Hepatitis Monthly
Volume:17 Issue: 5, May 2017

Hepatitis B virus (HBV) infection is a significant global problem. The main therapies for chronic hepatitis B are nucleos(t)ide analogues (NAs) and (pegylated) interferon (IFN). However, the prognosis of chronic hepatitis B is still not so optimistic since the low serological conversion rate and the high recurrence rate after drug withdrawal.
This aim was to evaluate the killing activity of cytotoxic T lymphocytes (CTLs) induced by dendritic cells transduced recombinant adenovirus associated virus (rAAV) with different hepatitis B virus gene fragment (HBV-S, C, E, X).
Peripheral blood mononuclear cells (PBMCs) were extracted from chronic hepatitis B patients , and the adhered cells were harvested to cultivate with recombinant adeno-associated virus with different hepatitis B virus (HBV) antigen gene fragment (rAAV-HBV-S, C, E, X) for 7 days by adding GM-CSF, IL-4 and TNF-α to generate mature dendritic cells (DCs). The DCs’ state were observed and their differentiation antigen molecules (CD) were detected by flow cytometry (FACS) to evaluate their maturation and function. DCs were co-cultured with prepared T lymphocytes to induce cytotoxic T lymphocytes (CTLs). The activity of CTLs induced by different DCs were compared by detection of lymphocyte CD molecules and cytokine levels. HepaG2.2.15 cells were target cells and HepaG2 cells as control. The specific killing activity of CTLs were compared by cell killing assay using 3-(4, 5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium (MTS).
The expression of phenotype CD14, CD80, CD83, CD86 from DCs transduced with rAAV-HBV-S, C, E, X and the secretion of cytokine IL-10, IL-12 were compared, respectively. CD80 in rAAV-HBV-S was the highest (P 0.05). The response of cytotoxic T-lymphocytes induced by different adeno-associated virus (AAV) vector delivery into dendritic cells had significant differences. In comparing the four antigens in terms of CD4࠽맹 cells, it was found that rAAV HBV-E group was the highest, and rAAV HBV-X group was the lowest (P 0.05).
These data suggest that rAAV-HBV-S, C, E, X delivery into DC may be all useful for immunotherapeutic strategies against hepatitis B virus infection and that the HBV X antigen gene may be the most useful.

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.
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.
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.
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).
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.

Nonalcoholic fatty liver (NAFLD) is a worldwide, leading cause of chronic liver disease, not yet approved medical treatment standards. The aim is to assess the effects of aerobic exercise sand calorie-restricted (CR) diet on many clinical and laboratory findings in patients with Nonalcoholic Steatohepatatis (NASH).
In Randomized controlled trial study, in Mashhad, between February 2010 - August 2011, Twenty-five patients with NASH, in ranging ages of 18 - 55, were randomly selected to be divided in to two groups, who received CR-diet and aerobic exercise (n = 12) and CR-diet alone (n = 13). We measured Anthropometric indices, cardio-respiratory fitness, and biochemical profiles in three steps, in baseline, and after 8 - 12 weeks of intervention. We measured hepatic steatosis and patient’s quality of life by ultra-sonography and short form (questionnaire) 36 in three steps. Data was then analyzed by paired and independent samples T Test.
We observed a significant improvement in BP, FBS, TG, HOMA-IR, ultra-sonography grading of steatosis and quality of life, only in patients who received aerobic exercises. (P value 0.021, 0.005, 0.006, 0.042, 0.010 and 0.012). Waist circumference, waist-to-height ratio, serum ALT and peak oxygen consumption improved in both groups; however, improvement was significantly, higher in patients who received aerobic exercises (P value 0.027, 0.011, 0.020 and 0.020). Body weight, BMI, body fat percentage and AST improved in both groups but they were not significantly different. No significant changes noted in total cholesterol, LDL and HDL in groups.
Add of aerobic exercises to CR diets can, not only enhance the therapeutic effects of calorie-restricted diet, but also bring more benefits in patients with NASH.

