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Introduction: Infection due to hepatitis B virus (HBV) could be due to wild or mutant viruses. The HBeAg negative chronic hepatitis B (HbeAg-CHB) is unable to produce hepatitis B, e antigen (HbeAg), so that patients with this varient do not present with HBV characterized by HbcAg in the serum. HbeAg-CHB usually proceeds to serious liver disease. The prevalence of different viral forms in patients with chronic liver disease in Iran has not been established.
Materials and Methods: Seventy-six Hamadanian patients with over 6 months HBSAg positivity were enrolled. Patients with co-infection of HIV, HCV, past history of alcoholism, fatty liver, using of hepatotoxic drugs, autoimmune hepatitis and other metabolic liver disease were excluded. All patients were screened for Hhe Ag. HbeAb. HBV DNA by PCR, AST, ALT, ALK. pH and bilirubin.
Results: Eleven (14.5%) patients had HheAg-CHB (HbsAg +ve, HbeAg-ve / ve/anti HbeAb + ve, HBV DNA + ve and elevated AST, ALT) and 6 (8%) had normal transminases (AST and ALT) accompanied by the remaining criteria of HbeAg-CHB. 59 patients (77.5%) were infected with wild type HBV, ie: HBSAg + ve, HbeAg-ve, HbeAb + ve, HBV DNA- ve, and normal AST, ALT.
Conclusion: Frequency of HbeAg.CHB in Hamadan is 14.5% knowing of this varient of chronic hepatitis B is important since the HbeAg-CHB have worse prognosis than wild type and more better response to lamivudine than interferon.

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Introduction: Hidden hepatitis B is a condition in which the surface antigen of hepatitis B in the patient's serum is negative but the DNA of the hepatitis B virus is detected in the serum or liver tissue. In this study, the prevalence of latent hepatitis B in chronic hepatitis C patients and their biochemical and histological changes were investigated.
method: In this descriptive study, target sampling was performed so that 27 chronic hepatitis C patients whose HBsAg was negative and during 2001 and 2002 to two hepatitis centers of Tehran and Research Center for Gastrointestinal and Liver Diseases of Shahid University of Medical Sciences Beheshti came in and underwent liver sampling. On the hepatic paraffinic block of these patients, polymerase chain reaction tests were performed for the presence of HBVDNA, as well as immunohistochemical tests for the presence and detection of HBsAg and central hepatitis B antigen.
Results: Of the 27 PCR samples examined, patients reported positive HBVDNA in 5 cases (19%). In all of these patients, IHC tests were reported to be negative for HBsAg and HBcAg. Histological changes of cirrhosis and irreversible cirrhosis symptoms were seen only in the HBVDNA group.
Conclusion: The prevalence of latent hepatitis B is relatively high in patients with hepatitis C. In these patients, latent hepatitis B can exacerbate liver damage and accelerate the progression of cirrhosis.

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Introduction: Hepatitis B is a disseminated liver inflammation from HBV, that causes diseases and a large number of deaths. Regarding the fact that some of the vaccinated people are non responder (NR), evaluation of immunity in vaccinated ones and identification of NR especially in high risk group is necessary.
Materials and Methods: In this descriptive study blood samples of all medical students of Borujerd Azad university at the age of 18-25 and vaccinated personnel of Borujerd Shariaty hospital were tested for Anti.HBS-Ab level by ELISA method with Radim kit (cat.KHB31). Results were analyzed according to the number of received vaccines, the duration of vaccination and demographic criteria using descriptive statistics.
Results: About 90% of samples had protective immunity and 10% were NR. 8% of immune group had more than 1000, 17.2 % between 500-1000 and 74.8 % between 10-500 miu/ml of Ab titer. About 75% of immune samples had received two vaccines. In NR group 53% had received three vaccines and 47% had two. 4% of samples were immune with the duration less than one month after vaccination which 85 % of them had two vaccines.
Conclusion: Herd immunity was 90% which is accordant to most studies. In some studies with different results the effective criteria were not differentiated. So regarding these differences, vaccinated people are recommended to evaluate their HBS.Ab level.

