• Title/Summary/Keyword: Chronic Hepatitis B

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Tumor Necrosis Factor Alpha -308 G/A Single Nucleotide Polymorphism and Susceptibility to Hepatocellular Carcinoma Via Hepatitis B Infection

  • Azar, Saleh Shahbazi;Mansoori, Maryam;Attar, Marzieh;Shahbazi, Majid
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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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.

Hepatitis C Virus Nonstructural Protein 5A Interacts with Immunomodulatory Kinase IKKε to Negatively Regulate Innate Antiviral Immunity

  • Kang, Sang-Min;Park, Ji-Young;Han, Hee-Jeong;Song, Byeong-Min;Tark, Dongseob;Choi, Byeong-Sun;Hwang, Soon B.
    • Molecules and Cells
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    • v.45 no.10
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    • pp.702-717
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    • 2022
  • Hepatitis C virus (HCV) infection can lead to chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV employs diverse strategies to evade host antiviral innate immune responses to mediate a persistent infection. In the present study, we show that nonstructural protein 5A (NS5A) interacts with an NF-κB inhibitor immunomodulatory kinase, IKKε, and subsequently downregulates beta interferon (IFN-β) promoter activity. We further demonstrate that NS5A inhibits DDX3-mediated IKKε and interferon regulatory factor 3 (IRF3) phosphorylation. We also note that hyperphosphorylation of NS5A mediates protein interplay between NS5A and IKKε, thereby contributing to NS5A mediated modulation of IFN-β signaling. Lastly, NS5A inhibits IKKε-dependent p65 phosphorylation and NF-κB activation. Based on these findings, we propose NS5A as a novel regulator of IFN signaling events, specifically by inhibiting IKKε downstream signaling cascades through its interaction with IKKε. Taken together, these data suggest an additional mechanistic means by which HCV modulates host antiviral innate immune responses to promote persistent viral infection.

Inhibition of Hepatitis B Virus Replication by in vitro Synthesized RNA

  • Yang, Yeon-Ju;Heo, Young-Shin;Kim, Jeong-Ki;Kim, Sang-Yong;Ahn, Jeong-Keun
    • Bulletin of the Korean Chemical Society
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    • v.26 no.9
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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.

Comparison of Therapeutic Efficacy between Lamivudine and Alpha-Interferon in Korean Children with Chronic Hepatitis B at Two Years after the Initiation of Treatment (소아 만성 B형 간염 환아에서 라미부딘과 알파 인터페론의 치료효과 비교 : 치료 시작 후 2년 경과 시점 비교)

  • Choe, Byung-Ho;Jang, You Cheol;Jang, Chang Hwan;Oh, Ki Won;Lee, Jun Hwa;Ko, Cheol Woo
    • 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.

Nurses' Knowledge, Attitudes and Nursing Intention toward AIDS and Chronic Hepatitis B (간호사의 에이즈와 만성 B형 간염에 대한 지식과 태도 및 간호의도)

  • Han, Jong Sook;Cho, Hee;Kim, Youngmee;Kim, Ok Hyun
    • Korean Journal of Occupational Health Nursing
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    • v.21 no.3
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    • pp.201-208
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    • 2012
  • Purpose: This study aims at comparing nurses' knowledge, attitudes and nursing intention toward AIDS and Chronic Hepatitis B(CHB). Methods: The data were collected through self-reported questionnaires from 245 nurses between July and August, 2011. The nurses were recruited from 3 hospitals located in Seoul and Gyeonggi province. Pearson correlation coefficient and stepwise multiple regression were adopted to analyze the data. Results: Regarding AIDS, higher knowledge level was correlated with positive attitudes only(r=-.22, p<.001), which were correlated with favorable nursing intention(r=-.41, p<.001). Higher CHB knowledge level was correlated with both positive attitudes toward CHB(r=-.14, p= .030) and favorable nursing intention(r=.18, p= .004). Nursing intention toward AIDS was affected by attitudes(${\beta}$=.58, p<.001) and explained 16.6% of the variance. Both knowledge(${\beta}$=.35, p=.028) and attitudes(${\beta}$=-.49, p<.001) influenced nursing intention toward CHB and explained 19.1% of the variance. Conclusion: We need to promote nurses' positive attitudes toward AIDS to increase their nursing intention for people living with AIDS.

IFN-γ: A Crucial Player in the Fight Against HBV Infection?

