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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)

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.

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.

Background Given the increasing prevalence of non-alcoholic fatty liver disease, it is necessary to find an easy and cost-effective method in its management and treatment. Probiotics are a group of living microorganisms that might affect NAFLD through the intestinal-liver axis. The present clinical trial aims to examine the effect of probiotic yogurt consumption on liver enzymes, steatosis and liver fibrosis in patients with NAFLD. Methods Sixty-eight patients with NAFLD will be recruited in this study. After block matching for sex, BMI and age, patients will be randomly assigned to receive 300 g/d probiotic yogurt containing 106 cfu/g of Lactobacillus acidophilus and Bifidobacterium lactis strains or 300 g/d plain yogurt daily for 12 weeks and those in the control group would receive similar amounts of plain yogurts. Weight, height, and waist circumference will be measured at study baseline and after the intervention. Biochemical indicators including plasma glucose, serum insulin, lipid profile, liver markers (ALT, AST and GGT) will be examined at study baseline and at the end of the trial. Insulin resistance and insulin sensitivity will be determined using the HOMA-IR and QUICKI equation. The degree of steatosis and hepatic fibrosis will also be assessed at the beginning and end of the intervention by the same gastroenterologist using elastography with fibroscan. Discussion Probiotics have been suggested as a new strategy in the management of NAFLD. Their effects might be mediated through intestinal microbiota modification and production of short-chain fatty acids. Consumption of probiotic-enriched foods, rather than their supplements, might be a cost-effective method for long-term use in these patients. In case of finding the beneficial effects of probiotic yogurt consumption in the current clinical trial, its inclusion in the dietary plan of NAFLD patients can be recommended. Trial registration This clinical trial was registered in Iranian Registry of Clinical Trials (www.irct.ir) at 2021-04-19 with code number of IRCT20210201050210N1.

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.

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.

Hepatocellular carcinoma (HCC) is one of the high-metastatic types of cancer, and metastasis occurs in one-third of patients with HCC. To maintain the effectiveness of drug compounds on cancer cells and minimize their side effects on normal cells, it is important to use new approaches for overcoming malignancies. Immunotoxins (ITs), an example of such a new approach, are protein-structured compounds consisting of toxic and binding moieties which can specifically bind to cancer cells and efficiently induce cell death. Here, we design and scrutinize a novel immunotoxin against an oncofetal marker on HCC cells. We applied a truncated diphtheria toxin (DT389) without binding domain as a toxin moiety to be fused with a humanized YP7 scFv against a high-expressed Glypican-3 (GPC3) antigen on the surface of HCC cells. Cytotoxic effects of this IT were investigated on HepG2 (GPC3+) and SkBr3 (GPC3−) cell lines as positive- and negative-expressed GPC3 antigens. The dissociation constant (Kd) was calculated 11.39 nM and 18.02 nM for IT and YP7 scfv, respectively, whereas only IT showed toxic effects on the HepG2 cell line, and decreased cell viability (IC50 = 848.2 ng/mL). Changing morphology (up to 85%), cell cycle arrest at G2 phase (up to 13%), increasing intracellular reactive oxygen species (ROSs) (up to 50%), inducing apoptosis (up to 38% for apoptosis and 23% for necrosis), and an almost complete inhibition of cell movement were other effects of immunotoxin treatment on HepG2 cells, not on SkBr3 cell line. These promising results reveal that this new recombinant immunotoxin can be considered as an option as an HCC inhibitor. However, more extensive studies are needed to accomplish this concept.

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Therefore, fighting against such cancer is reasonable. Chemotherapy drugs are sometimes inefficient and often accompanied by undesirable side effects for patients. On the other hand, the emergence of chemoresistant HCC emphasizes the need for a new high-efficiency treatment strategy. Immunotoxins are armed and rigorous targeting agents that can purposefully kill cancer cells. Unlike traditional chemotherapeutics, immunotoxins because of targeted toxicity, insignificant cross-resistance, easy production, and other favorable properties can be ideal candidates against HCC. In this review, the characteristics of proper HCC-specific biomarkers for immunotoxin targeting were dissected. After that, the first to last immunotoxins developed for the treatment of liver cancer were discussed. So, by reviewing the strengths and weaknesses of these immunotoxins, we attempted to provide keynotes for designing an optimal immunotoxin against HCC.

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 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.

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.

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.

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

Previous local and national Iranian publications indicate that all Iranian hepatitis B virus (HBV) strains belong to HBV genotype D. The aim of this study was to analyze the evolutionary history of HBV infection in Iran for the first time, based on an intensive phylodynamic study. The evolutionary parameters, time to most recent common ancestor (tMRCA), and the population dynamics of infections were investigated using the Bayesian Monte Carlo Markov chain (BMCMC). The effective sample size (ESS) and sampling convergence were then monitored. After sampling from the posterior distribution of the nucleotide substitution rate and other evolutionary parameters, the point estimations (median) of these parameters were obtained. All Iranian HBV isolates were of genotype D, sub-type ayw2. The origin of HBV is regarded as having evolved first on the eastern border, before moving westward, where Isfahan province then hosted the virus. Afterwards, the virus moved to the south and west of the country. The tMRCA of HBV in Iran was estimated to be around 1894, with a 95% credible interval between the years 1701 and 1957. The effective number of infections increased exponentially from around 1925 to 1960. Conversely, from around 1992 onwards, the effective number of HBV infections has decreased at a very high rate. Phylodynamic inference clearly demonstrates a unique homogenous pattern of HBV genotype D compatible with a steady configuration of the decreased effective number of infections in the population in recent years, possibly due to the implementation of blood donation screening and vaccination programs. Adequate molecular epidemiology databases for HBV are crucial for infection prevention and treatment programs.

