• Journal of Microbiology and Biotechnology
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• v.10 no.6
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• pp.823-828
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• 2000

The complete nucleotide sequence of hepatitis B virus DNA isolated from Korean patient serum was determined and characterized, and its phylogenetic relation was then investigated. The viral genome was 3,215 base pairs long and included four well known open reading frames (i.e. surface antigens, core antigens, X protein and DNA polymerase). The sequence of the surface antigen showed that the HBV genome under investigation, designated HBV 315, was characteristic of subtype adr. A phylogenetic analysis using the total genome sequence revealed that HBV315 was grouped into genomic group C together with isolates from Japan, China, Thailand, Polynesia, and New Caledonia. The mean percent similarity between HBV315 and other HBV isolates in genomic group C was 97.25%, and that with other genomic groups ranged from 86.16% to 91.25%. The predicted amino acid sequences of HBV315 were compared with two closely related subtype adr isolates, M38636 and D12980. The results showed that the X gene product was identical in the three strains, while there were significant amino acid sequence differences between HBV315 and M38636 in the Pre-S1 and Pre-S2 regions.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.1-10
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• 2005

Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

• Journal of Microbiology and Biotechnology
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• v.27 no.7
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• pp.1336-1344
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• 2017

Hepatitis B virus (HBV) is a major cause of liver cirrhosis and hepatocellular carcinoma. With recent identification of HBV receptor, inhibition of virus entry has become a promising concept in the development of new antiviral drugs. To date, 10 HBV genotypes (A-J) have been defined. We previously generated two murine anti-preS1 monoclonal antibodies (mAbs), KR359 and KR127, that recognize amino acids (aa) 19-26 and 37-45, respectively, in the receptor binding site (aa 13-58, genotype C). Each mAb exhibited virus neutralizing activity in vitro, and a humanized version of KR127 effectively neutralized HBV infection in chimpanzees. In the present study, we constructed a humanized version (HzKR359-1) of KR359 whose antigen binding activity is 4.4-fold higher than that of KR359, as assessed by competitive ELISA, and produced recombinant preS1 antigens (aa 1-60) of different genotypes to investigate the binding capacities of HzKR359-1 and a humanized version (HzKR127-3.2) of KR127 to the 10 HBV genotypes. The results indicate that HzKR359-1 can bind to five genotypes (A, B, C, H, and J), and HzKR127-3.2 can also bind to five genotypes (A, C, D, G, and I). The combination of these two antibodies can bind to eight genotypes (A-D, G-J), and to genotype C additively. Considering that genotypes A-D are common, whereas genotypes E and F are occasionally represented in small patient population, the combination of these two antibodies might block the entry of most virus genotypes and thus broadly neutralize HBV infection.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.7 no.2
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• pp.197-207
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• 2004

Purpose: To evaluate the long-term therapeutic efficacy and durability of lamivudine in Korean children with chronic hepatitis B. Methods: A total of 48 children (31 male and 17 female; age, 1~18 years, mean, 8 years) with chronic hepatitis B who received lamivudine for at least six months from March 1999 to September 2004 were followed for a mean period of 29 months (8~66 months) at Department of Pediatrics, Kyungpook National University Hospital in Korea. Response to treatment was defined as the normalization of ALT and HBV DNA levels, and HBeAg seroconversion after the initiation of treatment. Results: Twenty nine (60%) among the 48 children treated with lamivudine responded and nine (19%) children lost HBsAg during therapy. ALT and HBV DNA level had normalized in 94% one year after the initiation of treatment. Kaplan-Meier estimates of cumulative HBeAg seroconversion rates over the years were 13% (0.5 year), 34% (1 year), 50% (1.5 years), 68% (2 years), 79% (2.5 years) and 90% at 3 years respectively. Above all, among the 22 children treated before the age of seven, loss of HBsAg occurred in eight (36%), which showed superior rate of HBsAg loss (p=0.002 vs age >7). Conclusion: Long-term treatment of lamivudine improved the rate of HBeAg seroconversion in Korean children with chronic hepatitis B. After three years' observation, most of treated children have sustained HBeAg clearance. We believe that lamivudine should be tried as the first therapeutic option for children with chronic hepatitis B in immune clearance phase.

• Clinical and Experimental Pediatrics
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• v.48 no.1
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• pp.55-62
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• 2005

Purpose : We compared the therapeutic efficacy of lamivudine and alpha-interferon in children with chronic hepatitis B two years after the initiation of treatment, so that we could verify the safety and long term efficacy of lamivudine in children. Methods : We prospectively studied 44 children(32 male and 12 female; age, 1-18 years, mean, 9 years) treated for chronic hepatitis B from September 1996 to June 2004 in Kyungpook National University Hospital in Korea. Twenty three children were treated with interferon, and 21 with lamivudine. Treatment efficacy was defined as the normalization of ALT and hepatitis B virus(HBV) DNA levels, loss of HBsAg and HBeAg seroconversion at two years after the initiation of treatment. Results : Among the 23 children treated with interferon, the ALT level normalized in 10 children(43 %) and HBV DNA was undetectable in 12 children(52%). HBsAg was undetectable in one child (4 %) and HBeAg seroconversion occurred in nine children(39%) two years after the initiation of treatment. In comparison, among the 21 children treated with lamivudine, ALT normalized in 20 children (95%), HBV DNA in 19(90%), HBsAg in 5(24%), and HBeAg seroconversion occurred in 13(62%). Above all, in the lamivudine treated group under the age of seven, HBeAg and HBsAg seroconversion occurred in six(75%) and five(63%) out of the eight children respectively, which showed superior HBsAg seroconversion rate if treated in preschool aged children. Conclusion : We believe that the therapeutic efficacy of lamivudine in children with chronic hepatitis B could be better than interferon with fewer side effects, especially in preschool aged children.