Therapy for chronic hepatitis C is based on direct-acting antiviral drugs (DAA) that include protease inhibitors, polymerase inhibitors, as well as inhibitors of NS5A protein. Resistance-associated substitutions (RAS) can be associated with inadequate treatment outcomes with DAA. People with HCV subtype 1a infection carrying Q80K polymorphism could have a reduced treatment response to a protease inhibitor simeprevir. The data on the prevalence of Q80K polymorphism and other RAS worldwide are quite variable.
The study goal was to analyze the frequency of Q80K polymorphism and other substitutions associated with HCV resistance to NS3 inhibitors in patients previously not treated with simeprevir infected with HCV subtype 1a from Croatia.
The study included 136 people with chronic hepatitis C and infected with HCV subtype 1a receiving clinical care at the department of viral hepatitis of the University hospital for infectious diseases, Zagreb and Croatian reference center for viral hepatitis from July 2015 to April 2016. All participants were not previously treated with simeprevir and not co-infected with HIV. Detection of Q80K polymorphism and other substitutions associated with resistance to NS3 inhibitors was performed by population-based sequencing on ABI PRISM® 3100 genetic analyzer. Phylogenetic tree was constructed using the Maximum Likelihood method and supported with a bootstrap test of 1000 replicates. Geno2Pheno algorithm was used for the interpretation of sequences, detection of resistance associated substitutions and determination of the clade of the sequence.
The prevalence of Q80K polymorphism was observed in 42.6% of patients while resistance to simeprevir (mediated by other RAS as well) was detected in 46.3% of patients. Phylogenetic analysis of subtype 1a sequences showed the separation into 2 clades and Q80K polymorphism was exclusively present in clade I isolates. Other RAS detected in the patients included V36L, T54S, V55A, S122R, and I170T.
In conclusion, the prevalence of Q80K polymorphism was found to be rather high in patients with chronic hepatitis C infected with clade I subtype 1a while other substitutions associated with resistance to protease inhibitors were rarely found in Croatian cohort. The results of this study confirm the need for pre-treatment screening for Q80K in subtype 1a patients considered for simeprevir treatment.

Spontaneous viral clearance occurs in 10% to 40% of individuals after hepatitis C virus infection. Some polymorphisms in IL-28B gene may influence the outcome of HCV infection. The present study aimed at investigating the genotype and allele frequency of IL-28B rs12979860 and rs8099917 SNPs in HCV infected patients in addition to determining their association with disease outcome.
A total of 302 patients with chronic hepatic C infection and 36 individuals whose infection was spontaneously cleared were included in this case-control study. The presences of chronic or spontaneously cleared infection in participants were determined by serologic and molecular methods. Genomic DNA of the participants was extracted using salting out method. IL-28B/IFN-λ3 gene polymorphisms were conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
The frequency of CC genotype (P = 0.001) and C allele (P = 0.0007) of IL-28B gene at rs12979860 SNP was significantly higher in participants with spontaneously cleared HCV infection compared to that of those who were chronically infected. In the case of rs8099917 SNP of IL-28B, no correlation was found between frequency of genotype (P = 0.17) or allele (P = 0.12) and HCV infection outcome. The results of haplotype analysis showed the association of CT (P = 0.012) and TT (P = 0.013) haplotypes with spontaneous clearance and chronic infection, respectively.
The findings implied that individuals with CC or CT genotype at rs12979860 SNP but rs8099917 SNP was not in association with spontaneous clearance of HCV in an Iranian population with HCV infection.

New treatment and vaccination strategies provide the opportunity for eliminating viral hepatitis. Lack of adequate knowledge seems to be a barrier against hepatitis elimination due to the emergence of newly infected cases.
The aim of this study was to evaluate the knowledge of Iranian (bio)medical students regarding hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and to determine the effect of hepatitis public awareness campaign (PAC), held by the students, on their knowledge level.
This prospective study was conducted during PAC by Iran Hepatitis Network for World Hepatitis Day in 2016. The PAC had 2 major parts: 1) training of the registered (bio)medical students in a workshop; and 2) sending the trained students to Tehran metro stations to promote public hepatitis awareness on July 26 - 28, 2016. Hepatitis knowledge of the students was evaluated by a validated questionnaire before the workshop, after the workshop, and after the end of PAC.
A total of 91 undergraduate students participated in the workshop, PAC, and the survey. The mean total knowledge scores of the students before and after the workshop were 56.2 ± 18.0 and 75.8 ± 17.9, respectively. Moreover, the scores further increased to 96.6 ± 6.1 after the end of the campaign (P The results demonstrated that knowledge regarding HBV and HCV infections is not sufficient in the study population. Therefore, we suggest using social activities and awareness campaigns to increase awareness among (bio)medical students.