• Molecules and Cells
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• 제45권3호
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• pp.148-157
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• 2022

Hepatitis C virus (HCV) is a major cause of chronic liver disease and is highly dependent on cellular proteins for viral propagation. Using protein microarray analysis, we identified 90 cellular proteins as HCV nonstructural 5A (NS5A) interacting partners, and selected telomere length regulation protein (TEN1) for further study. TEN1 forms a heterotrimeric complex with CTC and STN1, which is essential for telomere protection and maintenance. Telomere length decreases in patients with active HCV, chronic liver disease, and hepatocellular carcinoma. However, the molecular mechanism of telomere length shortening in HCV-associated disease is largely unknown. In the present study, protein interactions between NS5A and TEN1 were confirmed by immunoprecipitation assays. Silencing of TEN1 reduced both viral RNA and protein expression levels of HCV, while ectopic expression of the siRNA-resistant TEN1 recovered the viral protein level, suggesting that TEN1 was specifically required for HCV propagation. Importantly, we found that TEN1 is re-localized from the nucleus to the cytoplasm in HCV-infected cells. These data suggest that HCV exploits TEN1 to promote viral propagation and that telomere protection is compromised in HCV-infected cells. Overall, our findings provide mechanistic insight into the telomere shortening in HCV-infected cells.

• 대한의생명과학회지
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• 제18권3호
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• pp.283-290
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• 2012

In this study, we investigated the virological characteristics, HBV DNA levels and presence of mutations of "a" determinant in the HBsAg S gene in chronic hepatitis B patients with coexisting HBsAg and anti-HBs. The 18 patients who were diagnosed with chronic hepatitis B were both positive for HBsAg and anti-HBs. HBV Among them, 15 patients were DNA positive. The median of HBV DNA levels in serum was $2.18{\times}10^7$ copies/mL with the HBsAg+/anti-HBsAb+ patients. Also, 4 of 8 HBeAg negative patients had HBV DNA levels higher than $10^4$ copies/mL and the median of HBV DNA levels was $2.03{\times}10^6$ copies/mL, which were significantly high. These results showed that viral replication still existed in most of the patients of the concomitant HBsAg and anti-HBs, and even in the some HBeAg negative patients. Furthermore, mutation within the "a" determinant of HBV were found in 7 of 15 patients. The most frequent changes were located at positions aa126. In addition, one mutation observed for HBsAg only positive.

• Journal of Yeungnam Medical Science
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• 제2권1호
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• pp.211-220
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• 1985

저자들은 급성간염 39예, 만성간염 79예, 간경변증 30예, 원발성간암 16예, 보유자 14예 및 비교군 129예의 모두 307명을 대상으로 하여 SGOT, SGPT 및 HBV 표식자를 조사하여 다음의 결과를 얻었다. 1. HBsAg의 발현율은 급성간염의 66.7%, 만성간염의 63.3%, 간경변증의 36.7%, 원발성간암의 81.3% 및 비교군에서 27.1%인 것으로 나타났다. 2. AntiHBc의 발현율은 급성간염의 0%, 만성간염의 21.5%, 간경변증의 36.7%, 원발성간암의 31.3%, 보유자의 0% 및 비교군에서 44.2%로 나타났다. 3. HBeAg은 만성간질환중 만성간염에서 45.6%로 가장 높게 나타났고 AntiHBe는 원발성간암에서 56.3%로 가장 높았다. 4. AntiHBc는 각종 간질환, 보유자 및 비교군에서 높게 나타났으며 이는 AntiHBc자체는 간질환에 직접 관계가 없는 감염의 흔적으로 생각된다. 5. HBsAg 보유자 14명중 6명(42.3%)에서 혈청 GOT, SPT 치의 이상 상승이 있었다. 6. HBV에 감염된 혈청학적 증거가 있으면서 간기능에 이상이 있을 때, HBV 이외에 non-A, non-B 바이러스, Delta agent 또는 타 바이러스나 관련된 다른 요인과의 관계가 있을 수 있는 점을 고려하여야 할 것으로 생각된다. HBV의 5 가지 표식 자가 모두 음성으로 나타난 환자는 급성간염의 5.1%, 만성간염의 5.1%에 달했으며, 이것은 HBV 이외의 다른 원인이 병인이 될 수 있음을 시사하며 비교군 중 SGOT, SGPT치의 증가를 보인 군에서는 17.6%, 정상 SGOT, SGPT치를 나타낸 군에서는 12.8%에서 모든 HBV 표식자가 음성으로 나타났다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권4호
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• pp.311-318
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• 2020