Killer cell immunoglobulin like receptors (KIRs) have a principal role in regulating the effector functions of NK cells, particularly in viral infections. The major ligands for KIRs are human leukocyte antigen (HLA) class I molecules. The aim of this study is to investigate the possible association of KIR genes, their known HLA ligands and compound KIR–HLA genotypes with hepatitis B virus (HBV) infection. Our study group consisted of 202 Iranian HBV-infected patients (52 spontaneously recovered, 50 asymptomatic carriers, 50 chronic sufferers and 50with liver cirrhosis) and 100 ethnic-matched healthy control subjects. KIR and HLA genotyping was performed by a polymerase chain reaction–sequence-specific primer (PCR–SSP). The frequencies of the KIR2DL5A, KIR2DS1, and KIR3DS1 genes were significantly elevated in recovered individuals when compared with both control and patient groups. Also, KIR2DL5, and KIR3DP1 full were escalated in recovered individuals in comparison with patient groups. In addition, HLA-Bw4 ligand and HLA-A Bw4 were highly frequent in recovered individuals compared with healthy controls. Furthermore, the KIR3DS1 + HLA-Bw4, KIR3DS1 + HLA-Bw4 Iso80 , and KIR3DS1 + HLA-A Bw4 genotypes were significantly more common in recovered individuals than both healthy control and patient groups. Interestingly, AA genotype had less frequency and Bx had higher frequency in recovered individuals compared with both healthy control and patient groups. Our findings suggest a potential impact of the NK cells’ activating phenotype that leads to the HBV clearance in infected individuals.

Few studies have focused on the effects of a soy containing diet on inflammation and serum leptin level among patients with nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to determine the effects of such a diet in patients with NAFLD. Forty-five patients with NAFLD participated in this parallel randomized clinical trial for 8 weeks. Patients were randomly allocated to these 3 groups: 1) a low-calorie diet, 2) low-calorie low-carbohydrate diet, and 3) low-calorie low-carbohydrate soy containing diet. Low-calorie low-carbohydrate soy containing diet reduced fasting blood sugar (FBS) and serum insulin level significantly compared to other 2 groups (−11.6±2.8 vs. −6.3±1.7 and −3.1±1.0 mg/dl for FBS; and −5.1±1.2 vs. −1.2±0.3 and −1.7±0.5 mg/dl for serum insulin level). Serum hs-CRP level was also reduced significantly following low-calorie low-carbohydrate soy containing diet (−0.8±0.1 vs. −0.1±0.06 and −0.1±0.06 mg/dl). Both systolic and diastolic blood pressures were reduced significantly. Changes in leptin level tended to be different among 3 groups. After trial, 5 patients in each intervention group did not have NAFLD. From 6 patients in grade 2 at the beginning only 1 patient remained and others moved to grade 1. Low-calorie low-carbohydrate soy containing diet could reduce glycemic indices, hs CRP, systolic and diastolic blood pressure in a significant level in patients with NAFLD. However, these effects were dependent on baseline weight and further studies are needed to clarify the effect of such interventions in subjects with different BMI categories.

Introduction Toll like receptor 4 (TLR4) is an extracellular pathogen recognition receptor (PRR) which recognizes a wide range of pathogens and damage associated molecular patterns (PAMPs and DAMPs). It can activate intracellular signaling and consequently transcription factors which participate in transcription from either immune related or malignancy genes. Thus, it has been hypothesized that TLR4 may be a cause of hepatocellular carcinoma (HCC). This article has reviewed the roles of TLR4 in the pathogenesis of HCC. Method “TLR4”, “hepatocellular carcinoma”, “liver tumor” and “liver cancer” were used as key words for searching in Scopus, Google Scholar and MEDLINE scientific databases. Results Most of the investigations documented the roles of TLR4 in induction of HCC via several mechanisms including increased number of T regulatory lymphocytes and liver resident follicular helper like cells, increased production of pro-inflammatory and malignancy related molecules including cytokines, NANOG, Caspase-1, Ephrin-A1, NO and BCL6. TLR4 participates in the proliferation of the cells and also production of the molecules in both chronic infectious and non-infectious inflammatory diseases. Discussion TLR4 is an innate immunity receptor which plays a pathogenic role during chronic inflammation and can induce HCC in human.

Background/aims In the Middle East (ME), the proper understanding of hepatitis, especially viral hepatitis, is considered to be extremely important. However, no published paper has investigated the status of hepatitis-related research in the ME. A scientometric analysis based on the Web of Science database was conducted on hepatitis-related papers in the ME to determine the current status of research on this topic. Materials and methods A scientometric analysis using the Web of Science database, specifically articles from the Expanded Science Citation Index and Social Sciences Citation Index, was conducted on work published between 2005 and 2014 using the keyword "hepatitis" in conjunction with the names of countries in the ME. Results Of 103,096 papers that used the word "hepatitis" in their title, abstract, or keywords, only 6,540 papers (6.34%) were associated with countries in the ME. Turkey, Iran, Egypt, Israel, and Saudi Arabia were the top five countries in which hepatitis-related papers were published. Most papers on hepatitis A, B, and D and autoimmune hepatitis were published in Turkey, and most papers on hepatitis C were published in Egypt. Conclusion We believe that both the quantity and the quality of hepatitis-related papers in this region should be improved. Implementing multicenter and international research projects, holding conferences and congress meetings, conducting educational workshops, and establishing high-quality medical research journals in the region will help countries in the ME address this issue effectively.

