• Korean Journal of Microbiology
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• v.28 no.1
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• pp.1-5
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• 1990

The coding sequence of hepatitis B viral core antigen (HBcAg) (subtype adr) contains two in-phase initiation codons, one for precore and the other for core antigen gene. To study the expression of core antigen and the role of precore region, the coding sequence of HBcAg with or without precore (pre-C) region were subcloned into yeast expression vector containing phosphoglycerate kinase (PGK) promoter. To study the role of upstream region in the expression of the core antigen, a series of 5' deletion mutants were also subcloned into the vector. After transformation into various host strains, the expression of HBcAg were analysed by radio-immunoassat. Under optimal condition of core antigen gene expression in yeast, the highest amount of antigen was detected in the cell line SHY4 containing pGKHBc plasmid composed of the yeast PGK gene promoter, terminator and C-gene. Regardless of the presence of precore region, core antigen was not detected in the medium but in cell extract. These results suggest that precore region cannot affect the secretion of core antigen in Saccharomyces cerevisiae.

• Korean Journal of Psychosomatic Medicine
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• v.6 no.1
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• pp.35-45
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• 1998

Objectives : The purpose of this study was to determine correlation between coping strategies to disease and quality of life in chrome viral B hepatitis patients ; to investigate difference of coping strategies to disease and quality in life between chronic viral B hepatitis patients and normal persons ; and to identify major variables related to quality in life of chronic viral B hepatitis patients. Methods: The authors used Weisman coping strategy scale for measuring coping ability and efficacies, and the questionnaire for measuring quality of life including physical, psychological, social and economical aspects and satisfaction of sexual life was made by authors based on related literatures. Data were collected through questionnaire survey over a period from Sep 15, 1994 to Nov 11, 1994. Subjects served for this study consisted of 94 chronic viral B hepatitis patients visited to department of internal medicine at one general hospital and 100 normal persons visited to one general hospital for routine check up of health. The collected data were analyzed by SAS and the statistical methods for analysis were Chisquare, t-test and multiple regression analysis. Results : 1) It was revealed that coping strategies to disease significantly correlated to individual's quality of life. 2) There was no significant difference in coping strategies to disease between chronic viral B hepatitis patients and normal persons. However, chronic viral B hepatitis patients showed the lower scroes of quality of life in physical, psychological and economical aspects. 3) The most important variables which were influenced upon quality of life were coping strategies to disease and satisfaction of sexual life. That is, the more active coping strategies to diseases and the higher satisfaction of sexual life, consequently the higher quality of life was. Especially male patient group or normal persons showed each other the higher scores of quality of life in physical and psychological area than female group or patient group. 4) No statistically significant difference in coping strategies to disease and quality of life was found between HBeAg positive group and HBeAg negative group. Conclusions : The authors suggest that chronic viral B hepatitis patients may show the lower score of quality of life than normal person. Therefore, quality of life assessment should become an integral part of all clinical area that seek to assess the effectiveness of treatment. Also, through the interdisciplinary approach, a comprehensive paradigm that can better account for the effects of chronic disease on the individual' s quality of life should be developed.

• Journal of Preventive Medicine and Public Health
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• v.35 no.2
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• pp.129-135
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• 2002

Objective : The primary objective of this study was to estimate the prevalence of HBsAg-positives in the late 1990's among Korean adults. In addition, we evaluated the association of age, a residential area, a vaccination rate, a family history of chronic liver diseases and a past history of acute liver disease with the seropositivity of HBsAg, and estimated the prevalence of chronic HBV infection by follow-up for 6 month or more. Methods : A total of 10 areas, six metropolitan and four small cities, were selected. In each cities, one health screening center was selected for recruitment of study subjects. The study subjects were enrolled from a general health examination program that is provided by medical insurance companies. Questionnaires on various risk factors were administered to the study subjects. Sera was drawn and tested for HBsAg by radioimmunoassay. HBeAg and ALT were also tested for those of HBsAg positive. The HBsAg positives was retest for HBsAg 6 months later Results : Among the study subjects (n= 1816), the seroprevalence of HBsAg was 5.5% (95% CI=4.5%-6.6%), 7.4% in men (95% CI=5.8-9.4) and 3.6% in women (95% CI=2.5-5.0). A past history of acute liver disease and a family history of chronic liver diseases was shown to be risk factors for HBsAg positivity. Among the 31 HBsAg-positives, negative seroconversion rate was estimated to be 3.2%, Thus, prevalence of chronic HBV infection was estimated to be 5.3% (95% CI=3.7-6.6). Conclusion : In this study, the HBsAg seroprevalence rate was lower than that of the other studies in 1980's, particularly in young adult and women. Considering the public health importance of liver cancer and chronic liver diseases, the further effort is needed to prevent and reduce the HBV infection.

