• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2395-2399
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• 2016

Background: Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Cytokines play an important role in the regulation of immune responses and defense against viral infections. Human interleukin 6 (IL6) is a multifunctional cytokine that participates in these processes. Objective: The aim of this study was to assess the IL6-174 gene polymorphism in patients with chronic hepatitis B virus (HBV) infection as compared with healthy controls in an Iranian population. Materials and Methods: Totals of 297 HBV patients and 368 control individuals were evaluated. Genomic DNA was extracted from peripheral blood and the SSP-PCR (sequence specific primer-polymerase chain reaction) method was applied for genotyping. Results: The frequencies of genotypes C/C, G/G and C/G in HBV cases were 4.7%, 34.3%, 60.9% and in controls were 12.8%, 39.7% and 47.6%, respectively. The frequencies of G and C allele in patients and controls were 78.1%, 21.9% and 67.4%, 32.6 % respectively. There was a significant difference in the frequencies of G/G genotype (CI=1.8-7.1, OR=3.47, P=0.00001) and G allele (CI=1.34-2.23, OR=1.72, P=0.0001) between HBV patients and the control group. Conclusions: These findings suggest that the IL6-174 C/G genotype and the G allele are strongly associated with susceptibility to HBV infection. Demographic information showed that most of the subjects were male (74.4%). According to high frequency of G/G genotype in male participants (63.1%) men probably are more susceptible to hepatitis than women.

• BMB Reports
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• v.38 no.2
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• pp.151-160
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• 2005

By a cDNA array representing 2308 signal transduction related genes, we studied the expression profiles of HeLa cells stably transfected by Hepatitis C virus nonstructural protein 4B (HCV-NS4B). The alterations of the expression of four genes were confirmed by real-time quantitative RT-PCR; and the aldo-keto reductase family 1, member C1 (AKR1C1) enzyme activity was detected in HCV-NS4B transiently transfected HeLa cells and Huh-7, a human hepatoma cell line. Of the 2,308 genes we examined, 34 were up-regulated and 56 were down-regulated. These 90 genes involved oncogenes, tumor suppressors, cell receptors, complements, adhesions, transcription and translation, cytoskeletion and cellular stress. The expression profiling suggested that multiple regulatory pathways were affected by HCV-NS4B directly or indirectly. And since these genes are related to carcinogenesis, host defense system and cell homeostatic mechanism, we can conclude that HCV-NS4B could play some important roles in the pathogenesis mechanism of HCV.

• Natural Product Sciences
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• v.2 no.2
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• pp.130-136
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• 1996

Evaluation of plant extracts that might inhibit hepatitis B virus (HBV) replication was performed to find potent anti-HBV agents. Eighty-five species of plants from forty-three families were tested for their anti-HBV activities using HBV-producing HepG2-derived 2.2.15 cells. The anti-HBV activity of plant extracts was measured by slot blot hybridization technique and cytotoxicity was determined by crystal violet staining procedure. All plants were extracted with methanol and the extracts were partitioned into n-hexane, ethyl acetate and aqueous layer. The ethyl acetate fractions of Rhus verniciflua $(stem:\;EC_{50},\;8.2{\mu}g/ml;\;CC_{50},\;9.4{\mu}g/ml)$, Gastrodia elata $(root:\;EC_{50},\;17.7{\mu}g/ml;\;CC_{50},\;>20{\mu}g/ml)$, Raphanus sativus $(seeds:\;EC_{50},\;17.3{\mu}g/ml;\;CC_{50},\;>20{\mu}g/ml)$, and Angelica gigas $(root:\;EC_{50},\;8.3{\mu}g/ml;\;CC_{50},\;15.6{\mu}g/ml)$ revealed the anti-HBV activity in 2.2.15 cell culture system and these fractions are under the process of further sequential fractionation by column chromatography to find the active principles against HBV.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.139-144
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• 1998

Abstract -Phyllanthus ussuriensis which belongs to Euphorbiaceae has been used as a component of Korean traditional remedy against hepatitis and jaundice. Aqueous methanolic extract of P. ussuriensis was tested for antiviral activity of hepatitis B virus (HBV) in HepG2 2.2.15 cells which were derived through transfection of cloned HBV DNA into HepG2 human hrpatoblastoma cells. P. ussuriensis extract decreased the levels of extracellular HBV virion DNA and inhibited HBV replication at concentrations ranging from 50 to 500$\mu$g/ml. Partitioning of water suspension of the extract revealed that the activity mainly resides in the EtOAc fraction. Consecutive purification of the EtOAc fraction by silica-gel column chromatography resulted in the two active anti-HBV fractions. Southern blot analysis shows that the action mechanisms or active site of the two fractions seems to be different in terms of their inhibition of HBV replication steps.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5463-5467
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• 2012

Hepatitis B virus (HBV) infection is contagious with transmissiobn vertically or horizontally by blood products and body secretions. Over 50% of Iranian carriers contracted the infection prenatally, making this the most likely route of transmission of HBV in Iran. To evaluate the resistance to adefovir (ADV) therapy in patients with chronic hepatitis B infection, a study was conducted on 70 patients (63 males and 7 females), who had received in first line lamivudine and second line adefovir. All were tested for the presence of hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), serum alanine amino transferase (ALT) level and HBV DNA load before and after treatment with ADV. In all samples, resistance to lamivudine and ADV was tested with real time PCR. Among seventy patients with chronic hepatitis B infection, 18 (25.7%) were resistant to LAM and 8 (11.4%) were resistant to ADV. Only one patient was negative for the presence of HBS-Ag (5.6%) and two were negative for HBe-Ag (11.1%). In this study we used a new method (ALLGIO probe assay) that has high sensitivity in detection of adefovir resistance mutants, which we recommend to other researchers. Mutant strains of the YMDD motif of HBV polymerase can be found in some patients under treatment with lamivudine and ADV. ADV has been demonstrated to be efficient in patients with lamivudine resistant HBV.

