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1993—2002年福州市传染病院入院肝炎病例分型及流行趋势研究
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作者 周天喜 韩荔芬 +2 位作者 吴善群 王枝新 何家鑫 《海峡预防医学杂志》 CAS 2004年第1期40-41,共2页
[目的 ]研究与分析福州市传染病院 10年入院患者各型肝炎的流行趋势。[方法 ]用ELISA方法检测甲~戊型病毒性肝炎 ,并进行统计分析。[结果 ]总病例数逐年上升 ,乙肝病例数逐年增高 ,甲肝病例逐年减少 ,戊肝病例呈波动性变化 ;乙肝、甲... [目的 ]研究与分析福州市传染病院 10年入院患者各型肝炎的流行趋势。[方法 ]用ELISA方法检测甲~戊型病毒性肝炎 ,并进行统计分析。[结果 ]总病例数逐年上升 ,乙肝病例数逐年增高 ,甲肝病例逐年减少 ,戊肝病例呈波动性变化 ;乙肝、甲肝和戊肝 ,占总数的 90 %左右。 [结论 ]肝炎疫情仍然严重 ,原因是多方面的 ;预防与控制的重点在乙肝、甲肝和戊肝。 展开更多
关键词 肝炎 毒性肝炎/甲型 病毒性肝炎/乙型 毒性肝炎/戊型 流行趋势 控制
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Role of Antivirus Therapy in Treatment of Hepatocellular Carcinoma with Chronic Hepatitis B Infection 被引量:1
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作者 程树群 丁光辉 +5 位作者 石洁 郭卫星 赵玉祥 沈丽 梁丽琼 吴孟超 《The Chinese-German Journal of Clinical Oncology》 CAS 2005年第6期330-333,共4页
Objective: To observe the recurrence and prognosis of hepatocellular carcinoma (HCC) patients coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lami... Objective: To observe the recurrence and prognosis of hepatocellular carcinoma (HCC) patients coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lamivudine and thymosin α1 (Tα1) postoperatively. Methods: From Jan. 2000 to Dec. 2003, 70 patients with HCC coexisting chronic hepatitis B infection with active virus replication were prospectively divided into two groups: control group (n=35) received hepatectomy only; treatment group (n=35) received hepatectomy and lamivudine plus Tα1 therapy postoperatively. The suppression of HBV-DNA, HBeAg seroconverted rate, tumor recurrent rate and the median survival for the two groups were observed and calculated. Results: In treatment group and control group, the 2-year HBV-DNA suppression rate was 100% vs. 4% (P=0.0000); HBeAg seroconverted rate was 73.0% vs. 7.5% (P〈0.05); the recurrent rate was 10.0 vs 6.5 months (P=0.0032); the median survival time was 12.5 vs. 6.0 months (P=0.0023), respectively. Conclusion: Antivirus therapy using lamivudine and Tα1 postoperatively may suppress the HBV reaction, delay the recurrent time and prolong the survival for HCC patients coexisting chronic HBV infection with active virus replication. 展开更多
关键词 hepatocellular carcinoma HEPATITIS RECURRENCE antivirus therapy
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Serum concentration of sFas and sFasL in healthy HBsAg carriers,chronic viral hepatitis B and C patients 被引量:7
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作者 Tadeusz Wojciech Lapinski Oksana Kowalczuk +1 位作者 Danuta Prokopowicz Lech Chyczewski 《World Journal of Gastroenterology》 SCIE CAS CSCD 2004年第24期3650-3653,共4页
AIM:To estimate the amount of apoptosis among healthy HBsAg carriers,patients with chronic HBV infection treated wibh lamivudine and patients with chronic HCV infection treated with interferon alpha and ribavirin.Acti... AIM:To estimate the amount of apoptosis among healthy HBsAg carriers,patients with chronic HBV infection treated wibh lamivudine and patients with chronic HCV infection treated with interferon alpha and ribavirin.Activity of apoptosis was evaluated by serum sFas/sFasL concentration measurement. Moreover dependence between apoptosis and HBV-DNA or HCV-RNA levels was studied. METHODS:Eighty-six persons were included into study:34 healthy HBsAg carders,33 patients with chronic HBV infecl^on and 19 patients with chronic HCV infection.Serum levels of sFas/sFasL were measured by ELISA assay.HBV-DNA and HCV-RNA were measured by RT-PCR assay.Levels of sFas/sFasL were determined before and 2 and 12 wk after therapy in patients with chronic hepatitis B and C infection. HBV-DNA or HCV-RNA was detected before treatment and 6 mo after treatment. RESULTS:Twenty-four (71%) healthy HBsAg carders showed HBV-DNA over 10~5/mL,which was comparable to the patients with chronic hepatitis B.independently from HBV-DNA levels, the concentration of sFas among healthy HBsAg carders was comparable to healthy persons.Among patients with chronic hepatitis B and C,the concentration of sFas was significantly higher in comparison to healthy