• Clinical and Molecular Hepatology
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• v.24 no.4
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• pp.384-391
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• 2018

Backgrounds/Aims: The objective of our study was to determine the epidemiological, laboratory, and serological characteristics of patients with chronic hepatitis B virus (HBV) infection and normal transaminases. The study also aimed to evaluate liver damage by measuring the liver fibrosis (LF) grade and to identify possible factors associated with the presence of fibrosis. Methods: A retrospective observational study was conducted in patients with chronic HBV infection and classified as inactive carriers or immune-tolerant. Epidemiological variables of age, sex, immigrant, alcohol consumption, and body mass index (BMI), as well as virological variables (HBV DNA) and transaminase level were collected throughout the follow-up. The LF grade was evaluated by transient elastography. The cutoff value for significant fibrosis (SF) was liver stiffness ${\geq}7.9kPa$. Results: A total of 214 patients were included in the analysis, and 62% of them had a BMI ${\geq}25kg/m^2$. During follow-up, 4% of patients showed transaminase elevation (<1.5 times normal). Most patients had a viral DNA level <2,000 IU/mL (83%). Data on LF were available in 160 patients; of these, 14% had SF, 9% F3, and 6% F4. The variables associated with the presence of SF were transaminase alteration during follow-up, as 23% of patients with SF had elevated transaminases versus 3% of patients without SF (P<0.005), and BMI, as the vast majority of patients with SF (88%) had a BMI ${\geq}25kg/m^2$ versus 56% of patients without SF (P<0.05). Conclusions: In patients with chronic HBV infection and normal transaminases, liver damage does not seem to be related to DNA levels, alcohol consumption, or immigrant status. SF seems to be associated with transaminase alteration during follow-up and elevated BMI. It is therefore recommended to measure LF grade with validated non-invasive methods in such patients.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.1
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• pp.23-29
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• 2009

Purpose: To provide the primary data for reaching a consensus on the adequate duration of treatment of lamivudine in children with HBeAg negative chronic hepatitis B. Methods: Seven of 83 children/adolescents with chronic hepatitis B were diagnosed with HBeAg-negative and HBV DNA-positive chronic hepatitis B and treated with lamivudine. Six children/adolescents were enrolled among 7 patients, who had been treated with lamivudine over 2 years. The primary goal of treatment was HBV DNA clearance and normalization of the serum ALT level; the final goal of treatment was the durability of the complete response after discontinuation of lamivudine. It was planned to continue lamivudine for more than two additional years after HBV DNA negativity and normalization of ALT. Results: The mean duration of lamivudine treatment was 32.2 months (range, 26~40 months) and the mean duration of follow-up was 59.5 months (range, 26~110 months). HBV DNA levels became undetectable (<0.5 pg/mL) in 6 patients within 3 months of treatment. ALT levels were normalized in 3.5 months (range, 2~7 months) in all 6 patients. Biochemical breakthrough developed in 1 patient 18 months after the initiation of lamivudine treatment. No evidence of relapse could be found in 4 patients with a mean follow-up of 23.8 months (range, 4~75 months) after cessation of lamivudine treatment. Conclusion: Suppression of HBV replication and normalization of serum ALT levels were effectively achieved with long-term lamivudine treatment in children/adolescents with HBeAg-negative chronic hepatitis B. Two additional years of lamivudine may be needed after HBV DNA clearance and ALT normalization in HBeAg-negative chronic hepatitis B in order to decrease the relapse rate.

• Korean Journal of Microbiology
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• v.27 no.3
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• pp.169-175
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• 1989

To study the role of mutant precore region in expression and secretion of hapatitis B viral core antigen, we have cloned core antigen gene(HBc) with or without precore region in geterologous expression vectors containing SV40 promoter, yeast promoter, and lambda $P_{L}$ promoter. In COS cells transfected with plasmid containing C-gene with precore region, antigens were detected in both cell extract and cultured medium. However, in the cells transfected with plasmids containing C-gene without precore or with mutated precore region by one nucleotide (T) addition at the nucleotide 1,821, HBcAg was detected only in cell extracts. These results support that the mutation by one nucleotide addition shifted the initiation codon of precore region to 53 nucleotides upward and the elongated precore region also played a major role in the secretion of HBcAg in mammalian cells. In the case of yeast and E. coli, HBcAg was detected only in cell extracts in spite of the presence of precore region, which suggest that precore region could not affect HBcAg secretion in these system.

• 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.