmission and its clinical manifestations, we reviewed all research publications with keywords including: “COVID-19”, “SARS-CoV-2”, “Coronavirus”, “outbreak”, “ARAS-CoV” in Medline, Scopus, Google Scholar as well as all news in social media about “novel COVID-19 pandemic”. Out of 40 recent publications, 10 articles were studied by 2 authors. Results: Although the SARS-CoV-2 tends to infect respiratory epithelial cells through the respiratory tracts, recent investigations detected the virus in the stool specimen, raising the question of the fecal-oral transmission route. Different studies showed that almost all gastrointestinal signs and symptoms were seen in elderly patients (more than 65 years old). including anorexia (40%), nonspecific abdominal pains (8%), diarrhea (10%) and nausea and Vomiting in about 8% of patients. Anorexia and generalized abdominal pain suffer many treated cases even 10 - 20 days after negative blood tests (like CRP, lymphopenia) and negative PCR of respiratory samples. The main reason for this prolonged anorexia and abdominal pain may be due to the long persistence of COVID-19 in the gastrointestinal tracts after primary treatment. Conclusions: Comparing to SARS, patients with COVID-19 showed less diarrhea, nausea, vomiting and/or abdominal discomfort before respiratory symptoms. Feces as a potential contagious source of Viral RNA can last even after viral clearance in the respiratory tract. We strongly recommend all cured patients of COVID-19 to disinfect and clean their toilets until 17 - 20 days after negative blood tests and solving their respiratory disorders. Gastrointestinal manifestations have seen in all men while no women referred with GI signs.

ContextHepatitis D virus (HDV) infection, as the main coinfection in patients with chronic hepatitis B, leads to progressive liver disease. Elucidating the global distribution of HDV genotypes may be beneficial for the development of HDV vaccines and antiviral agents.ObjectivesThrough this systematic review, we aimed to present a clear picture of HDV genotype dispersal at the global and regional levels.MethodsA systematic search was performed in Scopus, PubMed, and Web of Science using the relevant keywords of hepatitis D and HDV genotype. The old HDV genotype classification (HDV I, II, and III) and African HDV genotypes (HDV-5, -6, -7, and -8) were used for showing the HDV genetic dispersion. The data of the country-level distribution of HDV genotypes were translated to the regional and global distributions of HDV genotypes.ResultsAmong all 1,318 unique titles, 71 studies were screened in the qualitative synthesis consisting of 77 records from 33 countries (sampling locations). In Africa, themost common genotype was HDV I, followed by African HDV genotypes. In Asia, themost frequent genotype was HDV II, followed by HDV I. In Europe and Oceania, the most common HDV genotype was HDV I, followed by HDV II and African genotypes. In the Middle East and North America, the most frequent HDV genotype was HDV I. In South America, the most common HDV genotype was HDV III, followed by HDV I and African genotypes.ConclusionsWe found HDV I is distributed globally. Other HDV genotypes are observed regionally: HDV II mainly in East Asia, HDV III exclusively in South America, and African genotypes mainly in West Africa.

Non-alcoholic fatty liver disease (NAFLD) is growing in prevalence globally and no definitive evidence for any approved pharmacological approaches for patients with NAFLD has been found yet. This study was aimed to assess the clinical effects of flaxseed and hesperidin in patients with NAFLD. In this randomized, controlled, clinical trial, one hundred eligible patients with NAFLD were enrolled and randomly assigned to four dietary intervention groups including lifestyle modification program (control), lifestyle modification program with 30 g whole flaxseed powder, lifestyle modification program with 1 g hesperidin supplementation, and lifestyle modification program with combination of 30 g flaxseed and 1 g hesperidin (flax-hes) for 12 weeks. The changes in anthropometric parameters, metabolic profiles of glucose and lipids, inflammatory biomarkers and hepatic steatosis and fibrosis were evaluated. After the 12-week dietary interventions, significant reductions in body mass index, glucose hemostasis parameters and hepatic steatosis were observed in all groups. Repeated measures analysis of variance revealed a significant effect for time relative to almost all paraclinical parameters. Post hoc analysis with Bonferroni correction revealed that the three intervention groups experienced significant decreases in plasma levels of alanine aminotransferase, indices of insulin resistance and insulin sensitivity, fasting glucose and fatty liver index compared to control (p

Background: Hepatitis E virus (HEV) infection is an important emerging health issue in patients on hemodialysis (HD). To date, numerous studies have reported controversial findings regarding the seroprevalence of HEV among this high-risk group around the world. The aim of the present study was to estimate the overall seroprevalence of HEV in HD patients.Methods: A systematic literature search was carried out using PubMed, Web of Science, Scopus, Embase, and Google scholar from inception to January 10, 2020 with standard keywords. Pooled seroprevalence estimates with 95% confidence intervals (CI) were calculated using a random intercept logistic regression model.Results: A total of 56 studies met the inclusion criteria compromising 9483 HD patients. The pooled seroprevalence of HEV was estimated 9.31% (95%CI: 6.83%-12.57%). The seroprevalence of HEV was increased from 6.6% between the years of 1994 and 2000 to 11.13% from the year of 2016 to 2020. Blood transfusion was associated with a nearly two-fold increase in the rate of HEV seropositivity (OR=1.99; 95%CI: 1.50-2.63, P value < 0.0001, I2=6.5%).Conclusions: Our results indicated an increased exposure of HD patients with HEV infection over the last decade. We concluded that blood transfusion, age and duration of HD are considerable risk factors for acquiring HEV infection among HD patients.