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Introduction: A high prevalence of HCV infection among hemodialysis patients has been reported worldwide. Risk factors such as history of blood transfusion, duration of hemodialysis and recently nosocomial transmission of HCV in hemodialysis units have been identified. In this study the prevalence of Hepatitis C virus antibody and risk factors in hemodialysis patients in Markazi province is investigated. Materials and Methods: In this cross-sectional analythical study, blood samples were obtained from all 204 hemodialysis patients. Samples were tested for anti-HCV antibodies by using third generation enzyme immunoassay. The reactive samples on ELISA were confirmed by the third generation RIBA. Risk factors were evaluated by a questionnaire. Data was analysed using Chi square and logistic regression. Results: The prevalence of anti-HCV antibody among hemodialysis patients was 4.9%.Duration of hemodialysis was identified as a major risk factor in transmission of HCV (p=0.004). There was a significant relationship between anti-HCV positivity and previous renal transplantation (p=0.032). Female sex was another risk factor for HCV infection (p=0.030). There was no significant relationship between anti-HCV positivity and history of blood transfusion. Conclusion: Nosocomial transmission of HCV within hemodialysis units seems to be a route of infection in patients on hemodialysis in Markazi province. Application of dialysis precautions recommended by CDC can reduce the prevalence of HCV infection among hemodialysis patients in this province.

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Background: TTV is the first human circoviridae that was isolated from Japanese patients with unknown hepatitis in 1997. Since then, several studies have been done on different aspects of TTV pathogenesis. The aim of this study is to determine the prevalence of TTV in patients with chronic hepatitis using two different primer sets. Materials and Methods: In this descriptive study, blood samples from 240 patients with chronic hepatitis C at Professor Alborzi Clinical Microbiology Research Center were assessed in terms of the presence of TTV DNA in plasma through the nested polymerase chain reaction using two primer sets. Results: Of the 240 patients, TTV-DNA was detected in 220 (92%) patients with chronic hepatitis C using 5΄-UTR primer and in 12 (5%) patients using N22 primer. According to the demographic data, there was not a significant difference between male female patients in prevalence of TTV infection. Conclusion: The prevalence of TTV DNA in plasma samples from patients with chronic HCV by using 5΄-UTR primer was high and it was congruent with studies done in other countries however, N22 primer showed a lower prevalence of viral DNA in the samples. Overall, there was not a significant correlation between sex and the presence of viral DNA in patients. Controversial or high prevalence of this virus in HCV infected people necessitate further studies for determining the relationship between HCV and TTV infection.

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Background: Low immunogenicity of hepatitis B vaccine is an important problem in patients with chronic renal failure (CRF). A possible solution is intradermal versus conventional intramuscular delivery of vaccine in this population. The goal of this study was to compare the efficacy of these routes of vaccination in Bu-alicina Dialysis Center, Qazvin, Iran. Materials and Methods: This randomized clinical trial was done on 29 CRF non-responders randomly allocated to two groups. Fifteen patients received 40 μg of euvax B vaccine intradermally and 14 patients received 160 μg of this vaccine intramuscularly. Anti-HBs antibody titre was measured after 1, 6, and 12 months. Seroprotection was defined as anti-HBs antibody titre above 10 lU/L. Data were analyzed using SPSS software version 16. Results: Difference of seroprotection rate between two groups was not statistically significant after1and 6 months however, after 12 months, seroprotection rate was 93.3% in the interadermal group versus 50% in the intramuscular group (p<0.05). Conclusion: Considering the high cost of vaccination, intradermal vaccination may be a reasonable choice in CRF patients.

