• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3879-3884
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• 2014

Background: In chronic hepatitis B (CHB), the presence of hepatic steatosis (HS) seems to be associated with known host and viral factors which may influence the long-term prognosis of chronic hepatitis B (CHB), probably leading to cirrhosis and hepatocellular carcinoma (HCC). Different from chronic hepatitis C (CHC), factors associated with HS in CHB are not clearly explored. Materials and Methods: 160 CHB patients were divided into two groups depending on the results of liver biopsy. Group I consisted of 71 patients with confirmed steatosis. Group II comprised 89 patients without steatosis. The groups were compared in terms of basal characteristics, body mass index (BMI), liver enzymes (ALT, AST, ALP), serum fasting blood sugar (FBS) and lipids, hepatitis B e antigen (HBeAg), viral load, and histological findings. Results: In terms of host factors, male gender, older age, BMI, high serum FBS and lipid levels were associated with HS. On the other hand, ALT levels, the HAI scores of necroinflammation and stage of fibrosis did not associate with HS. On multivariate analysis, parameters of sex, BMI, cholesterol and FBS levels were independently associated with HS. Regarding viral factors, HBeAg negativity was significantly associated with HS (81.7%, p value 0.006), but not HBV DNA level (p value 0.520). Conclusions: HS in CHB appears to be unrelated to the status of HBV replication. However, fibrosis progression in CHB is related to variable host factors. HS may be enhanced through these factors in HBV chronic patients.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.375-383
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• 2013

Hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) and hepatitis C virus (HCV) infections is thought to account for more than 80% of primary liver cancers. Both HBV and HCV can establish chronic liver inflammatory infections, altering hepatocyte and liver physiology with potential liver disease progression and HCC development. Cyclophilin A (CypA) has been identified as an essential host factor for the HCV replication by physically interacting with the HCV non structural protein NS5A that in turn interacts with RNA-dependent RNA polymerase NS5B. CypA, a cytosolic binding protein of the immunosuppressive drug cyclosporine A, is overexpressed in many cancer types and often associated with malignant transformation. Therefore, CypA can be a good target for molecular cancer therapy. Because of antiviral activity, the CypA inhibitors have been tested for the treatment of chronic hepatitis C. Nonimmunosuppressive Cyp inhibitors such as NIM811, SCY-635, and Alisporivir have attracted more interests for appropriating CypA for antiviral chemotherapeutic target on HCV infection. This review describes CypA inhibitors as a potential HCC treatment tool that is contrived by their obstructing chronic HCV infection and summarizes roles of CypA in cancer development.

• Journal of Life Science
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• v.32 no.2
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• pp.94-100
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• 2022

Chronic infection by hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype, adaptive mutations, and environmental factors. The pregenomic RNA transcription of HBV for their replication is regulated by the core promoter activation. Core promoter mutations have been the reason for acute liver failure and are associated with HCC development. We obtained HBV genes from a patient in Myanmar who was infected with HBV and identified gene variations in the core promoter region. For measuring the relative transactivation activity of the core promoter, we prepared the core-promoter reporter construct. Among the gene variations of the core promoter, the mutations of C1731T and G1806A were associated with increase in the transactivation of the HBV core promoter. Through computer analysis for searching for a tentative transcription factor binding site, we showed that the mutations of C1713T and G1806A newly created C/EBPβ and XBP1-responsive elements of the core promoter, respectively. The ectopic expression of C/EBPβ largely increased the HBV core promoter containing the C1713T mutation and that of XBP1 activated the M95 promoter containing the G1806A mutation. Our efforts to treat and prevent HBV infections are hampered by the emergence of drug-resistant mutations and vaccine-escape mutations. Our results provide the biological properties and clinical significance of specific HBV core promoter mutations.

• IMMUNE NETWORK
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• v.10 no.4
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• pp.126-134
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• 2010

Background: $CD8^+$ T cells contribute to the clearance of Hepatitis B virus (HBV) infection and an insufficient $CD8^+$ T cell response may be one of the major factors leading to chronic HBV infection. Since the HBx antigen of HBV can up-regulate cellular expression of several immunomodulatory molecules, we hypothesized that HBx expression in hepatocytes might affect $CD8^+$ T cell activity. Methods: We analyzed the activation and apoptosis of $CD8^+$ T cells co-cultured with primary hepatocytes rendered capable of expressing HBx by recombinant baculovirus infection. Results: Expression of HBx in hepatocytes induced low production of $interferon-{\gamma}$ and apoptosis of CD8+ T cells, with no effect on CD8 T cell proliferation. However, transcriptional levels of H-2K, ICAM-1 and PD-1 ligand did not correlate with HBx expression in hepatocytes. Conclusion: Our results suggest that HBx may inhibit $CD8^+$ T cell response by regulation of $interferon-{\gamma}$ production and apoptosis.

• Clinical and Experimental Pediatrics
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• v.50 no.4
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• pp.348-354
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• 2007

Purpose : Perinatal hepatitis B viral infection is decreasing; however, 10% of babies to HBeAg positive mothers still become chronic carriers despite perinatal prophylaxis. Although, the cause of prophylaxis failure is still unclear, an importance of maternal HBV-DNA level at the delivery time has been suggested. This study was established to certify if it would be a useful predictable factor for the outcome of perinatal prophylaxis. Methods : Twenty-nine HBeAg positive mothers whose babies had known outcomes of prophylaxis were selected. To determine the amount of maternal HBV-DNA, a quantitative PCR was performed with the WHO International Standard for HBV DNA NAT assays. Results : The mean logarithm HBV-DNA level of mothers with failed outcomes was significantly higher than that of mothers with succeessful outcomes (7.99 vs. 6.72, P=0.015). The predictable maternal HBV-DNA cut-off level to prophylaxis outcome was $2.83{\times}10^7copies/mL$ (100 pg/mL). None out of the case 16 (0%) who had below this level, and 5 out of 13 (38.5%) who had above this level of maternal HBV-DNA failed in perinatal prophylaxis. Conclusion : Mothers with higher levels of HBV-DNA at delivery time would be prone to a worse outcome of prophylaxis using the conventional approach. Perinatal prophylaxis failure rate can be reduced, if we try to introduce more potent prophylactic treatment into the cases with this risk factor.

