• 대한예방의학회:학술대회논문집
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• 대한예방의학회 2000년도 제52차 추계학술대회 연제집
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• pp.116-117
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• 2000

• IMMUNE NETWORK
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• 제5권1호
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• pp.1-10
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• 2005

Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3923-3927
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• 2016

Infection with the hepatitis C virus is a major public health concern which can lead to carcinoma and liver failure. It has been shown that single nucleotide polymorphisms can affect the level of gene activity of tumor necrosis factor (TNF) which has an important role, especially in viral infections which can lead to apaptosis of infected hepatocellular cells. We investigated the impact of three possible genotypes for rs1800629 or A/G single nucleotide polymorphism located downstream of $TNF{\alpha}$ gene promoter in groups of control (n=76) and chronic hepatitis C patients (n=89) focusing on the response to treatment among sensitive and resistant groups. Genomic DNA was extracted from $500{\mu}l$ prepheral whole blood and PCR and RFLP were used to amplify the region of interest and genotyping. With statistical analyzes a p-value <0.05 was considered meaningful. There was no significant difference in distribution of possible three genotypes among healthy individuals and patients (P=0.906, OR=1.194, CI=0.063-22.790). However, the frequency of G allele was higher in patients whereas A allele was more common among healthy individuals (p<0.0001). Further studies with more samples seem to be necessary.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.35-39
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• 2015

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers in South East Asian countries including Cambodia, where prevalence of chronic carriers of hepatitis B and C virus (HBV and HCV) is reported to be very high. We reviewed HCC cases admitted to a cancer hospital in Phnom Penh, which is the only one hospital for cancer treatment and care in Cambodia during the study period. Materials and Methods: Information was collected from medical records of 281 cases (210 males and 71 females) diagnosed as primary HCC from 2006 to 2011. Results: The subjects were 7-81 years old with a median age of 53 years. Hypochondriac pain was the most common complained symptom (74%). One third of the cases presented with jaundice. Nearly half had ascites at their first visit. One third had liver cirrhosis. Nearly three fourths of the cases presented with tumor sized more than 50 mm in diameter, and in almost all cases (97.4%) the size was more than 20 mm. Among 209 subjects tested, hepatitis virus carriers were 75.6%; 46.4% for HBV only, 21.5% for HCV only, and 7.7% for both viral infections. Median age of patients with HBV was about ten years younger than those with HCV. Conclusions: This study revealed the characteristics of HCC cases in Cambodia, although there were several limitations. Most HCC cases were infected with HBV and/or HCV, and diagnosed at late stages with complications. This implicated that public health intervention to prevent HBV and HCV infection is of high priority.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8837-8842
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• 2014

Background: Hepatitis C virus (HCV) infection is an important cause of liver cancer in Thailand. The highest prevalence of anti-HCV positive among Thai blood donors is found in the northeastern region. The present analysis of the genotype distribution among anti-HCV positive northeastern-Thai blood donors was conducted to provide a base for the epidemiological pattern of HCV infection in this region. Materials and Methods: A total of 112 HCV seropositive healthy blood donors were randomly selected and tested for the presence of HCV-RNA by RT-PCR. HCV-RNA positive samples were genotyped by direct sequencing at core region genomes and confirmed by phylogenetic analysis. Results: HCV viremia was found in 94.6% (106/112) of HCV seropositive blood donors. There were 3 major genotypes distributed among this population. HCV genotype 3a was the most prevalent (71.7%) followed by genotypes 1a (7.5%), 1b (7.5%), 6i (3.8%), 6f (2.8%) and 6n (1.9%). Conclusions: HCV genotype 3a in asymptomatic infections in northeastern Thailand is significantly higher than other previous reports. Subgenotype 6 prevalence is less than in neighboring countries and distribution patterns differ. The findings are relevant as predictors for using interferon therapy in this population.

• Journal of Microbiology and Biotechnology
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• 제28권9호
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• pp.1554-1562
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• 2018

The type I interferons (IFNs) play a vital role in activation of innate immunity in response to viral infection. Accordingly, viruses have evolved to employ various survival strategies to evade innate immune responses induced by type I IFNs. For example, hepatitis E virus (HEV) encoded papain-like cysteine protease (PCP) has been shown to inhibit IFN activation signaling by suppressing K63-linked de-ubiquitination of retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1), thus effectively inhibiting down-stream activation of IFN signaling. In the present study, we demonstrated that HEV inhibits polyinosinic-polycytidylic acid (poly(I:C))-induced $IFN-{\beta}$ transcriptional induction. Moreover, by using reporter assay with individual HEV-encoded gene, we showed that HEV methyltransferase (MeT), a non-structural protein, significantly decreases RIG-I-induced $IFN-{\beta}$ induction and $NF-{\kappa}B$ signaling activities in a dose-dependent manner. Taken together, we report here that MeT, along with PCP, is responsible for the inhibition of RIG-I-induced activation of type I IFNs, expanding the list of HEV-encoded antagonists of the host innate immunity.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.235-238
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• 2016