Background: The IFNL4 rs368234815 polymorphism plays a prominent role in spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. This study aimed to develop a polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method for assessment of rs368234815 polymorphism. Methods: We genotyped the rs368234815 polymorphism in 87 patients with chronic HCV by PCR sequencing and PCR-RFLP methods, simultaneously. Results: Genotyping of IFNL4 rs368234815 via PCR-RFLP was concordant with PCR sequencing in all 87 individuals (100%). The analytical sensitivity and specificity of the developed PCR-RFLP method for genotyping of rs368234815 polymorphism were each 100%. Among these patients with chronic HCV, the frequency of rs368234815 TT/TT, TT/ΔG, and ΔG/ΔG were 44.8%, 37.9%, and 17.3%, respectively. Conclusions: The PCR-RFLP method that we developed is accurate, rapid, inexpensive, and easy to perform for genotyping of the IFNL4 rs368234815 polymorphism. This method can be used for clinical and research work. * Abbreviations : HCV : hepatitis C virus PEG-IFN : pegylated interferon RBV : ribavirin DAAs : direct-acting antivirals IFNL4 : interferon lambda 4 bp : base pair PCR-RFLP : polymerase chain reaction–restriction fragment length polymorphism RE : restriction endonuclease IFNL2 : interferon lambda 2 IFNL3 : interferon lambda 3 RS : restriction site SVR : sustained virologic response SNPs : single nucleotide polymorphisms LD : linkage disequilibrium HRM : high resolution melting TM : Melting Temperature

ispartof: LANCET GASTROENTEROLOGY & HEPATOLOGY vol:4 issue:8 pages:581-582 ispartof: location:Netherlands status: published

Blood-borne viruses including Hepatitis B and C, HIV, HTLV-1 and parvovirus B19 are still a factor of concern, especially for hemophilia patients. Although the safety of the blood supply continues to improve worldwide, the blood supply system in Afghanistan was damaged by many years of conflict and political instability. To date, there are few studies focused on the prevalence of blood-borne viruses in hemophilia patients. This study is first to investigate the prevalence of five blood-borne viruses in Afghanistan hemophilia patients in four cities including Kabul, Herat, Mazar-i-Sharif and Jalal Abad. A total of 80 hemophilia male patients were screening for the presence of five transfusion-transmitted viruses using ELISA and PCR. Data obtained showed 2.5% seropositivity for HBV, 8.75% seropositivity for HCV, and 91.25% seropositivity for parvovirus B19. None of the patients were positive for HIV and HTLV-1 and the prevalence of HCV was higher in older patients rather than younger patients. This finding, the first to report in Afghanistan, shows a high prevalence of parvovirus B19 in Afghanistan hemophilia patients and implementation of highly sensitive screening is necessary.

Background Despite the reported health effects of cardamom on dyslipidemia, hepatomegaly, and fasting hyperglycemia, no human research has studied its potency in non-alcoholic fatty liver disease (NAFLD) as the hepatic part of metabolic syndrome. Our aim was determining the effects of green cardamom (GC) on serum glucose indices, lipids, and irisin level among overweight or obese NAFLD patients. Methods The place of participant recruitment was the polyclinic of the National Iranian Oil Company (NIOC) central hospital in Tehran. Based on the ultrasonography and eligibility criteria, 87 participants were randomly divided into two groups as cardamom (n = 43) or placebo (n = 44). The supplementation was two 500 mg capsules 3 times/day with meals for 3 months. Serum irisin, fasting blood sugar (FBS), insulin (FBI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were measured. Quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment-insulin resistance (HOMA-IR) were also calculated. Results In comparison with placebo, GC significantly increased irisin, HDL-c, and QUICKI and decreased FBI, TG, LDL-c, HOMA-IR, and the grade of fatty liver (P 0.05). Conclusion GC supplement improved the grade of fatty liver, serum glucose indices, lipids, and irisin level among overweight or obese NAFLD patients. The changes in these biomarkers may yield beneficial effects on NAFLD. Further trials on the efficacy of GC for clinical practice are suggested. Trial registration Iranian Registry of Clinical Trials, IRCT2015121317254N4. Registered 27/12/2015, Electronic supplementary material The online version of this article (10.1186/s12906-019-2465-0) contains supplementary material, which is available to authorized users.

This study aimed to evaluate the effects of hesperidin on nonalcoholic fatty liver disease (NAFLD) characteristics. In this randomized, double-blind, controlled clinical trial, 50 NAFLD patients were supplemented with either 1-g hesperidin capsule or identical placebo capsule for 12 weeks. During the intervention, both groups were advised to follow healthy lifestyle habits including dietary and physical activity recommendations. At the end of the study, hesperidin supplementation, compared with placebo, was associated with a significant reduction in alanine aminotransferase (p = .005), γ-glutamyltransferase (p = .004), total cholesterol (p = .016), triglyceride (p = .049), hepatic steatosis (p = .041), high-sensitivity C-reactive protein (p = .029), tumor necrosis factor-α, and nuclear factor-κB (NF-κB). In conclusion, our results indicate that hesperidin supplementation accompanied with lifestyle modification is superior to lifestyle modification alone in management of NAFLD at least partially through inhibiting NF-κB activation and improving lipid profile. Further studies with higher dose of hesperidin are required to find the optimal dose.

