Evaluation of autoimmune liver disease natural history in patients referred to Middle East Liver Diseases (MELD) center.

BACKGROUND: Autoimmune liver diseases (AILD) are increasing and common forms of chronic liver disease (CLD) with different clinical responses and characteristics which can result in cirrhosis. This study aimed to investigate the natural history and characteristics of AILD in an Iranian population. METHODS: Patients with AILD [Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and Overlap Syndrome (OS)] referred to Middle East Liver Diseases (MELD) center, Tehran, Iran, between January 2002 and December 2022 were included in this retrospective cohort study. The main features of natural history (the trends of liver functional tests (LFT), Auto-Antibodies, response to treatment and cirrhotic status) along with demographic data were studied. RESULTS: Two hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC, 48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were included. Baseline laboratory tests revealed that patients with AIH exhibit elevated transaminase levels. However, patients suffering from PBC and PSC displayed increased alkaline phosphatase levels. Conversely, in overlap syndrome patients, both transaminases and alkaline phosphatase were observed at high levels. Autoantibodies represented themselves as important diagnostic markers for the AIH and PBC but not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with AIH and overlap syndrome respectively and 21 patients 11 (6.9%) of AIH and 10 (20.8%) of overlap syndrome) were non-responders. Other patients in these two categories were considered as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis regression was observed in some AIH and PBC patients. CONCLUSION: Appropriate medication management for AILD patients may leads to regression from cirrhosis and improvement of manifestations; while discontinuation of medication may cause relapses. However, patient suffering from PSC showed limited response to treatment.

Effect of a moderately carbohydrate-restricted diet on liver enzymes, steatosis and fibrosis in normal-weight individuals with non-alcoholic fatty liver disease: study protocol for a parallel randomised controlled clinical trial.

INTRODUCTION: Non-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 ANALYSIS: This 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 DISSEMINATION: The 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 NUMBER: IRCT20210119050086N1.

The CD8+ T cell exhaustion mechanisms in chronic hepatitis B infection and immunotherapeutic strategies: a systematic review.

INTRODUCTION: The hepatitis B virus (HBV) continues to be a leading cause of morbidity and mortality worldwide. In developing countries, HBV is the most common etiology of those liver diseases such as chronic hepatitis B (CHB), acute hepatitis B (AHB), acute-on-chronic liver failure (ACLF), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). CD8+ T cell exhaustion is a condition of T cell malfunction and reduction that plays a crucial role in the progression of HBV infection. AREAS COVERED: This systematic review attempts to evaluate the main inhibitory mechanisms involved in CD8+ T cell exhaustion, in different clinical phases of HBV infection and relation to disease progression. A systematic search in PubMed, Web of Science, and Scopus was performed to identify articles published in English till October 2022. EXPERT OPINION: According to the numerous conducted studies, we conclude that CD8+ T cell exhaustion commonly occurs in the tumoral and chronic suppressive environment and CHB and HCC patients; furthermore, this phenomenon is less seen in AHB and ACLF patients. The emergence of surficial inhibitory receptors (IRs) on CD8+ T cells is the leading cause of exhaustion, and programmed cell death protein-1 (PD-1) has much importance among the others.

A New Combination: Anti Glypican-3 scFv and Diphtheria Toxin with the Best Flexible Linker.

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)1-3YP7). In-silico and experimental investigation were performed to find out how many repeats of linker between toxin and scFv moieties are sufficient. Results of in-silico investigations revealed that the difference in the number of linkers does not have a significant effect on the main structures of the immunotoxin; however, the three-dimensional structure of two repeats of linker had a more appropriate structure compared to others with one and three linker replications. In addition, with enhancing the number of linkers, the probability of protein solubility has increased. Generally, the bioinformatics results of DT389-(GGGGS)2-YP7 structure showed that expression and folding is suitable; and YP7 scFv has appropriate orientation to bind GPC3. The experimental investigations indicated that the fusion protein was expressed as near to 50% soluble. Due to the high binding affinity of YP7 scFv and the proven potency of diphtheria in inhibiting protein synthesis, the proposed DT389-(GGGGS)2-YP7 immunotoxin is expected to function well in inhibiting HCC.