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Background: Nucleos(t)ide analogues, such as lamivudine and adefovir, are effective drugs for treatment of hepatitis B patients. However, long-term treatment with these drugs leads to the emergence of the nucleos(t)ide analogue resistant strains. The impact of nucleos(t)ide analogues on the emergence of HBsAg escape mutations is not clarified. Hence, the aim of this study was to determine HBsAg escape mutations in chronic hepatitis B patients treated with nucleos(t)ide analogues. Materials and Methods:A cross-sectional study was performed on 50 patients with chronic hepatitis B under treatment with nucleos(t)ide analogues (lamivudine and/or adefovir) and 50 naive chronic hepatitis B patients. HBV DNA was extracted from plasma and S gene of virus was amplified by Nested-PCR followed by direct sequencing. HBsAg gene sequence of the samples was evaluated for detection of HBsAg escape mutations. Results: Among the 100 patients, the following HBsAg escape mutations were identified: sQ101H, sG119R, sP120S, sP127S, sA128V, sG130N, sG130R, sT131I, sM133I, and sY134N. The frequency of HBsAg escape mutations in patients under treatment of nucleos(t)ide analogues was 16% and in naïve patients was 6% (p=0.2, OR=2.98). Conclusion:According to the obtained results, there seems to be no association between using nucleos(t)ide analogues and emergence of HBsAg escape mutations.

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Background: Chronic hepatitis B virus (HBV) infection is a multi-factorial disease that is accompanied with serious clinical complications. Host’s genetic background, especially immune–genetic factors, is critical in the pathogenesis of infection. Gamma interferon ((INF-γ) and its receptor have an important role in immune response to the virus and clinical course of the disease. The aim of this study is to investigate the association between single nucleotide polymorphism -611G/A located in promoter of gamma interferon receptor1 gene (INFGR1) and chronic HBV infection. Materials and Methods: In this Case Control study, genomic DNA from peripheral blood samples of 150 chronically HBV infected patients and 150 healthy controls was extracted by phenol-chloroform method. DNA analysis was performed by PCR-RFLP method and P<0.05 was considered significant. Results: After stages of genotyping and statistical analysis, a significant difference was observed between patient and control group, so that genotype GG was higher in the control group compared to the patient group. Conclusion: The host’s immune-genetic background can play an important role in the pathogenesis of infectious disease. Variations in INFGR1 were related to several diseases. The results showed that the presence of GG allele is accompanied by a decrease in susceptibility to chronic HBV infection.

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  Background: In spite of designing and applying an effective vaccine against Hepatitis B virus (HBV), chronic infection with this virus is still one of the most important health problems worldwide. Host genetic background including single nucleotide polymorphisms play a significant role in chronicity or clearance of the infection. The final product of programmed cell death 1 gene (PDCD1) is expressed frequently on T-cells and in chronic viral infections, prevent the virus-specific T-cell response against the virus. In this study, the association of a single nucleotide polymorphism (+7146A/G) in intron 4 of PD1 gene with chronic hepatitis B infection in Iranian population has been assessed.

  Materials and Methods: 212 chronic HBV patients and 208 healthy controls were analyzed in this case-control study. Genomic DNA of the studied individuals was extracted and after performing polymerase chain reaction (PCR), polymorphism of +7146 was determined via RFLP method.

  Results: Frequencies of GG, GA and AA genotypes on position 7146 of the intron 4 of PD1 gene were 77.4%, 20.7% and 1.9% in patient group and 80.8%, 15.4% and 3.8% in control group, respectively. After statistical analysis, No significant difference was observed between patient and control groups (p=0.198).

  Conclusion: Genotype frequencies in the studied population are in accordance with the results of previous studies. Results of the present study suggest that there is not any association between A/G single nucleotide polymorphism in intron 4 of PD1 gene and susceptibility to chronic hepatitis B in Iranian population.

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Background: Hepatitis B virus (HBV) is a member of hepadenaviridae family, which is infectious for humans and a few animal species. Successful clearance and elimination of infection from the body or development of HBV infection to chronic disease depend on the host genetic background in immune system genes. Interleukin-12 (IL12) and also Interleukin-12 Receptor B1 (IL 12 RB1) are the key factors in the spontaneous clearance of viral infections, especially HBV. The aim of the present research is to investigate the association between Interleukin-12 receptor B1 gene polymorphism (rs11575934 A/G) and susceptibility to chronic Hepatitis B virus infection.

