• 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.

• Journal of Microbiology and Biotechnology
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• v.18 no.10
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• pp.1722-1728
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• 2008

The natural course of chronic hepatitis B (CH-B) virus infection is reportedly variable, and the long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B infection are distinct from HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in the south Indian setting remain largely unclear. We prospectively studied 679 consecutive patients for HBsAg, HBeAg, anti-HBe, and HBV DNA by qualitative PCR. Randomly selected samples were subjected to bidirectional sequencing to reveal core/precore variants. Of the total 679 chronic HBV cases investigated, 23% (154/679) were replicative HBV carriers. Furthermore, amongst the 560 HBV DNA samples analyzed, 26% (146/560) were viremic. Among the 154 HBeAg positive cases, HBV DNA was positive in 118 cases (77%), significantly (p<0.001) higher than the anti-HBe positive (7%) (28/406) cases. Significant increase in liver disease (p<0.01) with ALT enzyme elevation (p<0.001) was observed in both HBe and anti-HBe viremic cases. Interestingly, low frequencies of mutations were seen in the precore region of the HBV strains studied. HBV precore and core promoter variants were less often detected in subjects with "e" negative chronic HBV infection and, therefore, may not have a prognostic role in determining liver disease sequelae in this part of tropical India.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.1 no.1
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• pp.79-89
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• 1998

Purpose: Though many antiviral or immunomodulatory agents have been used in patients with chronic HBV hepatitis, interferon is considered to be the only effective therapeutic agent so far. Among immunomodulatory agents, thymodulin, the oral form of thymosin, is currently in clinical trial. We compared the efficacy of alfa-interferon therapy alone with a combined therapy of alfa-interferon and thymodulin in children with chronic active hepatitis B. Method: Twenty three children aged 4.4~13.7 years who were known to be positive for HBsAg and HBeAg in serum for at least 6 months and who had biopsy-proven chronic active hepatitis were given either combined therapy of alfa-interferon and thymodulin or alfa-interferon alone, and all children were HBV DNA positive in their serum at the beginning. Follow-ups have been done for at least 1 year after a 6 month course of therapy and clearance of viral replication markers has been evaluated. Results: 1) During follow up period, 11 (48%) children were seroconverted to anti-HBe and were cleared of HBV DNA from their serum. However, 2 of them relapsed after discontinuance of interferon therapy. 2) Seroconversion occurred more frequently among those who had not been vertically transmitted, had elevated serum ALT levels and low HBV DNA levels before interferon therapy. 3) There was no significant advantage of the combined therapy with thymodulin compared to interferon therapy alone. Conclusion: Combined therapy of alfa-interferon and thymodulin failed to demonstrate synergistic effect. We think that combination therapies of alfa-interferon with other antiviral or immunomodulatory agents need to be studied in order to achieve better therapeutic responses.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.80.2-80.2
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• 2003

The nucleoside analogue, L-FMAUS was synthesized from L-FMAU which has been shown to have significant antiviral acitivity against hepatitis B virus (HBV). The anti-HBV activity and toxicity of the L-FMAUS were examined by a cell culture system using a hepatitis B virus (HBV) producing cell line, HepG2 2.2.15. L-FMAUS was assayed for the inhibition of HBV multiplication by measurement of HBV DNA and surface antigen (HBsAg) levels in the extracellular medium of HepG2 2.2.15 cells after an 8-day treatment. (omitted)

• BMB Reports
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• v.30 no.4
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• pp.269-273
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• 1997

Heptocvte-specific expression induced by Hepatitis B virus (HBV) enhancer 2-core gene promoter was examined in various hepatocyte and non-hepatocyte cell lines. using non-viral and retroviral vector systems in which chloramphenicol acetyltransferase (CAT) is used as a reporter. The non-viral plasmid containing the HBV enhancer 2-core promoter exhibited 22 and 66% of CAT activities in hepatoma cell lines. HepG2 and Hep3B, respectively when compared with CAT activity expressed by CMV promoter. The CAT activities, however. were found to be marginal in other tested hepatoma cell lines as well as mouse primary hepatocytes and non-hepatocytes. The HBV enhancer 2 located upstream the CMV promoter did not affect the CMV promoter activity nor provided hepatocyte-specific expression. Transfection of retroviral plasmid DNA containing the HBV enhancer 2-core promoter as an internal promoter exhibited high and specific CAT expression in HepG2 and Hep3B cell lines but the activity value was 5 to 10 fold lower than the non-viral plasmid with identical promoter. These results suggest that the usage of HBV enhancer 2-core promoter for liver specific expression is limited to certain vectors and hepatocyte cell lines.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1411-1414
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• 2014