Purpose: There are only a few measures to assess quality of life among patients with liver disorders. The aim of this study was to determine the psychometric properties of the Liver Disease Symptom Index Version 2.0 (LDSI 2.0), a disease specific measure of health-related quality of life (HRQOL), in Persian-speaking patients with chronic hepatitis B. Method: Using a cross-sectional design, 312 patients were recruited. Data were collected from the patients using the LDSI 2.0, Chronic Liver Disease Questionnaire, and EuroQol. Convergent and discriminant validity were investigated. Known-groups validity and factor structure of the scale were also determined. Receiver operating characteristics was used to discriminate patients based on their general health status. Results: Significant correlations were found between HRQOL measures. Disease duration, disease stage, and serum aspartate aminotransferase differentiated patients. Factor analysis determined a seven-factor solution that explained 70% of the total variance. Area under the curve in receiver operating characteristics analysis was 0.706; 95% confidence interval = [0.648, 0.764]. Conclusions: The LDSI2.0 is an appropriate HRQOL scale for use among Iranian patients with chronic hepatitis B based on its solid psychometric properties in this population.

Background and aim. The combination of Sofosbuvir (SOF) and Ledipasvir (LDV) has been lead to considerable enhancement of treatment of hepatitis C virus (HCV) genotype 1 infection. A meta-analysis of the currently available studies was undertaken with the aim to evaluate the antiviral efficacy of SOF/LDV therapy for 12 or 24 weeks with or without Ribavirin (RBV) in patients with HCV genotype 1 infection. Material and methods. In this meta-analysis, we searched databases including PubMed, Scopus, Science Direct and Web of Science using appropriate keywords. All papers which evaluated the efficacy of combination therapy of SOF/LDV with or without RBV for 12 or 24 weeks among patients with HCV genotype 1 infection were included. Results. The 20 published articles were assessed for eligibility and finally 10 articles pooling 2248 participants were included in this meta-analysis. Pooled SVR12 for four SOF/LDV regimens were 95% (95%CI = 93%-97%) for 12 weeks of treatment with SOF/LDV, 97% (95%CI = 95%-98%) for 24 weeks of treatment with SOF/LDV, 96% (95%CI = 94%-97%) for 12 weeks of treatment with SOF/ LDV/RBV and 98% (95%CI = 97%-99%) for 24 weeks of treatment with SOF/LDV/RBV. Only in treatment regimen of SOF/LDV for 12 weeks, cirrhosis had a significant effect on the SVR12 (OR = 0.21, 95%CI = 0.07-0.66). Furthermore, NS5A resistance-associated substitutions at baseline were associated with decrease in the rate of SVR (OR = 0.31, 95%CI = 0.2-0.5). Conclusions. The Interferon-free regimen of SOF/LDV for 12 or 24 weeks with or without RBV is highly effective for treatment of patients with HCV genotype 1 infection.

The aim was to investigate the effect of hepatitis C virus (HCV) infection treatment with direct-acting antiviral (DAA) drugs on patients' mood, sleep quality and quality of life (QoL).Chronic HCV-infected patients receiving DAAs were evaluated prospectively. Patients were evaluated before the beginning of treatment and 12-24 weeks after finishing their treatment duration using the Pittsburgh Sleep Quality Index, Beck depression inventory questionnaire and SF-36 health-related QoL questionnaires.A total of 120 patients with a mean age of 41.03 ± 7.68 years were evaluated (68.3% males). The mean follow-up duration was 141.79 ± 27.88 days after finishing the treatment. Significant improvement in the scores of sleep quality (5.13 ± 1.5 vs. 3.43 ± 1.35), mood (12.77 ± 4.02 vs. 9.27 ± 3.14) and QoL (77.49 ± 5.15 vs. 83.95 ± 3.39) post treatment compared with pretreatment were observed (p 0.05). Changes in patients' sleep and mood were not related to their QoL change (p 0.05).DAAs for the treatment of HCV have a significant effect on improving their sleep, mood and QoL. The changes in sleep quality, mood and QoL of patients were independent and were not affected by each other.

BACKGROUND/AIMS: Mother-to-child transmission (MTCT) is a common transmission mode of hepatitis B virus (HBV). It has been shown that the infection may occur in some infants despite the use of immunoprophylaxis, and many studies have demonstrated the efficacy of antivirals such as lamivudine to reduce such events. MATERIALS AND METHODS: A meta-analysis was conducted concerning the efficacy and safety of lamivudine during pregnancy, in the prevention of vertical transmission of HBV infection. Studies were identified by searching various databases up to January 2016 for variations of the following phrase: “lamivudine AND (pregnancy or pregnant) AND (HBV or hepatitis).” Subjects who had received lamivudine were included in the case group, and those who had not were included in the control group. RESULTS: Our search identified a total number of 881 citations, of which 25 studies (with a total number of 2,667 pregnant women) were included in the meta-analysis. The analysis showed a significant difference between the seropositive HBsAg infants from the case and control groups (RR= 16.97, 95% confidence interval 8.36–34.45), which is the most critical factor in determining the MTCT of HBV. No significant difference was reported between the prevalence of side effects in the case and control groups. CONCLUSION: This meta-analysis strongly suggests the use of lamivudine in the prevention of HBV vertical transmission in carrier pregnant women with the HBV DNA levels greater than 10(6) copies/mL. And for women with the HBV viral loads lower than 10(6) copies/mL, we suggest clinicians to examine the use of lamivudine on a case-to-case basis, noting that lamivudine seems to be a safe drug for the mother and the fetus.