Hepatitis C is an ailment of liver caused by hepatitis C virus (HCV) infection. About 3% of the world population is infected by this virus. HCV infection is a leading reason for liver cirrhosis and therefore a major source of hepatocellular carcinoma. The study focused on the incidence of active HCV infection in blood donors of Mardan district of KPK, Pakistan. A total of 5318 blood donors were inspected for the presence of anti-HCV antibodies and HCV-RNA using ICT (immune-chromatographic test), ELISA and RT-PCR at Mardan Medical Complex (MMC), Mardan. Out of these, 157 (2.95%) were positive by ICT, 60 (1.12%) by ELISA and 56 (1.05%) for HCV-RNA. The frequency of active HCV infectivity amongst the blood donors from district Mardan, KPK Pakistan was 1.05 %. Application of strict measures during blood donor selection and use of proper screening assays such as ELISA in place of ICT devices can give a more accurate picture so that the incidence of this viral infection in HCV negative blood recipients can be reduced.

• Molecules and Cells
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• 제42권1호
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• pp.67-78
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• 2019

Methylation of HBV cccDNA has been detected in vivo and in vitro; however, the mechanism and its effects on HBV replication remain unclear. HBx derived from a 1.2-mer HBV replicon upregulated protein levels and enzyme activities of DNA methyltransferase 1 (DNMT1), 3a, and 3b, resulting in methylation of the negative regulatory region (NRE) in cccDNA, while none of these effects were observed with an HBx-null mutant. The HBx-positive HBV cccDNA expressed higher levels of HBc and produced about 4-fold higher levels of HBV particles than those from the HBx-null counterpart. For these effects, HBx interrupted the action of NRE binding protein via methylation of the C-1619 within NRE, resulting in activation of the core promoter. Treatment with 5-Aza-2′dC or DNMT1 knock-down drastically impaired the ability of HBx to activate the core promoter and stimulate HBV replication in 1.2-mer HBV replicon and in vitro infection systems, indicating the positive role of HBx-mediated cccDNA methylation in HBV replication.

• Journal of Microbiology and Biotechnology
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• 제28권8호
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• pp.1376-1383
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• 2018

The hepatitis B virus (HBV) envelope contains small (S), middle (M), and large (L) proteins. PreS1 of the L protein contains a receptor-binding motif crucial for HBV infection. This motif is highly conserved among 10 HBV genotypes (A-J), making it a potential target for the prevention of HBV infection. In this study, we successfully generated a neutralizing human monoclonal antibody (mAb), 1A8 (IgG1), that recognizes the receptor-binding motif of preS1 using a phage-displayed human synthetic Fab library. Analysis of the antigen-binding activity of 1A8 for different genotypes indicated that it can specifically bind to the preS1 of major HBV genotypes (A-D). Based on Bio-Layer interferometry, the affinity ($K_D$) of 1A8 for the preS1 of genotype C was 3.55 nM. 1A8 immunoprecipitated the hepatitis B virions of genotypes C and D. In an in vitro neutralization assay using HepG2 cells overexpressing the cellular receptor sodium taurocholate cotransporting polypeptide, 1A8 effectively neutralized HBV infection with genotype D. Taken together, the results suggest that 1A8 may neutralize the four HBV genotypes. Considering that genotypes A-D are most prevalent, 1A8 may be a neutralizing human mAb with promising potential in the prevention and treatment of HBV infection.

• Asian Pacific Journal of Cancer Prevention
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• 제16권8호
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• pp.3253-3256
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• 2015

Background: Chronic hepatitis B virus (HBV) infection related hepatocellular carcinoma (HCC) is a major health problem in the Asia-Pacific region including Thailand. Several factors have been proposed as contributing to hepatocarcinogenesis. This study was aimed to investigate the impact of CYP2C19 genotypic polymorphism in HCC related to chronic HBV infection in Thailand. Materials and Methods: A cross-sectional study was performed between April 2014 and January 2015. Chronic HBV patients with HCC (n=50) and without HCC (n=50) were included. Clinical information and blood samples of all patients were collected. The CYP2C19 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism method, and was classified as rapid metabolizer (RM), intermediate metabolizer (IM) or poor metabolizer (PM). Results: The CYP2C19 genotype frequencies of RM, IM and PM in HBV patients were found to be 19/50 (38%), 25/50 (50%) and 6/50 (12%), respectively. The CYP2C19 genotype frequencies of RM, IM and PM in HBV with HCC patients were 21/50 (42%), 25/50 (50%) and 4/50 (8%), respectively. The distribution of CYP2C19 genotype was not different between patients with and without HCC. Interestingly, among HBV with HCC patients, the RM genotype of CYP2C19 tended to increase risk of aggressive manifestation (OR=2.89, 95%CI=0.76-11.25, P-value=0.07), compared with non RM genotype carriers. Conclusions: CYP2C19 genotype IM was the most common genotype in Thai patients with chronic HBV infection. In addition, genotype RM could be an associated factor for aggressive presentation in HCC related to chronic HBV infection.