• YAKHAK HOEJI
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• v.54 no.4
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• pp.316-321
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• 2010

Adefovir dipivoxil which was originally developed by Gilead Sciences has been used as treatments of HIV and HBV, especially a therapeutics for HBeAg positive and negative chronic patients. We developed highly efficient purification method using reverse phase column chromatography for mass production and a stable amorphous Adefovir dipivoxil using solid dispersion method. Reverse phase column chromatography led to highly pure product, more than 99.7% by HPLC and can be used for mass production compared with normal column chromatography. Solid dispersion method containing watersoluble polymer and Isomalt showed improved stability of amorphous Adefovir dipivoxil against heat and moisture.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1043-1047
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• 2013

Although there have been many studies investigating possible associations between the C1653T mutation and risk of HCC, the results have been inconsistent. We conducted searches of the published literature in Pubmed and Embase databases up to January 2013. Seventeen studies with a total of 1,085 HCC cases and 1,365 healthy controls were retrieved. We found a significant association between the C1653T mutation and HCC risk (OR = 2.01, 95%CI= 1.49-2.70). In the subgroup analysis by ethnicity, a significant association was also found in Asians (OR = 2.07, 95%CI= 1.71-2.51). In subgroup analysis by HBV genotype, B and C were linked with development of HCC (B:OR = 2.21, 95%CI= 1.13-4.34; C:OR = 2.26, 95%CI= 1.61-3.16). However, no significant association was found between the C1653T mutation and HCC risk in HBeAg positive cases. In conclusion, this meta-analysis suggests that the C1653T mutation may be associated with susceptibility to HCC.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6227-6231
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• 2013

In the past, hepatitis B virus (HBV) infection was endemic in the general Korean population. The association of HBV infection with the occurrence of liver cancer has been well demonstrated in several epidemiologic studies. While the mortality rates of liver cancer in Korea have decreased steadily over the last decade, the presence of hepatitis B surface antigen (HBsAg) in mothers remains high at 3-4%, and 25.5% of these HBsAg positive mothers are positive for hepatitis B e antigen (HBeAg). HBV infection caused almost a quarter of hepatocellular carcinoma (HCC) cases and one-third of deaths from HCC. These aspects of HBV infection prompted the Korean government to create a vaccination program against HBV in the early 1980s. In 1995, the Communicable Disease Prevention Act (CDPA) was reformed, and the government increased the number of HBV vaccines in the National Immunization Program (NIP), driving the vaccination rate up to 95%. In 2000, the National Health Insurance Act (NHIA) was enacted, which provided increased resources for the prevention of perinatal HBV infection. Then in 2002, the Korean government, in conjunction with the Korean Medical Association (KMA), launched an HBV perinatal transmission prevention program. The prevalence of HBsAg in children had been high (4-5%) in the early 1980s, but had dropped to below 1% in 1995, and finally reached 0.2% in 2006 after the NIP had been implemented. After the success of the NIP, Korea finally obtained its first certification of achievement from the Western Pacific Regional Office of the World Health Organization (WPRO-WHO) for reaching its goal for HBV control. An age-period-cohort analysis showed a significant reduction in the liver cancer mortality rate in children and adolescents after the NIP had been implemented. In addition to its vaccination efforts, Korea launched the National Cancer Screening Program (NCSP) for 5 leading sites of cancer, including the liver, in 1999. As a consequence of this program, the 5-year liver cancer survival rate increased from 13.2% (1996-2000) to 23.3% (2003-2008). The development of both the primary and secondary prevention for liver cancer including HBV immunization and cancer screening has been of critical importance.

• Journal of Microbiology and Biotechnology
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• v.17 no.4
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• pp.701-704
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• 2007

This report describes the full-length sequences of 2HBV clones from a hepatocellular carcinoma (HCC) patient, one with preC mutation (1896A) and the other without preC mutation. The high level of discrepancy in mutation frequency between these 2 strains was observed in the Core (C) region among 4 ORFs. These data support previous results that Korean HBV strains, belonging to genotype C2, are prone to mutations. It is possible that the mutations (BCP and preC mutations) associated with the HBeAg defective production might contribute to the diversity of mutations related to HBV persistence, playing an important role in hepatocarcinogenesis in this patient.

