• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.178-178
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• 1996

Hepatitis B virus (HBV) infection is one of the serious problems in Southeast Asia including Korea because it causes chronic hepatitis, which can easily be transformed In fatal conditions such as cirrhosis and hepatoma. Even though lots of informations on structural characteristics and gene expression mechanisms have been accumulated, the mechanism for HBV-induced hepatocellular injury which is believed to be the consequences of the immunological response is not well understood. In order tn perform immunopathological studies for prevention and treatment of HBV infection, we designed transgenic mice as a disease model which can mimic HBV infection, In this study, a promoter-HBV DNA fragment for the preparation of HBV transgenic mice has been constructed. To add a proper enzyme site on 5' end of HBV gene, total HBV (subtype adr) gene was inserted into BamHI site of pBluescript SK vector and reextracted by PstI-SacI treatment A liver-specific promoter, rat ${\alpha}$ 2u globulin gene promoter, was insrted to pBluescript SK vector and reextracted by BamHI-PstI treatment, Promoter-HBV DNA was constructed by ligation of two fragments using identical PstI sites. For large scale production of promoter-HBV DNA, it was inserted to BamHI-SacI site of pBluescript SK vector.

• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2395-2399
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• 2016

Background: Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Cytokines play an important role in the regulation of immune responses and defense against viral infections. Human interleukin 6 (IL6) is a multifunctional cytokine that participates in these processes. Objective: The aim of this study was to assess the IL6-174 gene polymorphism in patients with chronic hepatitis B virus (HBV) infection as compared with healthy controls in an Iranian population. Materials and Methods: Totals of 297 HBV patients and 368 control individuals were evaluated. Genomic DNA was extracted from peripheral blood and the SSP-PCR (sequence specific primer-polymerase chain reaction) method was applied for genotyping. Results: The frequencies of genotypes C/C, G/G and C/G in HBV cases were 4.7%, 34.3%, 60.9% and in controls were 12.8%, 39.7% and 47.6%, respectively. The frequencies of G and C allele in patients and controls were 78.1%, 21.9% and 67.4%, 32.6 % respectively. There was a significant difference in the frequencies of G/G genotype (CI=1.8-7.1, OR=3.47, P=0.00001) and G allele (CI=1.34-2.23, OR=1.72, P=0.0001) between HBV patients and the control group. Conclusions: These findings suggest that the IL6-174 C/G genotype and the G allele are strongly associated with susceptibility to HBV infection. Demographic information showed that most of the subjects were male (74.4%). According to high frequency of G/G genotype in male participants (63.1%) men probably are more susceptible to hepatitis than women.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2002년도 추계학술대회초록집
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• pp.145-145
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• 2002

Chronic viral infection has been reported to cause a range of hepatic lesion, including hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC) in a wide variety of animal species. Woodchucks (Marmota monax) chronically infected with woodchuck hepatitis virus (WHV) develop similar progressive hepatic inflammatory and neoplastic lesions that are remarkably similar to those associated with HBV infection in humans. Twenty two-month-old offspring from woodchucks (Marmota monax) experimentally infected with woodchuck hepatitis virus, were purchased. One randomly chosen animal was autopsied. The liver exhibits marked cirrhotic changes characteristic of the pre-transformation phase of WHV. We believe that this may represent a new suitable and cost-effective model for the disease processes associated with hepadnaviruses in a number of other species, most notably Hepatitis B virus infection in man.

• Journal of Preventive Medicine and Public Health
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• 제33권3호
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• pp.323-333
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• 2000

Objectives : Chronic HBsAg carriers are the principal source of infection for other susceptible people, and are themselves at high risk of developing serious liver diseases. In Korea, it has been estimated that 65-75% of the HBsAg positives remained as persistent carriers. Additionally, familial clustering of MBV infection has frequently been observed among carriers. Some would become progressive, chronic hepatitis patients, and others would not. The aim of this study was to evaluate the association between various factors, such as the duration of infection, type of virus, mutation of precore/core region in HBV, major histocompatibility class-I, and developing chronic liver diseases among familial HBV carriers. Methods : Chronic carrier status was identified by repeated serological tests for HBsAg at intervals of six months or more. A familial chronic carrier was defined when the disease was observed in a family member over two generations. Two families were recruited, among which a total of 20 chronic HBsAg carriers(11 carriers in No.1, and 9 in No.2 family) were identified. Data on the general characteristics and liver disease status were collected. Identification of the HBV-DNA was successful only for 13 subjects among the 20 carriers. Analysis of viral DNA in terms of subtype, pre-core and core region mutations was carried out. The type of major histocompatibility class-1 for the 13 subjects was also analysed. Results & Conclusions : Seven of 10 chronic HBV carriers of the 1st generation and one of 10 of the 2nd generation were clinical patients with chronic hepatitis, the others, three of the 1 st and nine of the 2nd generation, were asymptomatic carriers. This data indicates that the duration of HBV carriage is one of the major factors for disease severity. The subtype of HBsAg analysed using MBV-DNA identified in 13 carriers were adr, and the pattern of precore nonsense mutation in HBV-DNA was identical among family members, which meads that the same virus strains were transmitted between the family members. The association between the precore or core mutations in HBV-DNA and the disease severity was not observed. While it was suggested that a specific type of MHC class-I may be related to disease progression.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권2호
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• pp.137-142
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• 2008

