• Journal of Microbiology and Biotechnology
• /
• v.28 no.8
• /
• pp.1376-1383
• /
• 2018

The hepatitis B virus (HBV) envelope contains small (S), middle (M), and large (L) proteins. PreS1 of the L protein contains a receptor-binding motif crucial for HBV infection. This motif is highly conserved among 10 HBV genotypes (A-J), making it a potential target for the prevention of HBV infection. In this study, we successfully generated a neutralizing human monoclonal antibody (mAb), 1A8 (IgG1), that recognizes the receptor-binding motif of preS1 using a phage-displayed human synthetic Fab library. Analysis of the antigen-binding activity of 1A8 for different genotypes indicated that it can specifically bind to the preS1 of major HBV genotypes (A-D). Based on Bio-Layer interferometry, the affinity ($K_D$) of 1A8 for the preS1 of genotype C was 3.55 nM. 1A8 immunoprecipitated the hepatitis B virions of genotypes C and D. In an in vitro neutralization assay using HepG2 cells overexpressing the cellular receptor sodium taurocholate cotransporting polypeptide, 1A8 effectively neutralized HBV infection with genotype D. Taken together, the results suggest that 1A8 may neutralize the four HBV genotypes. Considering that genotypes A-D are most prevalent, 1A8 may be a neutralizing human mAb with promising potential in the prevention and treatment of HBV infection.

• Journal of Preventive Medicine and Public Health
• /
• v.55 no.3
• /
• pp.263-272
• /
• 2022

Objectives: Infections with hepatitis B, C, and D virus (HBV, HCV, and HDV) are a major public health problem and lead to serious complications such as cirrhosis and hepatocellular carcinoma. We aimed to determine the seroprevalence of hepatitis B surface antigen (HBsAg), anti-HCV, anti-HDV immunoglobulin G, alpha-fetoprotein (AFP), and dual and triple hepatitis virus infections in Mongolia. Methods: A total of 2313 participants from urban and rural regions were randomly recruited for this cross-sectional study. A questionnaire was used to identify the risk factors for hepatitis virus infections, and the seromarkers were measured using immunoassay kits. Results: Among all participants, the prevalence of HBV, HCV, and HDV was 15.6%, 36.6%, and 14.3%, respectively. The infection rates were significantly higher in females and participants with a lower education level, rural residence, older age, and a history of blood transfusion. HBV and HCV co-infection was found in 120 (5.2%) participants and HBV, HCV, and HDV triple infection was detected in 67 (2.9%) participants. The prevalence of elevated AFP was 2.7%, 5.5%, and 2.6% higher in participants who were seropositive for HBsAg (p=0.01), anti-HCV (p<0.001), and anti-HDV (p=0.022), respectively. Elevated AFP was more prevalent in participants co-infected with HBV and HCV (5.8%, p=0.023), HBV and HDV (6.0%, p<0.001), and triple-infected with HBV, HCV, and HDV (7.5%) than in uninfected individuals. Conclusions: Nearly half (49.8%) of the study population aged ≥40 years were infected with HBV, HCV, or HDV, and 22.4% had dual or triple infections.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.2 no.2
• /
• pp.169-177
• /
• 1999

Purpose: To evaluate the efficacy of interferon alpha therapy with or without prednisolone in children with chronic hepatitis B. Methods: Twenty-eight children (22 boys, 6 girls, mean age 130 months) had seropositive results for HBsAg, HBeAg and HBV DNA; 11 had chronic persistent hepatitis and 17 had chronic active hepatitis. The patients were divided into two groups depending upon their inflammatory activity on liver biopsy, pretreatment serum ALT levels and HBV DNA levels. Fourteen children (group 1: chronic active hepatitis, ALT ${\geq}$ 100 IU/L and HBV DNA ${\leq}$ 100 pg/$300\;{\mu}L$) received interferon alpha 2a 5 $MU/m^2$ of body surface three times weekly for 6 months. Fourteen children (group 2: chronic persistent hepatitis or chronic active hepatitis with ALT < 100 IU/L or HBV DNA > 100 pg/$300\;{\mu}L$) received prednisolone in decreasing daily doses of 60 mg/$m^2$, 40 mg/$m^2$, and 20 mg/$m^2$, each for 2 weeks, followed after 2 weeks by interferon alpha 2a on the same schedule. At the end of therapy, 3 end points were analyzed: HBeAg seroconversion, serum ALT normalization rate and clearance of serum HBV DNA. Results: At the end of treatment, HBe antigen-to antibody seroconversion was higher but not more significant in group 1 than group 2 (71.4% vs. 50.0%). Only one patient in group 2 who lost HBeAg, also cleared HBsAg. ALT normalization was similar in both groups (64.3% in group 1 vs. 55.6% in group 2). Clearance of serum HBV DNA was observed in 78.6% of patients in group 1 and 64.3% in group 2, but no significant differences. Complete response was similarly achieved in both groups (57.1% in group 1 vs. 50.0% in group 2). Interferon alpha therapy with prednisolone priming was well tolerated and all children finished therapy. Conclusion: The combined therapy with prednisolone followed by interferon alpha may be safe and effective in inducing a serological and biochemical remission of the disease in approximately 50% of children with chronic hepatitis B and with a high level of viral replication and less active disease. However, a controlled study should be performed to confirm these results.