Background Hepatitis C virus (HCV) point-of-care testing using rapid diagnostic test (RDT) is the solution for large-scale, feasible, fast and reliable screening of HCV infection. Objectives The aim of this study was to evaluate the diagnostic performance of HCV RDT for screening of HCV infection in a real-life prison setting. Study design This study was conducted on individuals admitted and incarcerated in the Central Prison of Karaj, 2017–2018. For all inmates, anti-HCV testing using a RDT on finger-stick blood in the prison and ELISA at the laboratory were performed. For evaluation of reproducibility, more than 1000 cases were recruited for re-evaluation of the HCV RDT using anticoagulated blood in the laboratory. Results Among 1788 participants, 76 (4.25%) and 106 (5.93%) were positive for anti-HCV using RDT and ELISA, respectively. Among 34 cases with discordant results using the RDT and ELISA, 17 were the result of testing error in prison, 7 false positive of ELISA and 10 false negative of RDT in individuals with HCV spontaneous clearance. The sensitivity of the RDT with inclusion of testing error in prison for detection of anti-HCV was 75%. However, with exclusion of testing error in prison and considering HCV RNA as the reference method for diagnosis of current HCV infection the sensitivity reached 100%. The RDT was 100% reproducible using both evaluations in prison and the laboratory. Conclusions The RDT is a reliable and feasible method for screening of anti-HCV in settings such as a prison. However, the testing should be performed in a standard procedure to have the optimal diagnostic performance.

People from low-to-middle income countries have been migrating to western Europe on a large scale in recent years. Data indicate that the number of first-time asylum applications by non-EU members increased from 290 000 in 2011 to more than 1·3 million in 2015. During the peak period of migration, The Global Health Sector Strategy on Viral Hepatitis was adopted by WHO. Viral hepatitis, and particularly hepatitis B virus (HBV), is an important disease because of its high prevalence and associated mortality. In some cases, HBV can be carried by refugees arriving from regions of high and intermediate prevalence. Refugees with HBV might not show clinical symptoms and not be diagnosed in destination countries with a low prevalence, where screening is not regularly done. Although transmission to the host population is low, dedicated surveillance and tailored public health policies are required. It is important to note that some of the countries that receive many migrants do not have a universal HBV vaccination programme. In this Viewpoint, we argue that the current large-scale movement from regions with high or intermediate HBV prevalence should be taken as an opportunity to achieve viral hepatitis elimination targets, by establishing a well prepared infrastructure for HBV screening, vaccination, and treatment., SCOPUS: no.j, info:eu-repo/semantics/published

BACKGROUND & AIMS: Hepatitis D virus (HDV) superinfection in patients with hepatitis B virus (HBV) is associated with rapid progression to liver cirrhosis and hepatocellular carcinoma. Treatment options are limited, and no vaccine is available. Although HDV-specific CD8(+) T cells are thought to control the virus, little is known about which HDV epitopes are targeted by virus-specific CD8(+) T cells or why these cells ultimately fail to control the infection. We aimed to define how HDV escapes the CD8(+) T-cell–mediated response. METHODS: We collected plasma and DNA samples from 104 patients with chronic HDV and HBV infection at medical centers in Europe and the Middle East, sequenced HDV, typed human leukocyte antigen (HLA) class I alleles from patients, and searched for polymorphisms in HDV RNA associated with specific HLA class I alleles. We predicted epitopes in HDV that would be recognized by CD8(+) T cells and corresponded with the identified virus polymorphisms in patients with resolved (n = 12) or chronic (n = 13) HDV infection. RESULTS: We identified 21 polymorphisms in HDV that were significantly associated with specific HLA class I alleles (P < .005). Five of these polymorphisms were found to correspond to epitopes in HDV that are recognized by CD8(+) T cells; we confirmed that CD8(+) T cells in culture targeted these HDV epitopes. HDV variant peptides were only partially cross-recognized by CD8(+) T cells isolated from patients, indicating that the virus had escaped detection by these cells. These newly identified HDV epitopes were restricted by relatively infrequent HLA class I alleles, and they bound most frequently to HLA-B. In contrast, frequent HLA class I alleles were not associated with HDV sequence polymorphisms. CONCLUSIONS: We analyzed sequences of HDV RNA and HLA class I alleles that present epitope peptides to CD8(+) T cells in patients with persistent HDV infection. We identified polymorphisms in the HDV proteome that associate with HLA class I alleles. Some variant peptides in epitopes from HDV were only partially recognized by CD8(+) T cells isolated from patients; these could be mutations that allow HDV to escape the immune response, resulting in persistent infection. HDV escape from the immune response was associated with uncommon HLA class I alleles, indicating that HDV evolves, at the population level, to evade recognition by common HLA class I alleles.

Introduction Resistance-associated substitutions (RASs) in the NS5A gene of hepatitis C virus (HCV) has been studied as one of the predictors of response to NS5A inhibitor-containing regimens. This study aimed to evaluate the prevalence of pre-treatment naturally-occurring NS5A RASs in HCV isolates from patients with chronic HCV genotype 1 (HCV-1) infection retrieved from GenBank. Methods In the search procedure, the studies with published HCV-1 NS5A sequence in GenBank were screened and evaluated for inclusion in the pooled analysis. The sequences of the included studies were retrieved from GenBank and evaluated for substitutions in amino acid positions24, 26, 28, 29, 30, 31, 32, 38, 58, 62, 92 and 93 of HCV NS5A including RASs and RASs conferring >100 resistance fold change (RASs >100X). Results In the pooled analysis, 2409 isolates from patients with HCV-1 infection were included, consisting 1305 (54.2%) HCV-1a and 1104 (45.8%) HCV-1b isolates. The prevalence of NS5A RASs and RASs >100X were 16.0% (95%CI = 14.6%–17.5%) and 4.7% (95%CI = 3.9%–5.6%), respectively. The NS5A RASs were more frequently observed in HCV-1b isolates than in HCV-1a isolates (P Conclusion The naturally-occurring HCV NS5A RASs especially those with clinical relevance (RASs >100X) are observed in a small (4.7%) number of patients with HCV-1 infection.