• Archives of Pharmacal Research
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• v.29 no.5
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• pp.405-411
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• 2006

Biphenyl dimethyl dicarboxylate (DDB) is a hepatoprotectant, which is used as an adjuvant agent in a treatment for chronic hepatitis. Amantadine is an antiviral agent, which is utilized primarily in the treatment of influenza, but also, occasionally in the treatment of hepatitis C. In a previous study, we reported that DDB, coupled with amantadine, would exert an anti-HBV effect, via the induction of interferon-inducible gene expression in the HepG2 2.2.15 cell line. The primary objective of the present study was to determine whether or not DDB and/or amantadine exhibit anti-HBV properties, and what mechanisms of action might be involved in such properties. In our study, we were able to determine that DDB stimulates Jak/Stat signaling, and induces the expression of interferon alpha $(IFN-\alpha)$ stimulated genes, most notably 6-16 and ISG12. In addition, the antiviral effectors induced by $IFN-\alpha$, PKR, OAS, and MxA, were regulated in the presence of DDB at its optimal concentration $(250{\mu}g/mL)$, to a degree commensurate with the degree of induction associated with the $IFN-\alpha$ treated group. Finally, we determined that the replication of pregenomic RNA and HBeAg was inhibited by DDB treatment, and this inhibition was maximized when coupled with the administration of amantadine $(25{\mu}g/mL)$. In conclusion, the results of this study demonstrated clearly that DDB, as well as the combination of DDB/amantadine, directly inhibited $IFN-\alpha$ signaling-mediated replication of HBV in infected hepatocytes, and thus may represent a novel treatment for chronic hepatitis B, which would be characterized principally by its improved safety over other treatment strategies.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.217-223
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• 2013

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the outcomes for patients are still poor. It is important to determine the original type of synchronous multinodular HCC for preoperative assessment and the choice of treatment therapy as well as for the prediction of prognosis after treatment. Aims: To analyze clinicopathologic characteristics and prognoses in patients with multicentric occurrence (MO) and intrahepatic metastasis (IM) of synchronous multinodular hepatocellular carcinoma (HCC). Methods: The study group comprised 42 multinodular HCC patients with a total of 112 nodules. The control group comprised 20 HCC patients with 16 single nodular HCC cases and 4 HCC cases with a portal vein tumor emboli. The mitochondrial DNA (mtDNA) D-loop region was sequenced, and the patients of the study group were categorized as MO or IM based on the sequence variations. Univariate and multivariate analyses were used to determine the important clinicopathologic characteristics in the two groups. Results: In the study group, 20 cases were categorized as MO, and 22 as IM, whereas all 20 cases in the control group were characterized as IM. Several factors significantly differed between the IM and MO patients, including hepatitis B e antigen (HBeAg), cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and the histological grade of the primary nodule. Multivariate analysis further demonstrated that cirrhosis and portal vein and/or microvascular tumor thrombus were independent factors differentiating between IM and MO patients. The tumor-free survival time of the MO subjects was significantly longer than that of the IM subjects ($25.7{\pm}4.8$ months vs. $8.9{\pm}3.1$ months, p=0.017). Similarly, the overall survival time of the MO subjects was longer ($31.6{\pm}5.3$ months vs. $15.4{\pm}3.4$ months, p=0.024). The multivariate analysis further demonstrated that the original type (p=0.035) and Child-Pugh grade (p<0.001) were independent predictors of tumor-free survival time. Cirrhosis (p=0.011), original type (p=0.034) and Child-Pugh grade (p<0.001) were independent predictors of overall survival time. Conclusions: HBeAg, cumulative tumor size, tumor nodule location, cirrhosis, portal vein and/or microvascular tumor embolus and histological grade of the primary nodule are important factors for differentiating IM and MO. MO HCC patients might have a favorable outcome compared with IM patients.

• Tuberculosis and Respiratory Diseases
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• v.61 no.5
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• pp.440-446
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• 2006

Background: Post-transplant tuberculosis (TB) is a serious complication in solid organ transplant recipients worldwide, However there is little or no data on TB in liver or heart transplant recipients in Korea. Methods: The incidence and clinical characteristics of TB of 730 patients who had undergone a liver transplant in a university hospital in Korea between 1992 and 2004, and 110 heart transplant recipients in the same period, were reviewed retrospectively. Results: The incidence of TB was 1.5%(11/730) and 2.7%(3/110) in the liver and heart transplantation, respectively. The median time from the transplant to the development of TB was 8.4 months(1.0-30.8). and the mean time from the symptoms to the diagnosis of TB was $2.1{\pm}3.6$ months(0.3-13.2). Nine patients (65%) had pulmonary TB and five (35%) had extrapulmonary TB. The leukopenia and positive HbeAg at the baseline, post-transplant diabetes mellitus, and chronic rejection were associated with the development of TB in the liver transplant recipients. Ten patients were treated with a 4-drug standard regimen for a mean duration of $7.8{\pm}3.5$ months. One patients died of TB. Conclusion: The incidence of TB in liver or heart transplant recipients was similar to that reported in other countries with a similar TB-burden.