Chronic hepatitis B viral (HBV) infection remains a major health threat, especially in high-prevalence areas. Most infants infected by mother-to-infant HBV transmission become chronic carriers. In Taiwan, many important preventive interventions have been implemented to block the perinatal transmission of HBV in the past 35 years. The first nationwide universal HBV vaccination program was launched in Taiwan in July 1984. The three-dose HBV vaccine completion rate reached 98.1% in 2018. The prevalence of Hepatitis B surface antigen (HBsAg) decreased from 9.8% in pre-vaccinated period in 1984 to 0.5% in the vaccinated cohort in 2014. The incidence of hepatocellular carcinoma in children aged 6-9 years significantly declined from 0.52 to 0.13 per 100,000 children born before and after 1984, respectively. Furthermore, we have performed a maternal HBV screening program during pregnancy since 1984, with the screening rate peaked at 93% in 2012. The HBsAg- and HBeAg-seropositive rate in pregnant women declined from 13.4% and 6.4% in 1984-1985 to 5.9% and 1.0% in 2016, respectively. To closely control perinatal HBV infection, we have administered hepatitis B immunoglobulin immediately after birth and checked the serum level of HBsAg and anti-HBs in high-risk babies born to HBsAg-seropositive mothers, irrespective of their HBeAg status, since July 2019. We have also adopted short-term antiviral treatments such as tenofovir 300 mg daily in the third trimester for highly viremic mothers and reduced the perinatal infection rates from 10.7 to 1.5%. Through all these efforts, we expect to meet the global goal of eliminating HBV infection by 2030.

• 지역사회간호학회지
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• 제13권3호
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• pp.503-512
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• 2002

Purpose: This study was conducted to develop educational materials for preventing type B viral hepatitis infection. Prior to this study, a survey had been conducted to define the educational needs of persons with hepatitis B antigen. Method: Based on the results of the former study and a review of the literature, the content of the educational materials was confined to the transmission cycle and its prevention in type B hepatitis. A professional team that consisted of writers and producers videotaped the lectures provided by professors and instructors in a nursing school. A professional graphic designer produced the leaflet to enhance the visual effects. Results: The contents of the educational materials for type B hepatitis were composed of six parts: (1) the prevalence rate (or morbidity) of type B hepatitis antigen positive and its recent trend, (2) transformation of hepatitis. (3) transmission cycle of hepatitis infection, (4) persons who are susceptible to hepatitis and need a vaccination, (5) preventive approach hepatitis vaccination and the guideline for patients' daily lives for preventing infection and (6) questions and answers. The materials were delivered in the form of lectures, visual charts, graphics, and multi-media. Conclusion: The educational materials developed in this study may provide practical information and knowledge on strategies to prevent type B hepatitis. The educational materials may be utilized in primary health care centers or school health services.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제3권1호
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• pp.56-62
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• 2000

목 적: 만성 B형 간염 환자의 치료에 interferon alfa는 효과가 있는 것으로 알려지고 있지만 연구자에 따라 차이가 있으며 소아에서의 치료 후의 조직학적 변화에 대한 연구는 거의 없는 실정이다. 저자들은 소아 만성 B형 간염에서 interferon alfa의 치료 효과와 추적 생검이 가능했던 환자에서의 조직학적 변화에 대해 알아보고자 하였다. 대상 및 방법: 1995년 3월부터 1997년 8월까지 서울대학교병원 소아과에서 6개월 이상 HBsAg과 HBeAg 및 HBV DNA가 양성이었으며 간 조직검사상 만성 간염으로 확진된 환자 35명을 대상으로 recombinant interferon alfa 3~6 MU(평균 $3.4\;MU/m^2$)를 주 3회씩 6개월간 피하주사 하였다. 치료 시작 12개월 이상 혈청학적 변화를 추적 관찰하였다. interferon에 반응이 있는 환자 중 18명에서 치료후 간생검을 실시하여 조직학적 변화를 분석하였다. 결 과: 1) 치료 환자 35명 중 17명(49%)에서 인터페론 치료 시작 6개월에 HBV DNA의 감소가 있었고, 12개월째에 22명(63%)에서 HBeAg 및 HBV DNA의 음전이 생겼으며 18개월까지는 25명(71%)에서 관찰되었다. 반응군에서 혈청 ALT치는 모두 정상화되었고, HBsAg의 음전은 1명에서 관찰되었다. 2) 어머니가 HBsAg 보유자가 아닌 수평감염, 치료전 ALT가 정상의 2배 이상, 간조직의 심한 괴사와 염증이 interferon에 대한 반응이 좋은 예측인자이었다. 3) 치료 후 반응군의 간조직 소견에서 간맥주위괴사, 소엽내 활성도, 간맥내 염증, 간섬유화, total HAI가 유의하게 감소하였다. 결 론: 소아 만성 B형 간염에서 interferon alfa 치료 후 63%에서 반응을 보였으며, 혈청학적 변화는 조직학적 소견의 호전과 연관이 있다. 소아 만성B형 간염 환아에서 interferon 치료는 혈청학적, 생화학적, 조직학적 관해를 유도하는 효과적이고 안전한 치료방법이다.

