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Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC). The exact molecular contributors to the development of HBV-related HCC are not yet completely understood. Recent studies demonstrated that the deregulation of the Wnt pathway is highly associated with the development of HCC. Besides, HBV is known to have roles in the deregulation of this pathway. The present study evaluated the molecular aspects of the Wnt pathway in HBV-related HCC in liver tissue samples. Viral characterization was done by identifying the HBx mutations and the assessment of intrahepatic viral load. The expression of Wnt pathway genes was assessed using real-time PCR and methylation-specific PCR. The intrahepatic viral load was significantly higher in tumor samples than in normal tissues (P = 0.0008). Aberrant expression was observed in Wnt-1, Wnt-7a, FZD2, FZD7, β-catenin, URG7, c-Myc, SFRP5, and GSK3β, among which Wnt1, FZD2, SFRP5, Gsk3β, and URG7 were associated with HBV. HBx mutations at positions I88, L116, and I127 + F132 were associated with the decreased expression of GSK3β and overexpression of URG7 and Wnt1. Alterations in the expression level of β-catenin, as well as some mutants of HBx, were correlated with the level of c-Myc. HBV-related HCC seems to be mostly coordinated with epigenetic behaviors of HBx, such a multi-functional peptide with suppressing/trans-activating functions.

Background: Infection with Hepatitis B virus (HBV) is still a leading cause of cirrhosis and hepatocellular carcinoma around the world. Objectives: Having recently received reports of high HBV prevalence in the South Khorasan Province in the Esfandiar village, we aimed to evaluate the prevalence of HBV in this region in comparison to neighboring villages, with associations to risk factors. Methods: This was a cross sectional study that included the Esfandiar village and neighboring villages, Marghoub, and Zenowghan. All of the Esfandiar and certain neighboring villages were summoned and blood sampling was performed along with the completion of a questionnaire. Positivity for HBsAg, anti-HBc along with the seromarkers of HCV and HDV were assayed using ELISA method. Statistical analysis was performed using the SPSS software with chi-square tests, logistic regression, and risk-estimation analysis. Results: From total 1.245 participants, 856, 172, and 217 cases were from the Esfandiar, Marghoub, and Zenowghan villages, respectively. The prevalence of anti-HBc in the Esfandiar, Marghoub, and Zenowghan were 48.7%, 20.3%, and 7.8%, respectively (P-value: 0.001). The figures for HBsAg were 17.8 %, 1.7 %, and 0.5 %, respectively (P-value: 0.001). HBV was more prevalent among those with a history of experimental dentistry, traditional phlebotomy, war veterans, endoscopy, and familial history of HBV. In Esfandiar, prevalence of HBsAg among below and above 22 years- old (beginig of natoinal HB vaccination) were 2.3% and 22.4%, respectively (P-value < 0.001). Conclusions: There was a very high prevalence of HBV in this small endemic region. The result showed the impressive effect of neonatal vaccination on reducing the incidence of hepatitis B, by 89.7%. Thus, the high prevalence requires an urgent consideration of organizing health programs and certain sociocultural behaviors.

Background: Hepatitis B virus (HBV) is the main infectious agent that causes liver disease and may lead to an acute or chronic HBV infection. Evidence from many studies have determined that host genetic factors play a significant role in determining immunization, clinical course, and recovery from HBV infection. A 32-bp deletion in the region of CCR5 gene (CCR5 ∆32) is one of the mutations that is known to provide genetic protection against chronic HBV infections. Objectives: In this study, the researchers aimed at assessing the protective effect of CCR5 ∆32 in subjects, who had recovered from HBV infection, as well as subjects that developed chronic HBV infection, in Birjand, Iran. Methods: The study consisted of 60 patients with chronic HBV infection (patient group) and 120 patients, who had previously recovered from HBV infection (control group). Genomic DNA was extracted from blood samples by the salting out method, and then samples were analyzed for the CCR5 ∆32 genotype utilizing the gap-polymerase chain reaction (Gap-PCR) technique. Variables were analyzed using the Chi-square test and P values less than 0.05 were considered as statistically significant. Results: The researchers found only one heterozygous CCR5 ∆32 mutation in the control group and absolutely no homozygous CCR5 Δ32 mutation in either the patient or control group. Conclusions: Because of no significant visible correlation between carrying the mutation and the possibility of recovery from HBV infection in the city of Birjand, it seems the protective effect of this mutation is absent in Birjand’s population.

