• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3657-3661
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• 2012

HBV infection is contagious and may be transmitted vertically or horizontally by blood products and body secretions. Over 50% of Iranian carriers have contracted the infection prenatally, making this the most likely route of transmission of HBV in Iran. This study assesses the resistance to Lamivudine in patients with chronic hepatitis B infection using a new ZNA probe Real Time PCR method. To evaluate the effectiveness of Lamivudine therapy for chronic hepatitis B infection, a study was conducted on 70 patients (63 men and 7women), who had received the drug first line. All patients were tested for the presence of HBsAg and HBeAg, the serum ALT level and the HBV DNA load before and after treatment. In all samples resistance to Lamivudine was tested with the ZNA Probe. Our results showed that ZNA Probe Real Time PCR method could detect wild type,YMDD, and its mutants, tyrosine-isoleucine-aspartate-aspartate and tyrosine-valine-aspartate-Aspartate. Among an estimated seventy patients with chronic hepatitis B infection, 18 (25.7%) were resistant to lamivudine. Only one patient was negative for presence of HBS-Ag (5.6%) and two patients were negative for HBe-Ag (11.1%). Real-time PCR with Zip nucleic acid probes is a sensitive, specific and rapid detection method for mutations in the YMDD motif, which will be essential for monitoring patients undergoing Lamivudine antiviral therapy.

• Korean Journal of Clinical Laboratory Science
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• v.45 no.1
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• pp.9-15
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• 2013

Hepatitis B virus (HBV) infection has recently shown to be associated with diabetes mellitus. The objective of this study was to investigate the relationship between chronic hepatitis B and diabetes mellitus indicators. We evaluated anthropometry, metabolic syndrome risk factors, fasting glucose, HbA1c, and C-peptide among the normal and HBV subjects. The partial correlation and average comparison analysis were used to assess the independent association between chronic hepatitis B and diabetes mellitus indicators. Average comparisons of normal and HBV subjects were significantly different in fasting glucose (p<0.000), HbA1c (p<0.000), C-peptide (p<0.000), alanine transaminase (ALT) (p<0.000) and aspartate transaminase (AST) (p<0.000). We may suggest that HBV infection is related to diabetes mellitus indicators such as fasting glucose, HbA1c and C-peptide.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.276-282
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• 1998

Retinoids regulate a wide variety of biological processes such as cellular proliferation and differentiation in many cell types. They have also shown to stimulate replication of several viruses including human cytomegalovirus (CMV). Retinoid signalling pathway involves two distinct subfamilies of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that bind to specific retinoic acid response elements (RAREs) in the promoter regions of retinoid-target genes. Here, we characterized RAREs in the regulatory regions of the CMV and of the hepatitis B vi.us (HBV). The viral RAREs, i.e., CMV-RARE and HBV-RARE, are composed of two consensus RARE half-sites (A/GGGTCA) arranged as a direct repeat separated by 5-bp and 1-bp, respectively. The RAREs were activated by both RAR/RXR heterodimers and RXR homodimers in transient transfection experiments. We also found that COUP-TF$\alpha$ (chicken ovalbumin upstream promoter-transcription factor u) and COUP-TF$\beta$ repressed the retinoid response of the viral elements. Further we demonstrated that previously known retinoid antagonist, SRI 1330, repressed retinoid-induced transactivation of the CMV-RARE. These results implicate Vitamin A, it's nuclear receptors and COUP-TFs as important regulators of the CMV and HBV pathogenesis and the SRl1330 as potential negative modulator of such retinoid-dependent processes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.743-747
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• 2011

Here we describe a case of lamivudine and entecavir resistant chronic hepatitis B, treated with western medicine plus traditional korean medicine combination therapy. We administered Injinchunggan-Tang(茵蔯淸肝湯), a traditional Korean herb remedy, with entecavir to a 45-year-old chronic hepatitis B patient who didn't have achieved HBV-DNA suppression, in spite of 18 month lamivudine mono therapy and 14 month entecavir mono therapy. HBV-DNA decreased more than one thousandth from 98,100 IU/mL to 53 IU/mL just in 23 days, and resultingly it seems that the combination therapy could be very potent, at least to some chronic hepatitis B patients.

• BMB Reports
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• v.54 no.12
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• pp.614-619
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• 2021

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC), which is a highly aggressive cancer. HBV X protein (HBx), one of four HBV gene products, plays pivotal roles in the development and metastasis of HCC. It has been reported that HBx induces liver cancer cell migration and reorganizes actin cytoskeleton, however the molecular basis for actin cytoskeleton reorganization remains obscure. In this study, we for the first time report that HBx promotes actin polymerization and liver cancer cell migration by regulating calcium modulated protein, calmodulin (CaM). HBx physically interacts with CaM to control the level of phosphorylated cofilin, an actin depolymerizing factor. Mechanistically, HBx interacts with CaM, liberates Hsp90 from its inhibitory partner CaM, and increases the activity of Hsp90, thus activating LIMK1/cofilin pathway. Interestingly, the interaction between HBx and CaM is calcium-dependent and requires the CaM binding motif on HBx. These results indicate that HBx modulates CaM which plays a regulatory role in Hsp90/LIMK1/cofilin pathway of actin reorganization, suggesting a new mechanism of HBV-induced HCC metastasis specifically derived by HBx.