Virus-specific CD8 T cell response seems to play a significant role in the outcome of hepatitis delta virus (HDV) infection. However, the HDV-specific T cell epitope repertoire and mechanisms of CD8 T cell failure in HDV infection have been poorly characterized. We therefore aimed to characterize HDV-specific CD8 T cell epitopes and the impacts of viral mutations on immune escape. In this study, we predicted peptide epitopes binding the most frequent human leukocyte antigen (HLA) types and assessed their HLA binding capacities. These epitopes were characterized in HDV-infected patients by intracellular gamma interferon (IFN-γ) staining. Sequence analysis of large hepatitis delta antigen (L-HDAg) and HLA typing were performed in 104 patients. The impacts of substitutions within epitopes on the CD8 T cell response were evaluated experimentally and by in silico studies. We identified two HLA-B*27-restricted CD8 T cell epitopes within L-HDAg. These novel epitopes are located in a relatively conserved region of L-HDAg. However, we detected molecular footprints within the epitopes in HLA-B*27-positive patients with chronic HDV infections. The variant peptides were not cross-recognized in HLA-B*27-positive patients with resolved HDV infections, indicating that the substitutions represent viral escape mutations. Molecular modeling of HLA-B*27 complexes with the L-HDAg epitope and its potential viral escape mutations indicated that the structural and electrostatic properties of the bound peptides differ considerably at the T cell receptor interface, which provides a possible molecular explanation for the escape mechanism. This viral escape from the HLA-B*27-restricted CD8 T cell response correlates with a chronic outcome of hepatitis D infection. T cell failure resulting from immune escape may contribute to the high chronicity rate in HDV infection. IMPORTANCE Hepatitis delta virus (HDV) causes severe chronic hepatitis, which affects 20 million people worldwide. Only a small number of patients are able to clear the virus, possibly mediated by a virus-specific T cell response. Here, we performed a systematic screen to define CD8 epitopes and investigated the role of CD8 T cells in the outcome of hepatitis delta and how they fail to eliminate HDV. Overall the number of epitopes identified was very low compared to other hepatotropic viruses. We identified, two HLA-B*27-restricted epitopes in patients with resolved infections. In HLA-B*27-positive patients with chronic HDV infections, however, we detected escape mutations within these identified epitopes that could lead to viral evasion of immune responses. These findings support evidence showing that HLA-B*27 is important for virus-specific CD8 T cell responses, similar to other viral infections. These results have implications for the clinical prognosis of HDV infection and for vaccine development.

Patients with thalassemia may also have cardiac abnormalities due to congenital problems, anemia, and increased burden of iron in their myocardium. This study was designed to evaluate the effects of direct acting antiviral (DAA) therapy on the cardiac function of hepatitis C virus (HCV)-infected patients with thalassemia.HCV-infected thalassemia patients were enrolled to this prospective evaluation. Daily tablets of 90 mg Ledipasvir (or 60 mg Daclatasvir) plus 400 mg Sofosbuvir (±ribavirin) were prescribed for the patients according to the Iran Hepatitis Network's guidelines. An echocardiography fellow collected the echocardiography findings before and after the treatment of all the patients. The patients were followed up for any cardiac events within 12 weeks after finishing the treatment.Thirty-two patients with the mean age of 24.2 ± 6.4 years were evaluated. All patients showed a sustained virological response at the 12th week after finishing the treatment. The patients' left ventricular end systolic diameter (3.0 vs 3.24; P = 0.003) and volume (33.8 vs 43.6; P = 0.001), global longitudinal strain of the left ventricle (-22.0 vs -20.6, P = 0.046), and average (-21.4 vs -20.3; P = 0.048), and the right ventricle size (3.12 vs 3.31; P = 0.012) were significantly increased after finishing the treatment. Changes in the abovementioned parameters were not correlated with the patients' myocardium iron load. There were no significant differences in other echocardiographic parameters ( P 0.05) before and after the treatment.Sofosbuvir-based regimens for HCV treatment were safe for our HCV-infected patients with thalassemia. Our patients' ejection fraction remained unchanged. Hence, more specialized echocardiographic evaluations were recommended for those with a history of cardiac abnormalities, cardiac iron overload, and in case of any cardiac adverse event during DAA therapy in patients with thalassemia.

Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide and late diagnosis is the main cause of death in HCC patients. In this study expression patterns of HSP70, GPC3 and GS and their relationships with pathogenesis of HCC in Iranian patients were investigated. The expression of HSP70, GPC3 and GS were determined by immunohistochemistry and quantitative real-time PCR (q-PCR) methods, using 121 cases from patients with HBV alone, HCC without HBV, HBV+HCC and 30 normal tissues as control group. HSP70, GPC3 and GS were expressed in higher levels in HBV-related HCC samples compared to HBV alone group. The results showed that the labeling index of HSP70, GPC3 and GS are correlated with immunohistochemical and molecular expressions of HSP70, GPC3 and GS. The sensitivity and specificity for HCC diagnosis were 43.4% and 89.7% for HSP70, 64.3% and 90.4% for GPC3, and 60.7% and 94.3% for GS, respectively. The sensitivity and specificity of the panels with 3, 2 and 1 positive markers, regardless of which one, were 21.6% and 100%, 51.3% and 100% and 93.4% and 80.5% respectively. The current study demonstrated an association between HSP70, GPC3 and GS expressions and HBV-related HCC in our population. It was concluded that HSP70, GPC3 and GS expressions could be useful biomarkers for increasing the specificity and sensitivity of HCC diagnosis to acceptable level. Also, proper combinations of these 3 markers could improve diagnostic accuracy.