Wheat germ improves hepatic steatosis, hepatic enzymes, and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized, placebo-controlled, double-blind clinical trial.

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.

Economic evaluation of pan-genotypic generic direct-acting antiviral regimens for treatment of chronic hepatitis C in Iran: a cost-effectiveness study.

INTRODUCTION: Low-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. METHODS: A 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%. RESULTS: Among 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. CONCLUSION: Initiating 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.

Association of single nucleotide polymorphisms in immune-related genes with spontaneous HBsAg seroconversion: A systematic review and meta-analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Digital Marketing: A Unique Multidisciplinary Approach towards the Elimination of Viral Hepatitis.

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.

The effect of daily consumption of probiotic yogurt on liver enzymes, steatosis and fibrosis in patients with nonalcoholic fatty liver disease (NAFLD): study protocol for a randomized clinical trial.

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.

An on-site community-based model for hepatitis C screening, diagnosis, and treatment among people who inject drugs in Kerman, Iran: The Rostam study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

DT389-YP7, a Recombinant Immunotoxin against Glypican-3 That Inhibits Hepatocellular Cancer Cells: An In Vitro Study.

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.

Prevalence of Hepatitis B and Hepatitis C Infections among Incarcerated Individuals in Iran: A Cross-Sectional National Bio-behavioral Study in 2019.

Introduction: To realize the global goals of eliminating hepatitis B virus (HBV) and hepatitis C virus (HCV) by 2030, it is necessary to monitor the status of disease among target populations and undertake the required interventions. This study is the third round of surveys to determine the prevalence of hepatitis B and C infections among incarcerated individuals in different provinces of Iran. Methods: This study was conducted in five provinces of Iran (including Kurdistan, Ardabil, West Azerbaijan, Markazi, and Semnan) in 2019. The subjects of the study were selected from incarcerated people in prisons of all provinces that had not been studied in the previous two rounds of the surveys (in 2015 and 2016) in Iran. In this study, 15 prisons were selected and 2475 incarcerated individuals were enrolled into the study based on the multistage sampling method; the selected subjects were surveyed and their dried blood spot (DBS) samples were collected to test HBsAg and HCV-Ab. In cases with a reactive result for HCV-Ab, an HCV-RNA test was also performed on their serum samples. The relationships between independent variables and outcomes were evaluated via logistic regression. Results: Of all participants (2475 subjects) enrolled in the study, 54.18% were selected from northern provinces and 45.82% from the central provinces. The prevalence of HCV-Ab and HBsAg among incarcerated individuals was 5.66% (95% CI: 4.81% to 6.64%) and 2.42% (95% CI: 1.89% to 3.11%), respectively. Among HCV-seropositive individuals, 73.68% (95% CI: 64.70% to 81.01%) had current HCV infection (detectable HCV-RNA). The results showed that histories of imprisonment, drug use, unprotected sexual contact, drug injection, tattooing, and younger age in the first-time drug use in incarcerated individuals significantly increased the risk of HCV transmission. Among these behaviors, drug injection was more likely than other behaviors to result in contracting HCV in incarcerated individuals (OR: 22.91; 95% CI: 14.92-35.18; p < 0.001). Conclusion: To achieve international and national strategies targeted to eliminate HCV and HBV by 2030, it is necessary to pay special attention to prisons in Iran. It is recommended to continue HBV vaccination of eligible people in prisons. Developing screening and treatment protocols for individuals with HCV infection in prisons can help the country to achieve HCV elimination goals.

Treatment of hepatitis C virus infection with direct-acting antiviral agent-based regimens in Iranian patients with hereditary bleeding disorders.