• Korean Journal of Microbiology
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• v.49 no.3
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• pp.221-227
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• 2013

Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) cause viral infections that lead to chronic diseases. When they invade human body, virus specific T cells play an important role in antiviral effector functions including killing virus-infected cells and helping B cells to produce specific antibodies against viral proteins. The antiviral activity of T cells is usually affected by immune-regulatory factors that express on surface of T cells. Recently, many researchers have investigated the relationship between effector functions of virus specific T cells and characteristics of immune regulatory factors (e.g., CD28, CD25, CD45RO, FoxP3, PD-1, CTLA-4). In particular, Immune inhibitory molecules such as forkhead box P3 (FoxP3), programmed death-1 (PD-1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with T-cell dysfunction. They are shown to be up-regulated in chronic viral diseases such as hepatitis B, hepatitis C or human immunodeficiency virus infection. Therefore, the positive correlation between viral persistence and expression of immune regulatory factors (FoxP3, PD-1, and CTLA-4) has been suggested. In this review, the roles of immune regulatory factors FoxP3, PD-1, and CTLA-4 were discussed in chronic viral diseases such as HIV, HBV, or HCV.

• Journal of Microbiology and Biotechnology
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• v.11 no.2
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• pp.186-192
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• 2001

A primary culture of human fetal hepatocytes was obtained through a therapeutic abortion process at 26 weeks of gestation period. More than $10^8$ cells were seeded on a plastic plate. These hepatocytes were infected with hepatitis B virus (HBV). The HBV was purified from serum of one chronic HBV carrier. Transformed hepatocytes were subcultured in a 10% FBS-supplemented medium. The morphology of the transformed cell was epithelial-like. The cells from the first pass showed signs of early proliferation and had a latent period of more than 3 months after 6-7 passages. After the rest period, the transformed cell proliferated actively and they were subcultured every three days. Transformed hepatocytes were characterized by detection of the HBV transcript by RT-PCR. The secretion of virions from transformed cells was investigated by PCR with the cell medium. Two types of virions secreted into the culture medium were examined by using the transmission electron microscope. Another approach to study the secretion of virions in to culture medium was carried out with HBV antibody. HBsAg was detected in the culture medium of transformed cells using ELISA and Western blot analyses. These data suggested that the human fetal hepatocyte cell line has been established by infection of HBV, in which this cell line secreted viral particles into the culture medium.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.5955-5958
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• 2012

Hepatocellular carcinoma (HCC), the sixth most prevalent cancer worldwide, continues to have high prevalence in many countries of Asia. The main challenge is the high prevalence of chronic hepatitis and aflatoxin, for example in China. HBV vaccination should be the major preventive tactic in Asian countries. The burden of HCC is low in Iran because most cases are due to HBV and this infection was less common. Although in Iran, a mass vaccination program started in 1993, its impact on decreasing the burden of HCC due to HBV can only be expected in future decades.

• Radiation Oncology Journal
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• v.28 no.2
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• pp.106-110
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• 2010

Reactivation of the hepatitis B virus (HBV) is a well-recognized complication in patients with chronic HBV infection who receive cytotoxic or other immunosuppressive therapy. In cases of patients treated by radiotherapy however, only a few of such reports exist and most of these include the patients previously treated by chemotherapy or transarterial chemoembolization. The results of this study point to a case of a patient with reactivation of HBV after radiotherapy alone. This study shows the possibility of HBV reactivation by partial hepatic irradiation alone hence, special attention should be paid to patients with HBV disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4765-4771
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• 2014

Background: Patients with chronic liver diseases (CLD) may have compromised health related quality of life (HRQoL). Hepatitis B virus (HBV) infection has long been the leading cause of CLD including liver cancer and cirrhosis. Knowledge on different symptom profiles of CLD should help in development of comprehensive treatment and patient care plans. Objective: To access the facets of HRQoL in chronic liver diseases throughout their spectrum of severity. Materials and Methods: A cross-sectional study was conducted in the First Affiliated Hospital of Kunming Medical University in Yunnan Province of China. Both out- and inpatients undergoing treatment protocols for different HBV related liver disease states were consecutively collected from December 2012 to June 2013. ANOVA was used to compare the mean scores of EQ-5D and chronic liver disease questionnaire (CLDQ) among 5 disease groups. The relationship between demographic variables predicting global CLDQ scores and the domains of CLDQ was analysed. Results: A total of 1040 patients including 520 without complications, 91 with compensated cirrhosis, 198 with decompensated cirrhosis, 131 with HCC and 100 with liver failure were recruited. All domains of CLDQ, the means of EQ-5D value and EQ VAS exhibited significant decline with worsening of disease severity from uncomplicated HBV to liver failure. The multivariate regression demonstrated the reduction of mean scores of CLDQ domain at advanced stage. Patients with liver failure and HCC had more HRQoL impairment than other disease states. No effect of patient gender was found. Patient age was associated with 'fatigue' and 'worry' domains (p=0.006; p=0.004) but not with other domains and global scores of CLDQ and ED-5D. Conclusions: The HRQoL in chronic hepatitis B patients is greatly affected by disease states. Care for HBV-related diseases should consider not only the outcomes of treatment strategies but also improvement in patient wellbeing.