HBsAg carriers and healthy persons.In chronic hepatitis B patients the concentration of sFas was decreased during lamivudine treatment.Among chronic hepatitis C patients the concentration of sFas was increased during IFN alpha and ribavirin treatment,sFasL was not detected in control group.Furbhermore sFasL occurred more frequently in chronic hepatitis C patients in comparison to chronic hepatitis B patients. CONCLUSION:There are no correlations between apoptosis and HBV-DNA levels.However ther is an association between apoptosis and activity of inflammation in patients with chronic HBV infection.Apoptosis can be increased in patients with chronic hepatitis C by effective treatment which may be a result of apoptosis stimulation by IFN-α. 展开更多
关键词 Adolescent Adult Aged Antigens CD95 Apoptosis Biological Markers Carrier State DNA Viral Female Hepatitis B Surface Antigens Hepatitis B Chronic Hepatitis C Chronic Humans LAMIVUDINE Male Membrane Glycoproteins Middle Aged RNA Viral Reverse Transcriptase Inhibitors Solubility
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Development of Novel Therapeutics for Chronic Hepatitis B 被引量:6
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作者 You-hua XIE Ran HONG +2 位作者 Wei LIU Jing LIU Jian-wei ZHAI 《Virologica Sinica》 SCIE CAS CSCD 2010年第4期294-300,共7页
Chronic infection of hepatitis B virus (HBV) presents one of the serious public health challenges worldwide. Current treatment of chronic hepatitis B (CHB) is limited, and is composed of interferon and nucleoside/nucl... Chronic infection of hepatitis B virus (HBV) presents one of the serious public health challenges worldwide. Current treatment of chronic hepatitis B (CHB) is limited, and is composed of interferon and nucleoside/nucleotide reverse transcriptase inhibitors (NRTI). Interferon is poorly tolerated and is only responsive in a small fraction of CHB patients and NRTIs often face the problem of emergence of drug resistance during long-term treatment. The current treatment of CHB can be improved in several ways including genotyping mutations associated with drug resistance before treatment to guide the choice of NRTIs and suitable combinations among NRTIs and interferon. It is important to continue research in the identification of novel therapeutic targets in the life cycle of HBV or in the host immune system to stimulate the development of new antiviral agents and immunotherapies. Several antiviral agents targeting HBV entry, cccDNA, capsid formation, viral morphogenesis and virion secretion, as well as two therapeutic vaccines are currently being evaluated in preclinical studies or in clinical trials to assess their anti-HBV efficacy. 展开更多
关键词 Hepatitis B virus (HBV) TREATMENT Chronic infection ANTIVIRAL
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Replication of clinical hepatitis B virus isolate and its application for selecting antiviral agents for chronic hepatitis B patients 被引量:4
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作者 Yin-Ping Lu Tao Guo +5 位作者 Bao-Ju Wang Ji-Hua Dong Jian-Fang Zhu Zhao Liu Meng-Ji Lu Dong-Liang Yang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第22期3490-3496,共7页
AIM: To establish a cell model harboring replicative clinical hepatitis B virus (HBV) isolates and evaluate its application in individualized selection of anti-HBV agents for chronic hepatitis B (CHB) patients. METHOD... AIM: To establish a cell model harboring replicative clinical hepatitis B virus (HBV) isolates and evaluate its application in individualized selection of anti-HBV agents for chronic hepatitis B (CHB) patients. METHODS: The full-length HBV genomic DNA from 8 CHB patients was amplified by polymerase chain reaction (PCR). All the patients were treated with lamivudine for at least seven months and finally became resistant to lamivudine. The amplified HBV DNA fragments were inserted into pHY106 vectors by Sap Ⅰ?digestion. The recombinant plasmids containing 1.1 copies of HBV genome were transiently transfected into Huh7 cell line, and the levels of HBsAg, HBeAg and intercellular HBV replicative intermediates were determined by