• Kidney Research and Clinical Practice
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• v.37 no.4
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• pp.323-337
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• 2018

Infectious complications have been considered as a major cause of morbidity and mortality after kidney transplantation, especially in the Asian population. Therefore, prevention, early detection, and prompt treatment of such infections are crucial in kidney transplant recipients. Among all infectious complications, viruses are considered to be the most common agents because of their abundance, infectivity, and latency ability. Herpes simplex virus, varicella zoster virus, Epstein-Barr virus, cytomegalovirus, hepatitis B virus, BK polyomavirus, and adenovirus are well-known etiologic agents of viral infections in kidney transplant patients worldwide because of their wide range of distribution. As DNA viruses, they are able to reactivate after affected patients receive immunosuppressive agents. These DNA viruses can cause systemic diseases or allograft dysfunction, especially in the first six months after transplantation. Pretransplant evaluation and immunization as well as appropriate prophylaxis and preemptive approaches after transplant have been established in the guidelines and are used effectively to reduce the incidence of these viral infections. This review will describe the etiology, diagnosis, prevention, and treatment of viral infections that commonly affect kidney transplant recipients.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.178-178
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• 1994

Hepatitis B Virus (HBV) is a DNA virus with a 3.2kb partially double-stranded genome. The life cycle of the virus involves a reverse transcription of the greater than genome length 3.5kb mRNA. This pegenomic RNA contains all the genetic information encoded by the virus and functions as an intermediate in viral replication. Tumor suppressor p53 has previously been shown to interact with the X-gene product of the HBV, which led us to hypothesize that p53 may act as a negative regulator of HBV replication and the role of the X-gene product is to overcome the p53-mediated restriction. As a first step to prove the above hypothesis, we tested whether p53 represses the propagation of HBV in in vitro replication system. By transient cotransfection of the plasmid containing a complete copy of the HBV genome and/or the plasmid encoding p53, we found that the replication of HBV is specifically blocked by wild-type p53. The levels of HBV DNA, HBs Ag and HBc/e Ag secreted in cell culture media were dramatically reduced upon coexpresion of wild-type p53 but not by the coexpression of the mutants of p53 (G154V and R273L). Furthermore, levels of RNAs originated from HBV genome were repressed more than 10 fold by the cotransfection of the p53 encoding plasmid. These results clearly states that p53 is a nesative regulator of the HBV replication. Next, to addresss the mechanism by which p53 represses the HBV replication, we performed the transient transfection experiments employing the pregenomic/core promoter-CAT(Chloramphenicol Acetyl Transferase) construct as a reporter. Cotransfection of wild-type p53 but not the mutant p53 expression plasmids repressed the CAT activity more than 8 fold. Integrating the above results, we propose that p53 represses the replication of HBV specifically by the down-regulation of the pregenomic/core promoter, which results in the reduced DNA synthesis of HBV. Currently, the mechanism by which HBV overcomes the observed p53-mediated restriction of replication is tinder investigation.

• BMB Reports
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• v.29 no.2
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• pp.156-162
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• 1996

Transcription of hepatitis B viral pregenomic promoter is known to be regulated mainly by the combined interaction of enhancers I, II and the intervening regulatory sequences between the two enhancers. A positive regulatory element was identified by serial deletion and measuring the linked chloramphenicol acetyltransferase (CAT) activities, which overlapped with the 5' region of the X open reading frame. When the positive regulatory element was inserted upstream of the SV40 early promoter, it elevated SV40 promoter activity in HepG2 cells. Two cellular proteins of 110 (p110) and 33 (p33) kDa interacted with the positive element and both of them were present in the nucleus, but p110 also existed in the cytoplasm in phosphorylated form. Dephosphorylation of p110 by acid phosphatase enhanced the DNA-binding activity of p110. The p33 could bind to single-strand DNA specifically as well as to double-strand DNA.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.178-178
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• 1996

Hepatitis B virus (HBV) infection is one of the serious problems in Southeast Asia including Korea because it causes chronic hepatitis, which can easily be transformed In fatal conditions such as cirrhosis and hepatoma. Even though lots of informations on structural characteristics and gene expression mechanisms have been accumulated, the mechanism for HBV-induced hepatocellular injury which is believed to be the consequences of the immunological response is not well understood. In order tn perform immunopathological studies for prevention and treatment of HBV infection, we designed transgenic mice as a disease model which can mimic HBV infection, In this study, a promoter-HBV DNA fragment for the preparation of HBV transgenic mice has been constructed. To add a proper enzyme site on 5' end of HBV gene, total HBV (subtype adr) gene was inserted into BamHI site of pBluescript SK vector and reextracted by PstI-SacI treatment A liver-specific promoter, rat ${\alpha}$ 2u globulin gene promoter, was insrted to pBluescript SK vector and reextracted by BamHI-PstI treatment, Promoter-HBV DNA was constructed by ligation of two fragments using identical PstI sites. For large scale production of promoter-HBV DNA, it was inserted to BamHI-SacI site of pBluescript SK vector.