• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9635-9641
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• 2014

Background: This retrospective study was aimed to investigate the efficacy of prophylactic agents in hepatocellular carcinoma (HCC) patients receiving TACE and compare the difference between lamivudine and entecavir. Materials and Methods: A consecutive series of 203 HBV-related HCC patients receiving TACE were analyzed including 91 patients given prophylactic agents. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 IU/ml higher than the nadir level, hepatitis flares due to HBV reactivation and progression free survival (PFS) were the main endpoints. Results: Some 48 (69.6%) reached virologic response. Prophylaxis significantly reduced virologic events (8.8% vs 58.0%, p=0.000) and hepatitis flares (1.1% vs 13.4%, p=0.001). Patients presenting undetectable HBV DNA levels displayed a significantly improved PFS as compared to those who never achieved undetectable HBV DNA. Prophylaxis and e-antigen positivity were the only significant variables associated with virologic events. In addition, prophylaxis was the only independent protective factor for hepatitis flares. Liver cirrhosis, more cycles of TACE, HBV DNA negativity, a lower Cancer of the Liver Italian Program score, non-metastasis and no hepatitis flares were protective factors for PFS. Prophylactic lamivudine demonstrated similar efficacy as entecavir. Conclusions: Prophylactic agents are efficacious for prevention of HBV reactivation in HCC patients receiving TACE. Achievement of undetectable HBV DNA levels displayed a significant capability in improving PFS. Moreover, persistent tumor residual lesions, positive HBV DNA and hepatitis B flares might be causes of tumor progression in these patients.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.126-135
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• 2003

Background: One of the important factors in the prognosis of chronic hepatitis B patient is the degree of replication of hepatitis B virus (HBV). It has been known that HBV DNA polymerase plays the essential role in the replication of HBV. HBV DNA polymerase is composed of four domains, TP (Terminal protein), spacer, RT (Reverse transcriptase) and RNaseH. Among these domains, tyrosine, the $65^{th}$ residue of TP is an important residue in protein-priming reaction that initiates reverse transcription. If monoclonal antibody that recognizes around tyrosine residue were selected, it could be applied to further study of HBV replication. Methods: To produce TP-specific scFv (single-chain Fv) by phage display, mice were immunized using synthetic TP-peptide contains $57{\sim}80^{th}$ amino acid residues of TP domain. After isolation of mRNA of heavy-variable region ($V_H$) and light-chain variable region ($V_L$) from the spleen of the immunized mouse, DNA of $V_H$ and $V_L$ were obtained by RT-PCR and joined by a DNA linker encoding peptide (Gly4Ser)3 as a scFv DNA fragments. ScFv DNA fragments were cloned into a phagemid vector. scFv was expressed in E.coli TG1 as a fusion protein with E tag and phage gIII. To select the scFv that has specific affinity to TP-peptide from the phage-antibody library, we used two cycles of panning and colony lift assay. Results: The TP-peptide-specific scFv was isolated by selection process using TP-peptide as an antigen. Selected scFv had 30 kDa of protein size and its nucleotide sequences were analyzed. Indirect- and competitive-ELISA revealed that the selected scFv specifically recognized both TP-peptide and the HBV DNA polymerase. Conclusion: The scFv that recognizes the TP domain of the HBV DNA polymerase was isolated by phage display.

• The Korean Journal of Blood Transfusion
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• v.23 no.2
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• pp.152-161
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• 2012

Background: Since Jan. 2012, for performance evaluation of viral reagents, analysis of domestic samples has been recommended in order to obtain approval from the KFDA when they are first introduced to Korea. This regulation requires the standard domestic materials driven from locally infected samples. We tried manufacturing the plasma working standards of HBV, HCV, and HIV NAT using a mixed titer of viral loads. Methods: Forty three HBV DNA positive plasmas, 25 HCV RNA positive plasmas, and 26 HIV RNA positive plasmas were evaluated according to viral load and genotype. Several plasma units, which had high-titer viral loads and the common viral genotypes in Korea, were selected as the source materials for each viral standard. To adjust the appropriate concentration based on the detectable range of variable viral reagents, the source plasma was diluted to several concentrations, divided into small vials, and analyzed for quantification. Results: The 13 plasma working standards, which had variable viral loads for the mixed titer performance panel of HIV, HCV, and HBV NAT, were produced. Conclusion: These national standard materials were first produced in order to supply the mixed titer performance panel for the viral NAT reagent of the level IV transfusion related high-risk group in Korea.

• BMB Reports
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• v.37 no.2
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• pp.167-176
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• 2004

Although efficient antiviral lamivudine is used for HBV-infected patients, a prolonged treatment with nucleoside analogs often results in lamivudine-resistant variants. In this study, we evaluated the fidelity of the lamivudine-resistant variants. The FLAG-tagged wild-type (FPolE) and Met550 variants (FPolE/M550A, M550V, and M550I) of HBV DNA polymerases were expressed in insect cells then purified. Like many other reverse transcriptases, no $3'{\rightarrow}5'$ exonuclease activity was detected in the HBV DNA polymerase. Since there is no proofreading activity, then the use of the site-specific nucleotide misincorporation method is beneficial. From the $f_{ins}$ value analysis, it is evident that M550I and M550V exhibit higher fidelity values than the wild-type HBV DNA polymerase, while M550A exhibits similar fidelity values. It is therefore suggested that lamivudine resistance comes from the stringency to dNTP binding and the discrimination of dCTP and lamivudine in M550V and M550I.