Background Inosine triphosphate pyrophosphatase (ITPA) gene single nucleotide polymorphisms (SNPs), rs1127354 and rs7270101, may cause a functional impairment in ITPase enzyme, resulting anemia protection in patients with chronic hepatitis C virus (HCV) infection undergoing ribavirin (RBV)-dependent regimens. The main purpose of this study was to provide and validate a simple, rapid, and inexpensive polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique for genotyping of ITPA rs1127354 and rs7270101 polymorphisms in chronic HCV-infected patients. Methods In the current study, 100 Iranian patients with chronic hepatitis C were examined and genotyped for ITPA rs1127354 and rs7270101 gene polymorphisms. To genotype rs1127354 and rs7270101 polymorphisms, PCR-RFLP technique and sequencing technique were performed on these samples. To validate the PCR-RFLP method, the PCR-RFLP genotyping results should be 100% concordant with the PCR-sequencing results. Results The rs1127354 and rs7270101 polymorphisms of ITPA gene were genotyped by PCR-RFLP technique and sequencing simultaneously, and the results of both techniques were 100% concordant in all 100 patients. Both PCR-RFLP and sequencing techniques indicated that the genotypic frequency of rs7270101 was 80% AA, 19% AC and 1% CC, and for rs1127354 was 79% CC, 20% CA and 1% AA, respectively. Conclusion We developed and validated a rapid and inexpensive PCR-RFLP technique for the detection of ITPA rs1127354 and rs7270101 gene polymorphisms.

Background Evaluation of trends in the rate of transfusion-transmitted infections (TTIs) in blood donors is essential for monitoring blood supply safety and donor screening effectiveness. The aim of this study was to determine the trends and prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis seromarkers among blood donors referred to Tehran Blood Transfusion Center (TBTC) from 2008 to 2013. Materials and methods The data of all blood donors referred to TBTC between 2008 and 2013 were collected. The prevalence of HBV, HCV, HIV, and syphilis infections were expressed by donation year and donors' characteristics (age, gender, educational level and donor status). Results Among 1,796,090 individuals who donated blood at TBTC from 2008 to 2013, analysis of trend for the prevalence of HBV showed a significant decrease from 423 to 153 per 10 5 donors. The similar pattern of decrease was observed for the prevalence of HCV from 139 to 69 per 10 5 donors, however the rate of decrease in HCV prevalence was slower than the rate of decrease in HBV prevalence. The prevalence of HIV was constant while the prevalence of syphilis showed a sharp decrease in 2009 and a constant prevalence from 2010 to 2013. The top three parameters influenced the rate of TTIs were donor status, age, and educational level. Conclusion The decreasing prevalence and trends of TTIs among the studied donors demonstrated that the safety measures which were employed in recent years in Iranian Blood Transfusion Organization have been effective.

Hepatitis B envelope antigen (HBeAg)-negative hepatitis B virus (HBV) infection exerts both inactive carrier (IC) state and chronic hepatitis B (CHB), which are sometimes difficult to be differentiated. We aimed to assess the role of hepatitis B surface antigen (HBsAg) level in differentiation of CHB and IC among a group of chronic HBeAg-negative HBV-infected patients. A total of 251 HBeAg-negative HBV-infected patients were enrolled. Serum HBV DNA and HBsAg levels were determined for each patient. HBV DNA quantification with cutoff value 2000IU/mL for diagnosis of CHB had 99.0% sensitivity and 74.1% specificity. A cutoff value of HBsAg level at 1000IU/mL was more reliable for diagnosis of CHB with 82.7% sensitivity and 66.2% specificity than other HBsAg cutoff values. There was a positive correlation between HBV DNA and HBsAg levels in both CHB (r=0.42, P

Objectives: Health care workers, including dentists, are at the front line for acquiring blood-borne virus infections. This study aimed to investigate the prevalence of hepatitis B, hepatitis C and human immunodeficiency viruses among Iranian dentists. Material and Methods: The survey included 1628 dental health care workers who attended the 51st annual Congress of the Iranian Dental Association. Data on the risk of blood-borne virus transmission during health care and infection control practices were gathered from self-administered questionnaires. Sera were screened serologically by enzyme-linked immunosorbent assay (ELISA). The positive samples were examined by polymerase chain reaction (PRC) followed by direct sequencing. Results: Six (0.36%) and 81 (5.0%) were positive for hepatitis B surface antigen (HBsAg) and (anti-hepatitis B virus core antigen (anti-HBc), respectively. Only 1 (0.061%) was positive for anti-hepatitis C virus (anti-HCV). No case was positive for anti-human immunodeficiency virus (anti-HIV). One case was diagnosed as being occult hepatitis B virus (HBV) infection. One thousand five hundred thirty-five (94.3%) of participants had received at least 1 dose of HBV vaccine. One thousand three hundred fifty-nine (88.5%) contained hepatitis B surface antibody (anti-HBs) > 10 IU/ml, of whom 55 (4.0%) were anti-HBc positive, suggesting that they had been infected with HBV in the past. Anti-HBc positive cases had past histories of hepatitis, either their own or their spouses’. Individuals with inadequate anti-HBs levels (< 10 IU/ml) were significantly more prevalent among anti-HBc positive cases (p < 0.001). Conclusions: The prevalence of blood-borne viruses among dental HCWs found in this study was lower than past reports from Iranian dentists and general population. The implementation of HBV vaccination together with improvement in infection control procedures has reduced the potential for risk infection among Iranian dentists.

