• Molecules and Cells
• /
• v.45 no.3
• /
• pp.148-157
• /
• 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.

• Biomedical Science Letters
• /
• v.18 no.3
• /
• pp.283-290
• /
• 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
• /
• v.2 no.1
• /
• pp.211-220
• /
• 1985

Serum HBsAg, AntiHBs, HBeAg, AntiHBe and AntiHBc were detected by radioimmunoassay in 39 patients with acute viral hepatitis, 79 patients with chronic hepatitis, 30 patients with liver cirrhosis, 16 patients with primary hepatocellular carcinoma, 14 patients of HBsAg carriers and 129 cases of controls:78 cases of normal level of SGOT, SGPT, and 51 cases of elevated level of SGOT, SGPT. Following results were obtained: 1. HBsAg was detected in 66.7% of acute viral hepatitis, 63.3% of chronic hepatitis, 36.7% of liver cirrhosis, 81.3% of primary hepatocellular carcinoma and 27.1% of controls. 2. AntiHBs was positive in 0% of acute viral hepatitis, 21.5% of chronic hepatitis, 36.7% of liver cirrhosis, 31.3% of primary hepatocellular carcinoma, 0% of carrier and 44.2% of controls. 3. HBeAg was detected in 45.6% of chronic hepatitis, 23.3% of liver cirrhosis and 31.3% of primary hepatocellular carcinoma. 4. Among chronic liver diseases, antiHBe was positive in 56.3% of primary hepatocellular carcinoma, 23.3% of liver cirrhosis and 20.3% of chronic hepatitis. 5. AntiHBc was detected in most of all examines and the significance of presence of AntiHBc does not seem to represent liver disease itself but the evidence of infection of HBV. 6. Among 14 HBV carriers, 6 cases presented with abnormal SGOT, SGPT. 7. All HBV markers were negative in 5.1% of acute viral hepatitis, 5.1% of chronic hepatitis and 14.7% of controls: 17.6% of subjects with abnormal SGOT, SGPT and 12.8% of subjects with normal SGOT, SGPT. 8. Beside of HBV, other causes, such as non A, non B virus, Delta-agent, other viruses or related factors should be excluded among the patients with evidence of HBV infection associated with elevation of SGOT & SGPT.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.23 no.4
• /
• pp.311-318
• /
• 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.

• Research in Community and Public Health Nursing
• /
• v.13 no.3
• /
• pp.503-512
• /
• 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
• /
• v.3 no.1
• /
• pp.56-62
• /
• 2000

Purpose: The aim of this study was to evaluate the efficacy and histologic changes of interferon-alfa therapy on chronic hepatitis B virus infection in children. Patients and Methods: Thirty five children aged 3~16 years who were seropositive for HBV DNA, HBsAg and HBeAg were enrolled. Interferon-alfa 2a ($3.4\;MU/m^2$) were given for 6 months. Serologic markers of viral replication was evaluated 1 year after therapy. Post treatment liver biopsy was performed in 18 patients who showed serologic response. Results: Serum HBeAg and viral DNA became negative in 22 (63%) of treated children at 12 months after therapy. Serum aminotransferase levels normalized in all of the responders and HBsAg became negative in one responder. Horizontal transmission, serum aminotransferase levels more than twice normal, and active inflammation on liver biopsy were predictive factors for response to interferon therapy. Periportal piecemeal necrosis, lobular activity, portal inflammation, fibrosis, and total histologic activity index were reduced in responders. Conclusion: In children with chronic hepatitis B, interferon alfa promotes loss of viral replication and improves aminotransferase. Serologic response is associated with improvement in hepatic histology.

• Bulletin of the Korean Chemical Society
• /
• v.26 no.9
• /
• pp.1385-1389
• /
• 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
• /
• v.15 no.2
• /
• pp.637-642
• /
• 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
• /
• v.17 no.7
• /
• pp.3381-3384
• /
• 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.

• The Korean Journal of Nuclear Medicine
• /
• v.17 no.2
• /
• pp.49-55
• /
• 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.