• Bulletin of the Korean Chemical Society
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• v.30 no.3
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• pp.577-581
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• 2009

Interactions between the surface and capsid proteins of the hepatitis B virus (HBV) are critical for the assembly of virus particles. In this study, we developed a cell-based method to visualize the interactions between the capsid and surface proteins of HBV. Capsid-GFP, a capsid protein fused to a green fluorescence protein (GFP), forms nucleocapsid-like structures in the cytoplasm of mammalian cells. It relocates to the plasma membranes in cells expressing PH-PreS, a fusion protein consisting of the PreS region of the HBV surface protein and the PH domain of PLC-$\gamma$. Membrane localization of the capsid-GFP in these cells is prevented by an inhibitory peptide that blocks the interaction between the capsid and surface proteins. This dynamic localization of capsid-GFP is applicable for screening compounds that may potentially inhibit or prevent the assembly process of HBV particles.

• 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.

• BMB Reports
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• v.55 no.5
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• pp.220-225
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• 2022

Hepatocellular carcinoma (HCC), a primary type of liver cancer, is one of the leading causes of cancer related deaths worldwide. HCC patients have poor prognosis due to intrahepatic and extrahepatic metastasis. Hepatitis B virus (HBV) infection is one of the major causes of various liver diseases including HCC. Among HBV gene products, HBV X protein (HBx) plays an important role in the development and metastasis of HCC. However, the mechanism of HCC metastasis induced by HBx has not been elucidated yet. In this study, for the first time, we report that HBx interacts with the suppressor of cytokine signaling 1 (SOCS1) which negatively controls NF-κB by degrading p65, a subunit of NF-κB. NF-κB activates the transcription of factors associated with epithelial-mesenchymal transition (EMT), a crucial cellular process associated with invasiveness and migration of cancer cells. Here, we report that HBx physically binds to SOCS1, subsequently prevents the ubiquitination of p65, activates the transcription of EMT transcription factors and enhance cell migration and invasiveness, suggesting a new mechanism of HBV-associated HCC metastasis.

• Journal of Yeungnam Medical Science
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• v.2 no.1
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• pp.211-220
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• 1985

Serum HBsAg, AntiHBs, HBeAg, AntiHBe and AntiHBc were detected by radioimmunoassay in 39 patients with acute viral hepatitis, 79 patients with chronic hepatitis, 30 patients with liver cirrhosis, 16 patients with primary hepatocellular carcinoma, 14 patients of HBsAg carriers and 129 cases of controls:78 cases of normal level of SGOT, SGPT, and 51 cases of elevated level of SGOT, SGPT. Following results were obtained: 1. HBsAg was detected in 66.7% of acute viral hepatitis, 63.3% of chronic hepatitis, 36.7% of liver cirrhosis, 81.3% of primary hepatocellular carcinoma and 27.1% of controls. 2. AntiHBs was positive in 0% of acute viral hepatitis, 21.5% of chronic hepatitis, 36.7% of liver cirrhosis, 31.3% of primary hepatocellular carcinoma, 0% of carrier and 44.2% of controls. 3. HBeAg was detected in 45.6% of chronic hepatitis, 23.3% of liver cirrhosis and 31.3% of primary hepatocellular carcinoma. 4. Among chronic liver diseases, antiHBe was positive in 56.3% of primary hepatocellular carcinoma, 23.3% of liver cirrhosis and 20.3% of chronic hepatitis. 5. AntiHBc was detected in most of all examines and the significance of presence of AntiHBc does not seem to represent liver disease itself but the evidence of infection of HBV. 6. Among 14 HBV carriers, 6 cases presented with abnormal SGOT, SGPT. 7. All HBV markers were negative in 5.1% of acute viral hepatitis, 5.1% of chronic hepatitis and 14.7% of controls: 17.6% of subjects with abnormal SGOT, SGPT and 12.8% of subjects with normal SGOT, SGPT. 8. Beside of HBV, other causes, such as non A, non B virus, Delta-agent, other viruses or related factors should be excluded among the patients with evidence of HBV infection associated with elevation of SGOT & SGPT.

• Proceedings of the Korean Biophysical Society Conference
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• 1996.07a
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• pp.32-32
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• 1996

Molecular docking studies were performed for a humanized HBV Pre-S2 antibody and its antigen adr. Antigen structure was taken from NMR experiment and antibody structure was determined by using homology technique. At first step, Grid search was performed for finding energetically favorable orientations antigen. (omitted)

• Journal of Life Science
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• v.2 no.3
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• pp.163-173
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• 1992

간염바이러스들은 이들의 virology 및 임상적 특징들에 따라 A형, B형, C형, D형 및 E형으로 분류되며, A형 및 E형은 미개발국가들의 약년층에서 흔히 발생하는 급성간염의 원인으로 알려져 왔으나 만성간염 또는 간세포 암의 원인은 되지 않음으로 B형 및 C형에 비해 임상적인 의의는 적다. B형 바이러스는 급성간염 및 간세포 암의 가장 중요한 원인이며 전세계 인구 중에서 3억가량이 HBV에 감염되어 있고 이들의 75%가 아시아인인 것으로 밝혀져 있다. C형 바이러스는 최근에 비A형, 비B형 간염바이러스에 의한 간염의 중요한 원인으로 밝혀졌으며 구미 및 일본에서는 만성간염 및 간세포암의 가장 중요한 원인으로도 간주되고 있다. D형 간염바이러스는 지중해 연안국가, 북아프리카 및 중동국가들에서 HBV에 의해 이미 감염되어 있는 환자들을 침범함으로써 HBV에 의한 급성 및 만성간염을 악화시키나 HDV 단독으로는 간염의 원인이 될 수는 없다고 알려져 있다. 본지에서는 한국인에게서 임상적인 의의를 갖는 HBV에 대해 구체적으로 기술한다.