• Pediatric Infection and Vaccine
• /
• v.11 no.1
• /
• pp.73-80
• /
• 2004

Purpose : The serial clinical findings, biochemical results, and serological hepatitis B virus(HBV) markers in Korean children with chronic HBV infection were analyzed to determine the relationships among these factors. Methods : Ninety children have been chosen from those who have visited to the Department of Pediatrics at St. Vincent's Hospital in The Catholic University of Korea from July 1st, 1995 to June 30th, 2000. The sample patients were followed up for over six months. HBV markers and liver function tests were all performed. Results : All children were asymptomatic at presentation. Eighty-three percent of the children had a history of chronic HBV infection in their families. Eighty-one percent were HBeAg positive, 16% were anti-HBe positive, while 3% were all HBeAg and anti-HBe negative. The prevalence of HBeAg among three age groups : 0~5; 6~10; and 11~15 year-old was 90%, 96% and 61% respectively. The prevalence of HBeAg in less than 10 year-old group was significantly higher than 11~15 year-old group(P=0.001). Serum ALT levels were within 40 IU/L in 64% children, 41~80 IU/L in 17%, 81~200 IU/L in 10%, and beyond 201 IU/L in 9%. The percentage of abnormality of ALT levels in HBeAg positive patients was significantly higher than that of HBeAg negative(P=0.036). Eleven of the 73 HBeAg positive children lost their HBeAg and seroconverted to anti-HBe. In these cases, all had transient elevations in ALT levels before HBeAg seroconversions. The annual rates of spontaneous seroconversion of HBeAg and HBsAg were 9.7% and 0.6%, respectively. Conclusion : Recognition of the dynamics of these changes in viral markers and biochemical findings is needed in the selection and evaluation of therapeutic regimens, establishment of treatment, and calling for controlled trials with adequate follow-up. The hepatitis B carrier state may be asymptomatic in children however, continued surveillance of carriers is important to determine the individual adverse prognostic factors of chronic HBV infections.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.6 no.2
• /
• pp.140-151
• /
• 2003

Purpose: We tried to evaluate the long term efficacy and positive predictive factors of interferon-alpha treatment in children with chronic hepatitis B. Methods: The study population included 113 children who received interferon therapy between May 1982 and July 2002 (20 years) for chronic hepatitis B in Department of Pediatrics, Yonsei University College of Medicine. Male to female ratio was 2.3 : 1 and the mean age at diagnosis was $11.1{\pm}4.1$ years old. Response to treatment was defined as normalization of alanine aminotransferase (ALT), disappearance of HBeAg and HBV-DNA Eighty two children responded while 32 did not. Interferon-alpha was given intramuscularly for 6 months at a dosage of $3{\times}10^6$ unit, 3 times weekly. In relapsed cases, lamivudine or interferon retreatment was done. Results: Seroconversion rate was 77.0% in terms of HBeAg, 74.3% in terms of HBV-DNA, and 80.5% in terms of ALT normalization after treatment. Seroconversion rate of both HBeAg and HBV-DNA was 72.6%. Analyzed by life table method, the effect of the treatment had been maintained over 10 years after cessation of therapy. Pre-treatment ALT level was the only significant positive predictive factor of response. Eleven cases (13.4%) relapsed, and 2 out of 3 showed response when treated with lamivudine and 1 out of 3 with interferon retreatment. Conclusion: Interferon-alpha showed significant efficacy in the treatment of chronic hepatitis B in our study. Further studies about the effect of interferon therapy on complications of hepatitis such as hepatocarcinoma, cirrhosis are warranted.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1993.11a
• /
• pp.39-40
• /
• 1993

Hepatitis B virus (HBV)is a member of the Hepadna virus family whose members share a characteristic virion structure and genome size, around 3.2kb in a paritially double-stranded form. The genome of HBV contains four overlapping open reading frames designated as P(polymerase). C(core), S(surface antigen)and X. The X gene has potential to encode 154 amino acids protein.