목 적: 인터페론은 소아 만성 B형 간염의 치료에 널리 쓰이고 있으나 50% 이상의 환자에서 인터페론 치료에 반응이 없어 추가적인 다른 치료가 필요하다. 라미부딘은 B형 간염 바이러스 복제의 억제제로 B형 간염 치료제로 널리 쓰이고 있으나, 인터페론 치료에 반응이 없었던 B형 간염 환자에 대한 라미부딘의 치료 효과에 대한 연구가 많지 않다. 방 법: 2000년 1월부터 2007년 12월까지 부산대학교병원 소아청소년과에서 만성 B형 간염으로 진단되어 인터페론(interferon ${\alpha}$-2b, 10 $MU/m^2$ 또는 pegylated interferon $1.5{\mu}g/kg$)으로 6개월 간 치료를 받은 33명 중 치료에 반응이 없어 치료 종결 후 6~12개월 뒤부터 라미부딘(3 mg/kg/일, 최고 100 mg/일)으로 치료를 한 8명(남 6명, 여 2명)을 대상으로 라미부딘의 치료 효과를 분석하였다. 임상적 소견에 대해 의무기록지를 후향적으로 검토하였다. 결 과: 인터페론 치료 시작 시 나이는 4.9${\pm}$3.1세, 라미부딘 치료 시작 시 나이는 6.1${\pm}$3.2세였다. 인터페론 치료 전 혈청 ALT는 148.1${\pm}$105.8 IU/L였고, HBV-DNA PCR log값은 6.95${\pm}$0.70 copies/mL였다. 인터페론 치료 후 ALT는 143.1${\pm}$90.4 IU/L였고, DNA PCR log값은 6.46${\pm}$2.08 copies/mL로 치료 전과 차이가 없었고(p> 0.05), 2명에서 HBeAg 음전이 있었다. 모든 환자에서 라미부딘 치료 후 7.4${\pm}$2.1개월에 ALT가 정상화되고, 이미 HBeAg이 음전된 2명을 제외한 6명에서 7.9${\pm}$2.1개월에 HBeAg 혈청전환이 있었다. HBV DNA는 2.4${\pm}$2.8개월에 7명(87.5%)에서 음성화되었다. 2명은 라미부딘치료 종결 후 3년 이상 재발이 없으며, 5명은 완전 반응상태로 24.4${\pm}$9.1개월간 복용 중이다. 1명은 12개월간 라미부딘을 복용하여 혈청 ALT가 정상화되고 HBeAg 혈청전환이 있었으나 바이러스 돌파현상이 발생하여 치료를 중단하였다. 결 론: 연구 대상 환자 수가 적었지만 인터페론 치료에 반응이 없었던 만성 B형 간염 환자에서 라미부딘의 치료는 매우 효과적이었다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제11권2호
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• pp.130-136
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• 2008

목 적: 소아 만성 B형 간염 환아들에서 라미부딘 치료의 효과와 지속성에 대해 알아보고자 하였다. 방 법: 1998년 1월부터 2008년 5월까지 서울아산병원 소아과에서 만성 B형 간염으로 진단받고 라미부딘치료를 받은 44명의 환아들의 의무기록을 후향적으로 분석하였다. 12개월 이상 추적 관찰했던 환아들을 대상으로 발병시 성별, 연령, 치료 전후의 ALT, 혈청 HBVDNA, HBeAg, anti HBe, HBsAg, anti HBs의 변화를 조사하였고, 치료의 지속성과 내성 발현에 대해 조사하였다. 결 과: 라미부딘 치료 후 3년 이내에 총 44명의 환아중 21명(48%)에서 혈청 전환이 이루어졌고, 34명(77%)에서 HBV DNA가 음전되었으며, 41명(93%)에서 혈청ALT가 정상화되었다. Kaplan-Meier법에 의한 HBeAg 누적 혈청 전환율은 3년째에 60%로 나타났다. 치료를 마친 환아 25명 중 혈청 전환된 18명의 환아 모두 약물중단 이후 최대 3년 추적 관찰시 재발 없이 지내고 있어 라미부딘 치료 반응의 지속성을 보여 주었다. 치료 중 12명(27%)에서 돌파 현상이 나타났고, 11명(25%)에서 YMDD 돌연변이가 발견되었다. 치료 전 혈청 ALT 수치는 혈청 전환을 이룬 군에서 더 높았지만, 통계적 유의성은 없었다(338${\pm}$542 IU/L vs. 144338${\pm}$163 IU/L, p> 0.05). 결 론: 만성 B형 간염 환아에서 라미부딘 치료시 절반 정도에서 치료 효과를 기대할 수 있었다. 라미부딘의 치료 반응은 장기적으로 지속되었으며, 향후 약제 내성 돌연변이의 증가에 따른 이차 약제에 대한 추가적인 연구가 필요하다고 생각된다.