  • Marine Laure Bettina Hillaire;Philip Lawrence;Brice Lagrange
    • IMMUNE NETWORK
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    • v.23 no.4
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    • pp.30.1-30.18
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    • 2023
  • About 0.8 million people die because of hepatitis B virus (HBV) infection each year. In around 5% of infected adults, the immune system is ineffective in countering HBV infection, leading to chronic hepatitis B (CHB). CHB is associated with hepatocellular carcinoma, which can lead to patient death. Unfortunately, although current treatments against CHB allow control of HBV infection, they are unable to achieve complete eradication of the virus. Cytokines of the IFN family represent part of the innate immune system and are key players in virus elimination. IFN secretion induces the expression of interferon stimulated genes, producing proteins that have antiviral properties and that are essential to cell-autonomous immunity. IFN-α is commonly used as a therapeutic approach for CHB. In addition, IFN-γ has been identified as the main IFN family member responsible for HBV eradication during acute infection. In this review, we summarize the key evidence gained from cellular or animal models of HBV replication or infection concerning the potential anti-HBV roles of IFN-γ with a particular focus on some IFN-γ-inducible genes.

Lack of Association between Tumor Necrosis Factor-α -308 and -238 Promoter Polymorphisms and Chronic Hepatitis B Virus Infection (종양괴사인자-α -308과 -238 promoter 다형성과 만성 B형 간염 바이러스 감염 간의 연관성 결여)

  • Jang, Won-Hee;Yang, Young-Il;Lee, Youn-Jae;Chun, Jin-Ho;Yea, Sung-Su;Seog, Dae-Hyun;Kim, Hyeong-In
    • Journal of Life Science
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    • v.18 no.9
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    • pp.1207-1211
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    • 2008
  • The pro-inflammatory cytokine tumor necrosis factor-$\alpha$ (TNF-$\alpha$) is an important mediator of the immune response in hepatitis B virus (HBV) infection. Since the production of TNF-$\alpha$ is mostly regulated at the transcriptional level and polymorphisms in the TNF-$\alpha$ promoter alter its expression, TNF-$\alpha$ promoter polymorphisms could affect the pathogenesis of chronic HBV infection. In this study, we investigated the potential association of TNF-$\alpha$ promoter polymorphisms with chronic HBV infection. The study included 181 patients with chronic HBV infection, 201 persons who had been spontaneously recovered from hepatitis B, and 170 unrelated healthy controls. The -308G/A and -238G/A polymorphisms in the TNF-$\alpha$ promoter were analyzed by PCR-restriction fragment length polymorphism. The distribution of both the -308 and -238 genotypes in the patient group was not statistically different from that in the spontaneous recovery and control groups (p>0.05). There was also no significant difference in the allele frequency between the groups (p>0.05). The results suggest that the TNF-$\alpha$ -308 and -238 promoter polymorphisms are not associated with the development of chronic HBV infection in the Korean population.

Prescribing Patterns of Antivirals for Chronic Hepatitis B (만성 B형간염 진단 환자의 항바이러스제 처방양상)

  • Kong, Hye-Kyung;Sohn, Hyun-Soon;Choi, Kyung-Eob;Kwon, Jin-Won;Shin, Hyun-Taek
    • Korean Journal of Clinical Pharmacy
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    • v.22 no.1
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    • pp.81-86
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    • 2012
  • This study was aimed to examine the prescribing patterns of antivirals in outpatients with chronic hepatitis B (CHB), using National Health Insurance adjudicated claims data (total 1,426,065 claims) dated March 19, 2008 submitted from nationwide healthcare providers to Health Insurance Review and Assessment Service. From the data, there were 2,965 claims with CHB diagnosis (ICD-10 code B18.0 and B18.1), and 44.2% (1,311 claims) of the CHB related claims included antivirals such as lamivudine, clevudine, adefovir and entecavir. Lamivudine, adefovir, clevudine and entecavir shared 54.9%, 19.9%, 13.2% and 11.9%, respectively, among antiviral prescriptions. Adefovir and entecavir 1mg presumed as the 2nd line therapy for HBV resistant cases were shared 23.3% of overall antiviral prescriptions. There were statistically significant difference in prescription patterns according to age and institution type: Lamivudine usage was higher in younger (< 20 years old) and older age group (> 70 years old) than the others (p = 0.016), and adefovir and entecavir, which were relatively newer antivirals, had higher prescription rates in higher level of institutions such as tertiary hospitals than the others (p < 0.001). This study would be of help to make an appropriate drug therapy plan for patients with CHB.

Clinical Experience with Long-term Lamivudine Therapy to Determine the Adequate Duration of Treatment in Children and Adolescents with HBeAg-Negative Chronic Hepatitis B (HBeAg 음성 만성 B형 간염 소아청소년 환자에서 라미부딘의 적절 치료 기간 결정을 위한 장기 치료 경험)

  • Kim, Jung-Mi;Hong, Suk-Jin;Choi, Byung-Ho;Chu, Mi-Ae;Cho, Seung-Man;Choe, Byung-Ho
    • 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.

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