Background: Hepatitis B and C are the leading causes of liver diseases worldwide. For hematological and solid malignancy patients undergoing chemotherapy, increases in HBV DNA and HCV RNA levels can be detected which may result in reactivation and hepatitis-related morbidity and mortality. The aim of this study was to determine the seroprevalence of Hbs ag and Anti HCV positivity in patients with solid malignancies undergoing chemotherapy and consequences during follow-up. Materials and Methods: The files of 914 patients with solid malignancies whose hepatitis markers were determined serologically at diagnosis were reviewed retrospectively. All underwent adjuvant/palliative chemotherapy. For the cases with HBV and/or HCV positivity, HBV DNA and HCV RNA levels, liver function tests at diagnosis and during follow-up and the treatment modalities that were chosen were determined. Results: Of 914 cases, Hbs Ag, anti Hbs and anti HCV positivity were detected in 40 (4.4%), 336 (36.8%) and 26 (2.8%) of the cases respectively. All of the Hbs ag positive patients received prophylactic lamuvidine before the start of chemotherapy. In the Hbs ag and anti HCV positive cases, liver failure was not detected during chemotherapy and a delay in chemotherapy courses because of hepatitis was not encountered. Conclusions: Just as with hematological malignancies, screening for HBV and HCV should also be considered for patients with solid tumors undergoing chemotherapy. Prophylactic antiviral therapy for HBV reduces both the reactivation rates and HBV related mortality and morbidity. The clinical impact of HCV infection on patients undergoing chemotherapy is still not well characterized.

• The Journal of Korean Medicine
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• v.19 no.2
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• pp.244-270
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• 1998

This study was performed to investigate an anti-HBV activities of the aqueous extracts from 10 Korean herbal medicines in the HepG2 2.2.15 cell culture system and the results were as follows: 1. The extracts of 6 plants (Herba Artemisiae Capillaris, Radix et Rhizoma Rhei, Cortex Cinnamomi, Fructus Chebulae, Fructus Rubi and Radix Rubi) decreased, significantly and dose-dependently, the levels of extracellular HBV virion in the concentrations (10, 100, 500 and $1,000\;{\mu}g/m{\ell}$) tested. 2. However, others (Radix lsatidis, Lignum Sappan, Herba Lysimachiae and Fructus Lycii) did not show any effect either on the replication of HBV or on the levels of virion DNA in the culture media of HepG2 2.2.15 cell. 3. Among the 6 plants which showed the inhibitory potency on the production of extracellular HBV virion, Radix et Rhizoma Rhei, Cortex Cinnamomi, Fructus Chebulae, Fructus Rubi and Radix Rubi except Herba Artemisiae Capillaris also showed the inhibition of the replication of intracellular HEV DNA in the range of $100{\sim}500\;{\mu}g/m{\ell}$. Considering the above results, it is thought that 6 plants(Herba Artemisiae Capillaris, Radix et Rhizoma Rhei, Cortex Cinnamomi, Fructus Chebulae, Fructus Rubi and Radix Rubi) possess the anti-HBV activities in the HepG2 2.2.15 cell culture system. We thus suggest that these plants possess a potential as a therapeutic agent for the chronic viral hepatitis. These results might be useful as a basic data for the development of the new preventive drugs for HBV diseases.

• Microbiology and Biotechnology Letters
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• v.14 no.6
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• pp.455-460
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• 1986

Dane particle was prepared from the plasma of chronic HBsAg carrier with high levels of HBsAg activity. DNA extracted front Dane particle core after a DNA polymerase reaction with $\alpha$-($^{32}$P) dNTP, was identified as HBV DNA by liquid scintillation counter and agarose gel electrophoresis-G.M. counting. To produce Hepatitis B surface antigen for use as a vaccine against Hepatitis B virus infection, yeast strains harboring recombinant plasmid with Apase promoter was used. Recombinant plasmid was construced from pHBV 130 and pAN 82, transformed into E coli, and then transferred into yeast strains. HBsAg was produced by derepression in Burkholder minimal medium with controlled inorganic phosphate concentration. The kinetics of HBsAg production was also investigated. Total HBsAg activity increased rapidly between 3 and 6 hours after transfer to phosphate-free medium and reached a maximum at around 9th hour. The transfer into phosphate-free medium after 6 hours in high phosphate cell growth medium gave maximum activity.

• Clinical and Molecular Hepatology
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• v.24 no.4
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• pp.374-383
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• 2018

Background/Aims: There have been numerous efforts to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during pregnancy. However, there are limited data regarding the outcomes of pregnant women after delivery. This study was performed to evaluate the efficacy of antiviral agents in preventing MTCT of HBV and maternal long-term outcomes. Methods: The HBV-infected pregnant women treated with antiviral agents to prevent MTCT were retrospectively reviewed. Forty-one pregnant women who received telbivudine or tenofovir during late pregnancy (28-34 week) were analyzed. Hepatitis B virus surface antibody (HBsAb) positivity was tested in 43 infants after 7 months of birth. Eleven mothers were followed >1 year after delivery. Results: The mean HBV DNA titer before antiviral therapy was 8.67 (6.60-9.49) log copies/mL, and the median age at delivery was 32 years (range, 22-40). Eleven patients were treated with tenofovir and 30 with telbivudine. The median duration was 57 days (range, 23-100), and the median HBV DNA titer at birth was 5.06 log copies/mL (range, 2.06-6.50). Antiviral treatments were associated with significant HBV DNA reduction (P<0.001). Among 43 infants (two cases of twins), HBsAb was not detected in two, subsequently confirmed to have HBV infection. Biochemical flare was observed in two of 11 mothers followed >12 months, and an antiviral agent was administered. Conclusions: Antiviral treatment during late pregnancy effectively reduced MTCT. Long-term follow-up should be required in such cases. In addition, given that maternal biochemical flare occurred in 18% of mothers, re-administration of antiviral agents might be required.

• 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.