• IMMUNE NETWORK
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• 제10권4호
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• pp.126-134
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• 2010

Background: $CD8^+$ T cells contribute to the clearance of Hepatitis B virus (HBV) infection and an insufficient $CD8^+$ T cell response may be one of the major factors leading to chronic HBV infection. Since the HBx antigen of HBV can up-regulate cellular expression of several immunomodulatory molecules, we hypothesized that HBx expression in hepatocytes might affect $CD8^+$ T cell activity. Methods: We analyzed the activation and apoptosis of $CD8^+$ T cells co-cultured with primary hepatocytes rendered capable of expressing HBx by recombinant baculovirus infection. Results: Expression of HBx in hepatocytes induced low production of $interferon-{\gamma}$ and apoptosis of CD8+ T cells, with no effect on CD8 T cell proliferation. However, transcriptional levels of H-2K, ICAM-1 and PD-1 ligand did not correlate with HBx expression in hepatocytes. Conclusion: Our results suggest that HBx may inhibit $CD8^+$ T cell response by regulation of $interferon-{\gamma}$ production and apoptosis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3555-3559
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• 2013

Chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1) are major risk factors for hepatocellular carcinoma (HCC). The aim of this study was to evaluate the role of HBV genetic variation and the R249S mutation of the p53 gene, a marker of AFB1-induced HCC, in Thai patients chronically infected with HBV. Sixty-five patients with and 89 patients without HCC were included. Viral mutations and R249S mutation were characterized by direct sequencing and restriction fragment length polymorphism (RFLP) in serum samples, respectively. The prevalences of T1753C/A/G and A1762T/G1764A mutations in the basal core promotor (BCP) region were significantly higher in the HCC group compared to the non-HCC group. R249S mutation was detected in 6.2% and 3.4% of the HCC and non-HCC groups, respectively, which was not significantly different. By multiple logistic regression analysis, the presence of A1762T/G1764A mutations was independently associated with the risk of HCC in Thai patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.35-39
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• 2015

Background: Hepatocellular carcinoma (HCC) is one of the most frequent cancers in South East Asian countries including Cambodia, where prevalence of chronic carriers of hepatitis B and C virus (HBV and HCV) is reported to be very high. We reviewed HCC cases admitted to a cancer hospital in Phnom Penh, which is the only one hospital for cancer treatment and care in Cambodia during the study period. Materials and Methods: Information was collected from medical records of 281 cases (210 males and 71 females) diagnosed as primary HCC from 2006 to 2011. Results: The subjects were 7-81 years old with a median age of 53 years. Hypochondriac pain was the most common complained symptom (74%). One third of the cases presented with jaundice. Nearly half had ascites at their first visit. One third had liver cirrhosis. Nearly three fourths of the cases presented with tumor sized more than 50 mm in diameter, and in almost all cases (97.4%) the size was more than 20 mm. Among 209 subjects tested, hepatitis virus carriers were 75.6%; 46.4% for HBV only, 21.5% for HCV only, and 7.7% for both viral infections. Median age of patients with HBV was about ten years younger than those with HCV. Conclusions: This study revealed the characteristics of HCC cases in Cambodia, although there were several limitations. Most HCC cases were infected with HBV and/or HCV, and diagnosed at late stages with complications. This implicated that public health intervention to prevent HBV and HCV infection is of high priority.

• Journal of Ginseng Research
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• 제7권2호
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• pp.115-124
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• 1983

The effect of ginseng administration on the patients of acute viral (B type) hepatitis has been oberved and the results were as follows. The albumin/globulin ratio of the ginseng administered group has significantly improved 4 weeks after admission while that of control group has not been improved suggesting that the ginseng might be effective in improving the protein metabolism. The thymol turbidity test again gave a similar result. Recovery of the disorder of bilirubin metabolism was also accelerated in the ginseng administered group compared with control group. The raised bilirubin value of the former returnedto the normal value 2 week after admission while that of the latter reached to normal 4-5 weeks after admission. However no significant difference of the bilirubin level between ginseng treated and non-treated groups could be observed. Cholesterol metabolism is also stimulated in ginseng administered group. The lowered cholesterol level of the ginseng group returned to normal 3-4 weeks after admission while that of latter reached to normal 5-6 weeks after admission. The raised S-GOT and S-GPT levels of the ginseng treated group returned to the normal value 3-4 weeks after admission while those of control group rehimed to normal in 5 weeks after admission suggesting that the ginseng improved impaired liver function. The improvement of the raised transaminase level seemed to be accelerate6 by the ginseng administration, however, no significant difference of the transaminase level between the ginseng treated and non-treated group could be observed. A significant effect of ginseng on the raised alkaline phosphatase level was observed. From the above results, it seemed that ginseng might stimulate the improvement of the disturbance of liver function, particularly at the early phase of its development of acute liver disease suggesting that panax ginseng might play a significant role in preventing the disease developing to be chronic.