Background It is estimated that about 5% of hepatitis B surface antigen (HBsAg) carriers are infected with hepatitis D virus (HDV) worldwide. Moreover, dual infection with hepatitis B virus (HBV) / HDV causes more severe diseases and leads to a higher risk of mortality.Objectives This study was performed to determine the prevalence of HDV infection and identify HDV-associated factors among HBsAg-positive patients in Birjand, South Khorasan province, Iran.Methods This descriptive, cross sectional study was conducted on 5235 participants in line with a previous study on the seroprevalence of HBV in South of Khorasan. HDV was assessed through evaluating the blood serum of diagnosed HBsAg-positive patients (85 cases) by ELISA test. For statistical analysis, descriptive statistics were calculated, using SPSS version 22.Results In this study, the mean age of HBsAg-positive patients was 45.1 ± 12.9 years (minimum, 22 years; maximum, 70 years). In total, 1 out of 85 cases was positive for HDV virus. The prevalence of HDV infection among HBsAg-positive patients was 1.2% (95% CI, - 1.2 to 3.5).Conclusions The low prevalence of HDV infection in South of Khorasan was remarkable, considering the great area of this province, use of a comprehensive and inclusive sampling strategy, and mutual borders with Afghanistan.

Background: Infection with the hepatitis B virus (HBV) is an important global health problem. Knowledge of the geographic dis- tribution pattern of HBV infection can help to control the spread of the disease. Objectives: To determine the prevalence of HBV infections and risk factors for the disease for the first time in Birjand, Southeastern Iran. Methods: This was an analytical cross-sectional study conducted in 2013 - 2014 of 5235 HBV cases in Birjand, South Khorasan Iran. Subjects aged 15 - 70 y were selected using the cluster sampling method. Blood samples were taken and tested at a reference labora- tory for the hepatitis B core antibody (anti-HBc). Seropositive specimens were tested for the hepatitis B surface antigen (HBsAg). Results: The mean age ( SD) was 39.07 ( 14.04) y, and 786 (15%) subjects were anti-HBc positive. The prevalence of HBsAg was 1.6% (n = 85). The prevalence of anti-HBc seropositivity was significantly higher in subjects with a lower level of education (P = 0.09), older subjects (P = 0.001), intravenous (IV) drug users (P

Context: Hepatitis C virus (HCV) infection is a major public health issue worldwide, including Iran. The new direct-acting antiviral agents (DAAs) with high efficacy have changed the landscape of HCV treatment. This guideline provides updated recommendations for clinical management of HCV infection in Iran. Evidence Acquisition: The recommendations of this guideline are based on international and national scientific evidences and consensus-based expert opinion. Scientific evidences were collected through a systematic review of studies that evaluated efficacy and safety of DAA regimens, using PubMed, Scopus and Web of Science. Expert opinion was based on the consensus of Iran Hepatitis Scientific Board (IHSB) in the 3rd national consensus on management of Hepatitis C in Iran, held on 22nd of July 2016. Results: Pegylated Interferon alpha (PegIFN), Ribavirin (RBV), Sofosbuvir (SOF), Ledipasvir (LDV) and Daclatasvir (DCV) are currently available in Iran. Pre-treatment assessments include HCV RNA level, HCV genotype and resistance testing, assessment of liver fibrosis, and underlying diseases. In HCV genotype 1 and 4, DCV/SOF and LDV/SOF are recommended. In HCV genotype 2, SOF plus RBV and in HCV genotype 3, DCV/SOF is recommended. Additional care for underlying diseases should be considered. Conclusions: Affordable new HCV treatment regimens are available in Iran, providing an opportunity for HCV elimination. Recommendations provided in this current national guideline can facilitate evidence-based management of HCV infection.

Background Hemophilic patients require long-life intravenous infusion of factor concentrates to treat bleedings. This could increase the risk of transmission of blood-borne infections like hepatitis C. Objectives The current study was aimed at investigating the immunity status against hepatitis A in hemophilic patients in south Khorasan and evaluating the necessity of hepatitis A vaccination for this population. Patients and Methods A cross-sectional descriptive study was conducted between 2014 and 2015 on all hemophilic patients of south Khorasan province, Iran (n = 108) for anti-HAV total, anti- HCV, HBs-Ag, anti-HIV, and anti-HTLV-I /II. Note that no one had already received a hepatitis A vaccine. Results As our results show, 77.8% of the participants (59% under 20 and 88.4% above 20 years old) were seropositive for anti-HAV total; 20.4% and 2.8% (three patients) of the cases were anti-HCV positive and anti-HTLV-1 positive, respectively, while none of the subjects were HBS-Ag or HIV-Ab positive. Seventeen of the patients (15.75%) showed a co-infection of HAV with HCV, and five HCV-infected patients (22.73%) had no immunity against hepatitis A. There was a significant relationship between age, rural life, and anti-HAV positive state in our patients (P < 0.001). No significant relationship between positive anti-HAV status and sex (P = 0.16), severity of hemophilia (P = 0.23), and infection with HIV, HCV, HTLV-1, and hepatitis B (P > 0.05) was detected. Conclusions More than 40% of the hemophilic patients under 20 years of age in the present study had no immunity against hepatitis A, and 23% of hepatitis C patients had not had a hepatitis A co-infection yet. Since hepatitis A can show a fulminant course in hepatitis C patients, vaccination against hepatitis A seems necessary in hemophilic patients in the region.