BACKGROUND: Chronic hepatitis C (CHC) is one of the most important comorbidities in patients with hereditary bleeding disorders (HBD). The present study aimed at evaluating the effectiveness of direct-acting antiviral agent (DAA)-based interferon-free HCV antiviral regimens in patients with HBD. PATIENTS AND METHODS: The present study was performed on the patients with HBD and CHC between 2015 and 2019. Sofosbuvir-based interferon-free regimens with or without ribavirin were prescribed to treat HCV infection. The main endpoint of the study was to determine the sustained virologic response (SVR), assessed 12 weeks after the completion of treatment. RESULTS: A total of 147 patients with a mean age of 41.1 years were enrolled in the study; 4.1% of them were co-infected with HIV, 25.2% had cirrhosis, and 76.9% of them were diagnosed with hemophilia A. HCV genotype-1 includes the largest number (68.1%) of patients. 46.3% of patients were treatment-naïve and others had a treatment history with interferon-based regimens. Out of 147 patients, 15 patients were lost to follow-up during treatment or for SVR evaluation or discontinued treatment. 132 subjects completed treatment and were evaluated for SVR, 12 weeks after the completion of treatment. All of the patients achieved SVR 12 (SVR rate: 100%, 95% CI 97.2-100%). CONCLUSION: Hepatitis C DAA-based regimens are the effective treatments for CHC in patients with HBD, regardless of the treatment modifiers such as previous treatment experience, cirrhosis, HIV co-infection, and HCV genotype.

Immunotoxins Immunotherapy against Hepatocellular Carcinoma: A Promising Prospect.

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.

Harm reduction program and hepatitis C prevalence in people who inject drugs (PWID) in Iran: an updated systematic review and cumulative meta-analysis.

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.

Seroepidemiology of hepatitis E virus infection in patients undergoing maintenance hemodialysis: Systematic review and meta-analysis.

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.

The efficacy of flaxseed and hesperidin on non-alcoholic fatty liver disease: an open-labeled randomized controlled trial.

BACKGROUND/OBJECTIVES: 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. SUBJECTS/METHODS: 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. RESULTS: 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 < 0.008). CONCLUSIONS: In conclusion, our study confirmed that hesperidin and flaxseed supplementation improved glucose and lipid metabolism, while reduced inflammation and hepatic steatosis (controlled attenuation parameter) in NAFLD patients. The synergistic effects of their combination were observed on plasma glucose concentration and HOMA-IR.

Therapeutic effects of Chlorella vulgaris on carbon tetrachloride induced liver fibrosis by targeting Hippo signaling pathway and AMPK/FOXO1 axis.

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.

Eradication of hepatitis C virus infection in thalassemia patients in Iran using various treatment strategies.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is considered as one of the leading causes of liver disease in thalassemic patients in Iran. Over 40% of the mortality in these patients is related to HCV. OBJECTIVES: The present study aimed at estimating HCV prevalence in thalassemic patients in Iran and to determine the number of infections until eradication is achieved. METHODS: A meta-analysis approach was used to estimate the number of HCV-infected thalassemic patients in the country. The prevalence rate was measured using a modeling approach to predict the number of cases until eradication using several scenarios in terms of testing and treatment, in particular the use of direct acting antiviral drugs (DAAs). RESULTS: With the advent of DAAs with a high rate of treatment success, HCV could be eradicated earlier than originally thought among this group of patients. Based on previous predictions the number of HCV-infected thalassemic patients would have been below 66 by 2020. However, according to our predictions, the number will be less than 10 when using DAAs. CONCLUSION: We believe that HCV eradication can be achieved in thalassemic patients with an increased life expectancy by funding DAA-based new treatment strategies. This has been exemplified in Alborz, Lorestan, and South Khorasan provinces with HCV eradication in this group of patients.

Continuum of hepatitis C care cascade in prison and following release in the direct-acting antivirals era.

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.