ELISA and Southern blot analysis, respectively, with or without lamivudine and adefovir treatment. The antiviral treatment with adefovir was administered to the patients and analyzed in parallel. RESULTS: A total of 25 independent HBV isolateswere obtained from the sera of 8 patients, each patient had at least two isolates. One isolate from each individual was selected and subcloned into pHY106 vector, including 5 isolates with YVDD mutation and 3 isolates with YIDD mutation. All recombinant plasmids harboring HBV isolates were transfected into Huh7 cells. The results indicated that HBV genome carried in HBV replicons of clinical HBV isolates could effectively replicate and express in Huh7 cells. Adefovir, but not lamivudine, inhibited HBV replication both in vitro and in vivo, and in vitro inhibition was dose-dependent. CONCLUSION: The novel method described herein enables individualized selection of anti-HBV agents in clinic and is useful in future studies of antiviral therapy for CHB. 展开更多
关键词 Hepatitis B virus Chronic hepatitis B Hepatitis B virus isolate Antiviral agents
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Durability of viral response after off-treatment in HBeAg positive chronic hepatitis B 被引量:7
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作者 Myeong Jun Song Do Seon Song +8 位作者 Hee Yeon Kim Sun Hong Yoo Si Hyun Bae Jong Young Choi Seung Kew Yoon Yong-Han Paik June Sung Lee Hyun Woong Lee Hyung Joon Kim 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第43期6277-6283,共7页
AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were ad... AIM:To evaluate the durability in hepatitis B e antigen (HBeAg) positive chronic hepatitis B patients who discontinued antiviral treatment. METHODS:A total of 48 HBeAg positive chronic hepatitis B patients who were administered nucleoside analogues and maintained virological response for ≥ 6 mo [hepatitis B virus (HBV) DNA < 300 copies/mL and HBeAg seroconversion] before cessation of treatment were enrolled between February 2007 and January 2010. The criteria for the cessation of the antiviral treatment were defined as follows:(1) achievement of virological response; and (2) duration of consolidation therapy (≥ 6 mo). After treatment cessation, the patients were followed up at 3-6 mo intervals. The primary endpoint was serologic and virologic recurrence rates after withdrawal of antiviral treatment. Serologic recurrence was defined as reappearance of HBeAg positivity after HBeAg seroconversion. Virologic recurrence was defined as an increase in HBV-DNA level > 104 copies/mL after HBeAg seroconversion with previously undetectable HBV-DNA level. RESULTS:During the median follow-up period of 18.2 mo (range:5.1-47.5 mo) after cessation of antiviral treatment, the cumulative serological recurrence rate was 15 % at 12 mo. The median duration between the cessation of antiviral treatment and serologic recurrence was 7.2 mo (range:1.2-10.9 mo). Of the 48 patients with HBeAg positive chronic hepatitis, 20 (41.6%) showed virological recurrence. The cumulative virologic recurrence rates at 12 mo after discontinuing the antiviral agent were 41%. The median duration between off-treatment and virologic recurrence was 7.6 mo (range:4.3-27.1 mo). The mean age of the virological recurrence group was older than that of the non-recurrence group (46.7 ± 12.1 years vs 38.8 ± 12.7 years, respectively; P = 0.022). Age (> 40 years) and the duration of consolidation treatment (≥ 15 mo) were significant predictive factors for offtreatment durability in the multivariate analysis [P = 0.049, relative risk (RR) 0.31, 95% CI (0.096-0.998) and P = 0.005, RR 11.29, 95% CI (2.054-65.12), respectively]. Patients with age (≤ 40 years) who received consolidation treatment (≥ 15 mo) significantly showed durability in HBeAg positive chronic hepatitis B patients (P = 0.014). These results suggest that additional treatment for more than 15 mo after HBeAg seroconversion in patients who are ≤ 40 years old may be beneficial in providing a sustained virological response. CONCLUSION:Our data suggest that HBeAg seroconversion is an imperfect end point in antiviral treatment. Long-term consolidation treatment (≥ 15 mo) in younger patients is important for producing better prognosis in HBeAg positive chronic hepatitis B. 展开更多