Background: Hepatitis delta virus (HDV) is a defective RNA virus dependent on Hepatitis B virus (HBV) infection for its replication and expression. All patients with HBV infection should be tested for the presence of HDV infection. It is estimated that approximately 5% of hepatitis B surface antigen (HbsAg) carriers in the world are HDV infected patients. HBV-HDV co-infection may lead to more severe acute disease and higher risks of fulminant hepatitis, cirrhosis, and hepatocellular carcinoma than those having HBV infection alone. Also, HBV infected patients with HDV super-infection have a higher rate of progression to chronic disease and serious complications. Objectives: Our aim was to determine the prevalence of HDV infection among chronic hepatitis B (CHB) patients attending Birjand Hepatitis Clinic, East of Iran. Materials and Methods: A cross-sectional analytical study was conducted on 413 CHB patients in 2012. Serology test for anti-HDV was measured by ELISA in these patients. CHB patients had positive hepatitis B surface antigen for at least 6 months before the study entrance. Results: The mean age of CHB patients was 38.5± 11.9 years and 55.9% of them (231 patients) were male. There were 13 cases (3.1%) with HDV infection. There was no association between positive anti-HDV serology and factors such as age, gender, carrier state, liver enzymes, and positive hepatitis B e antigen (HBeAg) serology. Conclusions: Although HDV had a low prevalence in our area, it is important for healthcare providers and policy makers to plan preventive strategies for HDV spread as well as HBV prevention programs among high risk population.

Background Immunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness. Objectives The aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments. Materials and Methods Hepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database. Results All strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively. Conclusions RT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option.

Background Nonalcoholic fatty liver disease (NAFLD) is one of the most common reasons of enzyme increase in liver. In About 10 percent of patients with NAFLD, the disease progresses toward Non Alcoholic Steatohepatitis (NASH) and about one third of them may progress toward cirrhosis, liver dysfunction, and even hepatocellular carcinoma. Objectives According to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease, the aim of this study was to assess the effects of metformin, pioglitazone, and silymarin on treatment of NAFLD. Patients and Methods Sixty six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo’ali Hospital, Qazvin, Iran, were assigned randomly into three groups (n = 22). First group was treated by pioglitazone 15 mg/d, second group by metformin 500 mg/d, and third group by silymarin 140 mg/d. All patients underwent clinical and biochemical evaluations including weight, fasting blood sugar (FBS), lipid profiles, body mass index (BMI), aspartate aminotransferase (AST ), alanine aminotransferase (ALT), and serum insulin levels in pre- and post-intervention after eight-week follow up. Results Before the treatment there was no significant difference between three groups with respect to average age, BMI and gender, FBS, lipid profile, AST, ALT, serum insulin level, and Homeostasis Model Assessment (HOMA) index for insulin resistance. After the intervention, a significant reduction was observed in average amount of FBS, lipid profile, ALT, AST, serum insulin level and HOMA index in three groups (P < 0.01). The most reduction in average FBS, TG, serum insulin level, and HOMA index was observed in pioglitazone group, the most reduction in average amount of cholesterol was seen in metformin group, and the most decrease in average amount of AST and ALT occurred in silymarin group. Conclusions These results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD. Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups.

Background and Aims Currently, vaccination is the most effective protective tool against hepatitis B virus infection. Some studies have shown that positive results for a hepatitis B virus surface antigen (HBsAg) test may be seen after vaccination. Materials and Methods In this clinical trial study, 62 healthy adult volunteers were randomly assigned to receive either the Engerix-B or the Hepavax-Gene hepatitis B recombinant vaccine. Blood samples were drawn 1, 3, and 5 days after vaccination and were tested for HBsAg using two different ELISA kits (Behring and Mega). Results HBsAg was positive in 5, 3, and 2 participants of the Engerix-B group in the 1st, 3rd, and 5th days after vaccination, respectively, using the Behring ELISA kit the test was positive in only one subject in the Hepavax-Gene group, on the 5th day after vaccination. No positive result was seen in any groups when the Mega ELISA kit was used to test the specimens. Conclusions Our results showed transient HBsAg antigenemia after vaccination against hepatitis B. This condition depends on the type of vaccine and the HBsAg diagnostic test.