• Korean Journal of Clinical Laboratory Science
• /
• v.43 no.2
• /
• pp.57-67
• /
• 2011

In this study, we investigated the correlation between the administration of various antiviral agents and the alternation of specific biomarkers induced by the hepatitis B virus (HBV). Eligible subjects diagnosed with chronic hepatitis B were prescribed with antiviral drugs at the Gastroenterology Internal Medicine Department of E University Hospital in Daejeon between May 2004 and September 2009. Lamivudine was prescribed to 66 out of 100 patients. Of the 12 patients, 6 (50.0%) showed a change from being HBe-antigen-positive to being HBe-antigen-negative. Of the 39 patients, 23 (59.0%) showed higher than 40 IU/L alanine aminotransferase (ALT). Of the 65 patients, 41 (63.1%) showed HBV DNA decrease of 1 log, and were prescribed with Lamivudine. Adefovir was prescribed to 3 out of 100 patients. Of the 12 patients, 1 (8.3%) showed a change from being HBe-antigen-positive to being HBe-antigen-negative, and was prescribed with Adefovir. Entecavir was prescribed to 19 (19.0%) out of 100 patients. Of the 12 patients, 3 (25.0%) showed a change from being HBe-antigen-positive to being HBe-antigen-negative. Of the 12 patients, 3 (125.8%) showed higher than 40 IU/L ALT. Of the 65 patients, 14 (21.5%) showed HBV DNA decrease of 1 log, and were prescribed with Entecavir. Clavudine was prescribed to 7 out of 100 patients. Of the 12 patients, 1 (8.3%) showed a change from positive HBe antigen to negative HBe antigen. Of the 39 patients, 5 (12.8%) showed higher than 40 IU/L ALT. Of the 65 patients, 6 (9.2%) showed HBV decrease of 1 log, and were prescribed with Clavudine. These results do not show a statistically significant correlation between drugs and biomarkers. Data on combination therapy using Lamivudine and Adefovir show no statistically significant difference between drugs and biomarkers. Medications for periodic inspection was not correlated to HBe-antigen-negative conversion, ALT, and HBV DNA. HBV DNA was significantly reduced in patients with high levels of AST(aspartic acid aminotransferase) and ALT before treatment. In addition, the decrease of HBV DNA after 12 months of treatment was less frequently observed in patients treated with Lamivudine compared with other drugs. This result is associated with Lamivudine resistance. Although the association of drugs with diagnostic markers and the correct choice of treatment is difficult to determine, these results may be useful for further research on diagnosis and treatment of the hepatitis B virus.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.14
• /
• pp.6019-6026
• /
• 2015

Background: The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. Materials and Methods: We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. Results: No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. Conclusions: Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.

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

• Journal of Microbiology
• /
• v.37 no.2
• /
• pp.86-89
• /
• 1999

An OTHBVS cell line from HepG2 was established. This cell line stably expresses the human hepatitis B virus (HBV) middle S protein that includes the preS2 region which is important for HBV particle entry into the hepatocyte. To establish this cell line, the middle S open reading frame (ORF), with a promoter located in the 5' region and enhancer located in the 3' region, was cloned downstream from the metallothionine (MT) promoter of the OT1529 vector. In this vector, expression of the middle S protein was constructed to be regulated by its own promoter and enhancer. Expression of the large S protein which contains the preS1 region in addition to the middle S protein was designed to be regulated by the MT promoter. When extracts of OTHBVS cells were examined with an S protein detection kit (RPHA, Korea Green Cross Co.), an S protein was detected. Total mRNA of OTHBVS cell examined by northern blot analysis with an S ORF probe revealed small/middle S transcripts (2.1 kb). When the MT promoter was induced by Zn, large S transcripts (2.4 kb) were detected. The GP36 and GP33 middle S proteins were presumably detected, but large S proteins were not detected by immunostain analysis using anti-preS2 antibody.