Materials and Methods: In this case-control study, genomic DNA of 150 chronic HBV infected patients and 150 healthy controls were extracted from peripheral blood cells. Single nucleotide polymorphism (rs11575934 A/G) was genotyped using polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP).

Results: The frequency of GG, AG, AA genotypes was 6.7%, 40.7%, and 52.7% in chronic patients and 12.7%, 41.3%, and 46% in control group, respectively. No statistically significant difference between case and control groups has been observed (p=0.176).

Conclusion: In the present study, no significant correlation between rs11575934 A/G single nucleotide polymorphism of the IL12RB1 gene and susceptibility to chronic hepatitis B virus infection has been observed. According to the study, this polymorphism does not affect the susceptibility to chronic HBV infection.

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Background: Hypervariability of hepatitis C virus (HCV) proteins is an important obstacle to design an efficient vaccine for the infection. To construct a protective vaccine against HCV, a DNA vaccine containing conserved epitopes of the virus was designed. To enhance the induced immune responses, adjuvant activity of N-terminal domain of gp96 (NT(gp96)) was used.

Materials and Methods: A multi-epitope (PT) DNA vaccine encoding four HCV immunodominant cytotoxic T lymphocyte epitopes (HLA-A2 and H2-D^d) from Core, E2, NS3 and NS5B antigens in addition to a T-helper CD4+ epitope from NS3 protein and a B-cell epitope from E2 protein was designed and constructed. Then, NT(gp96) was fused to the PT DNA (PT-NT(gp96)). The stimulated cellular and humoral immune responses of PT and PT-NT(gp96) were evaluated in mice model.

Results: According to multicolor flow cytometry assay, the frequency of CD8+ T-cells producing IFNγ and TNFα in the splenocytes of immunized mice with PT-NT(gp96) (6.8%, 4%) was significantly higher than those of immunized with PT (0.9% , 0.8%), respectively. The same results have obtained in hepatic lymphocytes of the vaccinated mice. The level of IgG, IgG1 and IgG2a in the mice vaccinated with PT-NT (gp96) was significantly higher than the value obtained from the mice immunized with PT.

Conclusion: The results showed that PT DNA vaccine induces immune responses in mice model. Fusion of NT (gp96) to PT DNA vaccine causes to enhance cellular and humoral immune responses against HCV compared to sole PT vaccine.

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Background: Parvovirus 4 (PARV4) was first discovered in 2005, in a hepatitis B virus–infected injecting drug user (IDU). To date, the best evidence about PARV4 transmission is parenteral roots and comes from IDU individuals. It seems that the prevalence of the virus in the normal population is very low. In this study, we investigated the prevalence of PARV4 virus among patients with chronic HCV infection compared with healthy controls and related risk factors among these groups.

Materials and Methods: A total of 206 patients, including 103 patients with chronic HCV infection and 103 healthy controls, were studied by use of nested-PCR and also real-time PCR techniques.

Results: AST enzyme levels with a mean of 40.45+34.84 and 18.58+5.9 in patients and healthy group respectively and the amount of enzyme ALT among patients with a mean of 40.45+35.75 and 21.50+11.35 in patients and healthy group respectively, were reported. Finally, after screening all DNA samples from patients and controls, we discovered that none of these people are infected with the PARV4 virus.

Conclusion: This study is the first to investigate the occurrence of PARV4 among HCV patients in Iran. The results show that, the virus is not important in Iranian population, even in patients with blood born infections such as HCV and further studies in other areas and various groups are required.