Background Hepatitis B virus (HBV) infection is a worldwide health issue and is well known for being the main cause of developing secondary liver complications such as cirrhosis and hepatocellular carcinoma (HCC). The PNPLA3 rs738409 polymorphism has been investigated conclusively with occurrence risk of steatosis and cirrhosis. Therefore, performing a meta-analysis of the available studies with the aim of clarifying the association between rs738409 and occurrence risk of steatosis and cirrhosis among HBV-infected patients would be helpful. Methods Chronic HBV infection was defined as the persistence of HBsAg for more than 6 months. To gather sufficient data for this meta-analysis, reliable databases were conclusively searched using appropriate keywords. Only studies that satisfied the inclusion criteria were enrolled in the present study. Results This meta-analysis pooled four studies with 1135 cases of chronic hepatitis B (CHB) to evaluate the impact of PNPLA3 SNP on liver steatosis and also pooled five studies with 3713 cases of CHB to evaluate the impact of PNPLA3 SNP on cirrhosis. The association of rs738409 with each complication was investigated. The rs738409 was found to be associated with steatosis in recessive [p = 4.57 × 10-6 , odds ratio (OR) = 2.85], dominant (p = 4.35 × 10-6 , OR = 1.84), co-dominant (p = 6.18 × 10-8 ; OR = 3.74) and allelic (p = 9.79 × 10-9 ; OR = 1.78) models. No association was found between rs738409 and cirrhosis development in recessive (p = 0.99, OR = 1.00), dominant (p = 0.30, OR = 0.92), co-dominant (p = 0.74; OR = 0.96) and allelic (p = 0.45; OR = 0.96) models. Conclusions Although the PNPLA3 rs738409 G allele has been associated with the risk of steatosis in CHB patients, no association between this polymorphism and the risk of cirrhosis was seen.

Objectives Different studies have been conducted on the role of curcumin in health since having multiple properties, including antioxidant and anti-inflammatory effects. Due to the lack of studies regarding curcumin effects on obese patients with non-alcoholic fatty liver disease (NAFLD), our protocol was designed to assess nanocurcumin impacts on blood sugar, lipids, inflammatory indices, insulin resistance and liver function, especially by nesfatin. Setting This trial will be conducted in the Oil Company central hospital of Tehran, Iran with a primary level of care. Participants 84 obese patients with NAFLD diagnosed using ultrasonography will be employed according to the eligibility criteria‎. Interventions The patients will be randomly divided into two equal groups (nanocurcumin and placebo, two 40 mg capsules per day with meals for 3 months, follow-up monthly). Also, lifestyle changes (low-calorie diet and physical activity) will be advised. Measures of the primary and secondary outcomes A general questionnaire, 24 hours food recall (at the beginning, middle and end) and short-form International Physical Activity Questionnaire will be completed. Blood pressure, anthropometrics, serum sugar indices (fasting blood sugar and insulin, insulin resistance and sensitivity and glycosylated haemoglobin), lipids (triglyceride, total cholesterol and low-density and high-density lipoprotein-cholesterol, inflammatory profiles (interleukin-6, high-sensitivity C-reactive protein, and tumour necrosis factor-alpha), liver function (alanine and aspartate transaminase) and nesfatin will be measured at the beginning and end of the study. Conclusion This trial would be the first experiment to determine nanocurcumin efficacy on certain blood factors among obese patients with NAFLD. Nevertheless, studying the potential consequences of curcumin in various diseases, especially NAFLD, is required for clinical use. Trial registration number IRCT2016071915536N3; pre-results.

Context Hepatitis E virus (HEV) as a hepatotropic virus is one of the major global health concerns. Autochthonous HEV transmitted by oral fecal-route in poor sanitation conditions as well as vertical and rarely blood transfusion. HEV occurrence is more common in developing countries and recently increased in developed countries too. Middle East (ME) and Eastern Mediterranean region (EMR) of WHO have been an endemic region for HEV infection. In this regard, we aimed to design a systematic review and pooled analysis to determine seroprevalence of anti-HEV antibody in ME and EMR countries. Evidence acquisition By using PRISMA guideline, data were collected from papers identified through PubMed, Web of Science, Science Direct, Scopus and also from some national and regional databases from January 1990 to June 2016. Serum anti-HEV antibody (IgG) used for HEV prevalence estimation. HEV prevalence in the ME, WHO EMR countries, and in total, calculated by each country population size based on 2015 UN report. Results overall, 62 papers with a total sample size of 31,673 were fulfilled our eligibility criteria and included in our project. Considering anti-HEV antibody (IgG), prevalence of HEV infection in the countries of ME, WHO EMR and in total were 12.17% (95% CI: 11.79–12.57), 11.81% (95% CI: 11.43–12.21), and 11.87% (95% CI: 11.52–12.23) respectively. Conclusions HEV seroprevalence in WHO EMR and ME countries has high rate and more considerations are needed for the prevention and control of this infection especially in high-risk groups such as pregnant women.

Background The World Health Organization seeks to achieve the goal of viral hepatitis elimination by 2030 and lack of general knowledge about viral hepatitis seems to be a barrier to reaching this goal. This study was designed to evaluate the knowledge, attitude, and practice (KAP) regarding hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among Iranian health sciences students in 12 Iranian medical sciences universities using a national survey. Methods This survey was conducted during the second Hepatitis Awareness Campaign, which was held during the Iranian National Hepatitis Week (October 22-28, 2016). Students who visited our booths and were willing to participate in our survey were selected using convenience sampling and their HBV- and HCV-related KAP were evaluated. Results Two thousand one hundred fifty-six health sciences students with mean age of 21.24 years participated in our survey. The mean KAP scores were 7.35 (out of 10), 4.88 (possible score, –20 to +20), and 5.67 (out of 9). Students with experience of accidental exposures to blood (21.6%) had better KAP scores compared with the students without such experiences. The mean KAP scores were associated with subjects' year of education, field of study, university, and province (P Conclusions Our study showed that HBV- and HCV-related KAP in a sample of Iranian health sciences students was not satisfying. The results also demonstrated priority of needing intervention regarding KAP in some subject areas, lower years of education, and some universities compared with others.