• Genomics & Informatics
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• v.6 no.4
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• pp.192-201
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• 2008

Erythropoietin-producing human hepatocellular carcinoma receptor B1 (EPHB1) is a member of the Eph family of receptor tyrosine kinases that mediate vascular system development. Eph receptor overexpression has been observed in various cancers and is related to the malignant transformation, metastasis, and differentiation of cancers, including hepatocellular carcinoma (HCC). Eph receptors regulate cell migration and attachment to the extracellular matrix by modulating integrin activity. EphrinB1, the ligand of EPHB1, has been shown to regulate HCC carcinogenesis. Here, we sought to determine whether EPHB1 polymorphisms are associated with hepatitis B virus (HBV)-infected liver diseases, including chronic liver disease (CLD) and HCC. We genotyped 26 EPHB1 single nucleotide polymorphisms (SNPs) in 399 Korean CLD, HCC, and LD (CLD+HCC) cases and seroconverted controls (HBV clearance, CLE) using the GoldenGate assay. Two SNPs (rs6793828 and rs11717042) and 1 haplotype that were composed of these SNPs were associated with an increased risk for CLD, HCC, and LD (CLD+HCC) compared with CLE. Haplotypes that could be associated with HBV-infected liver diseases by affecting downstream signaling were located in the Eph tyrosine kinase domain of EPHB1. Therefore, we suggest that EPHB1 SNPs, haplotypes, and diplotypes may be genetic markers for the progression of HBV-associated acute hepatitis to CLD and HCC.

• BMB Reports
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• v.42 no.12
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• pp.834-839
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• 2009

DNA methyltransferase (DNMT) 1 is the key enzyme responsible for DNA methylation, which often occurs in CpG islands located near the regulatory regions of genes and affects transcription of specific genes. In this study, we examined the possible association of DNMT1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Seven common polymorphic sites were selected by considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n = 1,100). Statistical analysis demonstrated that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, showed significant association with HBV clearance in a co-dominant model (OR = 1.30, $P^{corr}$ = 0.03) and co- dominant/recessive model (OR = 1.34-1.74, $P^{corr}$ = 0.01-0.03), respectively. These results suggest that two intron polymorphisms of DNMT1, +34542G > C and +38565G > T, might affect HBV clearance.

• Korean Journal of Microbiology
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• v.43 no.1
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• pp.1-6
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• 2007

We describe a multiplex PCR method that can detect and differentiate simultaneously four different kinds of DNA viruses, Epstein-Barr virus (EBV), cytomegalovirus (CMV), hepatitis B virus (HBV) and parvovirus B19 (B19). Primers for the multiplex PCR reaction were designed to amplify specific regions of the EBV (pol), CMV (pol), HBV (pol) and B19 (ns) viral genomes and used to simultaneously detect individual viruses. In order to achieve optimal sensitivity and specificity for multiplex PCR, the thermo-cycling parameters, primer sequences, and concentration of each reaction components were optimized systematically. The sensitivity of the detection method ranged between 5 and 10 copies of viral genome with a mixture of multiple primer pairs. Furthermore, this highly sensitive test showed no cross-reactivity among the four viruses. Thus, the results obtained in this study provide evidence that the assay system is a good tool for supporting the diagnosis of viral infection and contamination.

• BMB Reports
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• v.29 no.2
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• pp.175-179
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• 1996

Viral surface proteins are known to play an essential role in attachment of the virus particle to the host cell membrane. In case of the hepatitis B virus (HBV) several reports have described potential receptors on the target cell side, but no definite receptor protein has been isolated yet. As for the viral side, it has been suggested that the preS region of the envelope protein, especially the preS1 region, is involved in binding of HBV to the host cell. In this study, preS1 region was recombinantly expressed in the form of a maltose binding protein (MBP) fusion protein and used to identify and visualize the expression of putative HBV receptor(s) on the host cell. Using laser scanned confocal microscopy and by FACS analysis, MBP-preS1 proteins were shown to bind to the human hepatoma cell line HepG2 in a receptor-ligand specific manner. The binding kinetic of MBP-preS1 to its cellular receptor was shown to be temperature and time dependent. In cells permeabilized with Triton X-100 and treated with the fusion protein, a specific staining of the nuclear membrane could be observed. To determine the precise location of the receptor binding site within the preS1 region, several short overlapping peptides from this region were synthesized and used in a competition assay. In this way the receptor binding epitope in preS1 was revealed to be amino acid residues 27 to 51, which is in agreement with previous reports. These results confirm the significance of the preS1 region in virus attachment in general, and suggest an internalization pathway mediated by direct attachment of the viral particle to the target cell membrane.

• Journal of Yeungnam Medical Science
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• v.9 no.2
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• pp.407-415
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• 1992

Among 85 patients with anti-HCV positive chronic liver disease, only 21.2% have past history of blood transfusion and over half the cases, they do not have any suspicious risk factors for HCV infection, 3 of 85 families show anti-HCV positive family members. On the other hand, 40 of 60 patients with HBsAg positive chronic liver disease show HBsAg positive family members. In Korea, HBV is transmitted mainly through vertical and intrafamilial infection but HCV disease might be rather horizontal and sporadic than vertical. To define the evident source of infection in sporadic hepatitis C, first of all, simple test with high sensitivity and specificity for diagnosis of HCV infection would be needed.