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On average, patients suffering from non-alcoholic steatohepatitis after about seven years, their disease turns into fibrosis and reversibility at this stage becomes very difficult because this disease is an irreversible stage of the disease. Fatty liver is non-alcoholic (2). Researches have come to the conclusion that liver inflammation and insulin resistance decrease and insulin sensitivity increases with sports activity (3). TNF-α has a high inflammatory effect; So that different agents and species of this family and their receptors play a role in NASH disease and liver fibrosis (5). However, exercise increases prostaglandins and cAMP. The mentioned hormones inhibit the function of TNF-α (6). On the other hand, anti-inflammatory cytokines increase due to exercise and inhibit the increase of TNF-α. With the increase in production and secretion of TNF-α, other inflammatory factors such as TGF-β1 signaling are activated and fibrosis signaling will start in liver cells (5). TGF-β1 (Transforming growth factor beta 1) is one of the members of the large family of transforming growth factors beta (TGF-β) and a key cytokine in obesity and insulin resistance (7). In a research, during 48 weeks of applying a high-fat diet to rats, they found that steatosis occurs in the liver of rats from the eighth week onwards, and the amount of TGF-β1 in them increased significantly. In the end, they came to the conclusion that this factor can be one of the main characteristics of determining the degree of liver fibrosis in patients with NASH (10). High-intensity interval training (HIIT) is one of the new training models whose positive effects have been identified in a variety of metabolic diseases (13). On the other hand, there are very few researches about the effect of aquatic environment and swimming on the improvement of metabolism and inflammation in NASH patients. Based on the results of a systematic review in 2018, it was shown that endurance exercise in water improved systemic inflammation and weight control (18). Despite the conflicting results in this field and the beneficial effects of exercise in water and also human's innate interest in water, the effect of high-intensity interval exercise in water in patients with non-alcoholic steatohepatitis has not been observed by the researchers of this study. Therefore, the effect of eight weeks of high-intensity interval training in water on inflammatory factors in patients with non-alcoholic steatohepatitis was investigated.
Materials and methods
In this study, eight-week-old rats were divided into two groups: healthy (n=20) and high-fat diet (HFD) (n=20). After eight weeks and proof of disease induction, the HFD group was randomly divided into two groups: control-disease (n=9) and exercise-disease (n=9); Also, the healthy group was divided into two groups: control-healthy (n=9) and exercise-healthy (n=9). The rats in the training group performed HIIT swimming training, including 20 times of 30 seconds of swimming with 30 seconds of rest between each time, for eight weeks (three days a week). One-way ANOVA and Bonferroni's post hoc test (P<0.05) were used to determine the difference between groups.
Ethical Considerations
The proposal of this study has been approved by the Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.REHAB.REC.1400.008).
Findings:
As shown in diagram 1; Based on the results of the one-way analysis of variance test, it can be said that there was a significant difference between the mean TNF-α blood serum (P=0.001). According to the results of Bonferroni's post hoc test, these differences in blood serum TNF-α variable between the control-healthy and control-disease groups (P=0.001), exercise-disease (P=0.001) and exercise-healthy (P=0.002), control-disease with exercise-disease (P=0.012) and exercise-healthy (P=0.001), exercise-healthy with exercise-disease (P=0.002) was.
According to graph 2, it can be seen that there is no significant difference in TGFβ1 variable in all four groups (p=0.068). However, by comparing the averages, it is found that the amount of TGFβ1 protein has decreased by 49.1968% in the patient-exercise group after high-intensity intermittent swimming exercise compared to the control-patient group. Meanwhile, this protein in the exercise-healthy group was reduced by 45.2741% compared to the control-patient. Figure 1 shows the protein bands related to TGFβ1 protein.
Discussion and conclusion: The results of the present research showed that high-intensity intermittent swimming exercises reduce inflammatory and fibrotic factors, and in general, it can be concluded that eight weeks of high-intensity intermittent swimming exercises improve the inflammatory and fibrotic factors associated with non-alcoholic steatohepatitis. . However, to obtain a definitive result, this type of exercise should be studied in human studies in this patient community.
Appreciation and thanks: This article is taken from the master's thesis in sports physiology (first author) of Zand Institute of Higher Education, Shiraz, with ethics code IR.SUMS.REHAB.REC.1400.008. In the end, we sincerely thank all friends and colleagues who helped us during the stages of this research.
Conflict of interest:The authors of this article have no mutual benefit from its publication.
Authors' share (participation rate): All four authors participated in the preparation of this article.
Key words: high-intensity swimming interval training, non-alcoholic steatohepatitis, tumor necrosis factor alpha, transforming growth factor beta