• Bulletin of the Korean Chemical Society
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• 제26권9호
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• pp.1385-1389
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• 2005

Human hepatitis B virus (HBV) is a pathogen related to the development of liver diseases including chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). However, the efficient methods to suppress HBV replication have not been developed yet. Therefore, we have used RNA interference (RNAi) as a potential tool for the suppression of HBV replication. Here, we designed a 21 nt small intefering dsRNA (siRNA) against hepatitis B virus X (HBx) RNA with 3' overhanging ends derived from T7 promoter. It has been reported that HBV X protein plays an important role in HBV gene expression and viral replication. The suppression of HBx gene expression by the 21 nt siRNA was investigated by Northern blot analysis and chloramphenicol acetyl transferase (CAT) assay. The level of HBx mRNA was decreased by siRNA in a dose-dependent manner. We also found that the 21 nt siRNA inhibited the HBV replication in hepatocellular carcinoma cell.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.637-642
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• 2014

The pathogenesis of hepatocellular carcinoma (HCC) related to habitual betel quid (BQ) chewing is unclear. Risk of HCCis increased with adverse hepatic fibrosis. This study aimed to assess the impact of chronic viral hepatitis on adverse hepatic fibrosis in HCC related to BQ chewing. This hospital-based case-control study enrolled 200 pairs of age- and gender-matched patients with HCC and unrelated healthy controls. Serologic hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), ${\alpha}$-fetoprotein (AFP), and surrogate markers for significant hepatic fibrosis were measured. Information on substance-use habits was obtained with a questionnaire. By analysis of surrogate markers for hepatic fibrosis, the prevalence of significant hepatic fibrosis in patients chewing BQ was between 45.8% and 91.7%, whereas that for patients without BQ chewing was between 18.4% and 57.9%. The difference was significant (P <0.05 for each surrogate marker). Multivariate analysis indicated that cirrhosis with Child-Pugh C (odds ratio (OR) = 3.28; 95% confidence interval (CI), 1.29-8.37), thrombocytopenia (OR = 3.92, 95% CI, 1.77-8.68), AFP >400 mg/L (OR = 2.21, 95% CI, 1.05-4.66) and male gender (OR = 4.06, 95% CI, 1.29-12.77) were independent factors associated with habitual BQ chewing. In conclusion, adverse hepatic fibrosis and severe liver damage play important roles in the pathogenesis of BQ-related HCC, which could be aggravated by chronic hepatitis B and hepatitis C. BQ-cessation programs and prevention of chronic HBV/HCV infection are needed to prevent HCC related to BQ chewing.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3381-3384
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• 2016

Background: Hepatitis B virus (HBV) is a key factor for hepatocellular carcinoma (HCC). About 350 million people are affected by chronic infection which is related to the rapid development of liver diseases as well as hepatitis, cirrhosis and hepatocellular carcinoma. Expression of tumor necrosis factor alpha (TNF-${\alpha}$) in the liver demonstrates a major genetic polymorphism which is involved in resistance or susceptibility to chronic HBV infection. Materials and Methods: In this study, two populations were studied by the sequence specific primer-polymerase chain reaction (SSP-PCR) method: HBV cases (n=409), who were HBS-Ag+, and healthy controls (n=483). Results: The results shown that the frequency of TNF-${\alpha}$ -308 G/G genotype in healthy controls (47.2%) was significantly higher than in HBV infected patients (28%) (CI = 1.29-2.61, OR = 1.83, P = 0.0004). Also TNF-${\alpha}$ -308 A/A and A/G genotype frequencies in the healthy controls were 4.6% and 48.2% and in patient group were 19.5% and 52.5% (CI = 2.23-7.12, p: 0.0001, OR: 3.94) respectively. Conclusions: We found that among Iranian people TNF-${\alpha}$ -308A allele not only has the highest genotype frequency but also it has the highest frequency in the world population. In addition, TNF-${\alpha}$-308 G/G polymorphism was associated with HBV resistance, whereas TNF-${\alpha}$-308A (A/A or A/G) polymorphism appeared to associated with chronic HBV infection. These data suggested that among the Iranian population, the -308 G/G polymorphism of TNF-${\alpha}$ gene promoter region has the potential to influence the susceptibility to HBV infection and it may be responsible for viral antigen clearance.

• 대한핵의학회지
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• 제17권2호
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• pp.49-55
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• 1983

By radioimmunoassay, serologic markers of Hepatitis B Virus were studied in 44 patients with acute viral hepatitis, 10 patients with chronic persistent hepatitis, 10 patients with chronic active hepatitis, 44 patients with liver cirrhosis and 25 patients with primary hepato cellular carcinoma. The results were follows: 1) HBsAg was present in 77.2% of AVH, 40% of CPH, 80% of CAH, 55.1% of LC and 68 % of PHC. In this HBsAg positive groups, all but one in liver cirrhosis had Anti-HBc. 2) Anti-HBs was most commonly detected in CPR and accompanied by Anti-HBc except one case in AVH. 3) Anti-HBc was the only marker detected in 11.4% of AVH, 20% of CPH, 20% of CAH, 16.3% of LC and 8% of PHC. 4) HBeAg was most commonly found in HBsAg-positive CPH but Anti-HBe was most frequently detected in PHC. 5) The absence of HBV markers was noted in 2.3% of AVH, 10% of CPH, 8% of PHC except CAH and LC.