关键词 DURABILITY SEROCONVERSION Chronic hepatitis B Hepatitis B e antigen positive RECURRENCE CONSOLIDATION
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An overview of occult hepatitis B virus infection 被引量:22
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作者 Zeinab Nabil Ahmed Said 《World Journal of Gastroenterology》 SCIE CAS CSCD 2011年第15期1927-1938,共12页
Occult hepatitis B virus (HBV) infection (OBI), alternatively defined as occult hepatitis B (OHB), is a challenging clinical entity. It is recognized by two main characteristics: absence of HBsAg, and low viral replic... Occult hepatitis B virus (HBV) infection (OBI), alternatively defined as occult hepatitis B (OHB), is a challenging clinical entity. It is recognized by two main characteristics: absence of HBsAg, and low viral replication. The previous two decades have witnessed a remarkable progress in our understanding of OBI and its clinical implications. Appropriate diagnostic techniques must be adopted. Sensitive HBV DNA amplification assay is the gold standard assay for detection of OBI. Viral as well as host factors are implicated in the pathogenesis of OBI. However, published data reporting the infectivity of OBI by transfusion are limited. Several aspects including OBI transmission, infectivity and its relation to the development of chronic liver diseases and hepatocellular carcinoma have to be resolved. The aim of the present review is to highlight recent data on OBI with a focus on its virological diagnosis and clinical outcome. 展开更多
关键词 Hepatitis B virus Occult infection Occult hepatitis B virus infection Occult hepatitis B Chronic liver disease Hepatocellular carcinoma Hepatitis B surface antigen
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Interplay between hepatitis B virus and the innate immune responses:implications for new therapeutic strategies 被引量:9
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作者 Jieliang Chen Zhenghong Yuan 《Virologica Sinica》 SCIE CAS CSCD 2014年第1期17-24,共8页
Hepatitis B virus(HBV) infection is still a worldwide health problem;however,the current antiviral therapies for chronic hepatitis B are limited in efficacy.The outcome of HBV infection is thought to be the result of ... Hepatitis B virus(HBV) infection is still a worldwide health problem;however,the current antiviral therapies for chronic hepatitis B are limited in efficacy.The outcome of HBV infection is thought to be the result of complex interactions between the HBV and the host immune system.While the role of the adaptive immune responses in the resolution of HBV infection has been well characterized,the contribution of innate immune mechanisms remains elusive until recent evidence implicates that HBV appears to activate the innate immune response and this response is important for controlling HBV infection.Here,we review our current understanding of innate immune responses to HBV infection and the multifaceted evasion by the virus and discuss the potential strategies to combat chronic HBV infection via induction and restoration of host innate antiviral responses. 展开更多
关键词 HBV innate immunity viral evasion INTERFERON antiviral approaches
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Relationship between HLA-DR gene polymorphisms and outcomes of hepatitis B viral infections:A meta-analysis 被引量:11
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作者 Ze-Hui Yan Yi Fan +3 位作者 Xiao-Hong Wang Qing Mao Guo-Hong Deng Yu-Ming Wang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第24期3119-3128,共10页
AIM:To assess the rigorous relationship between human leukocyte antigens(HLA)-DR alleles and outcomes of hepatitis B virus(HBV) infections by means of metaanalysis.METHODS:Medline/PubMed,EMBASE,CNKI and VIP were searc... AIM:To assess the rigorous relationship between human leukocyte antigens(HLA)-DR alleles and outcomes of hepatitis B virus(HBV) infections by means of metaanalysis.METHODS:Medline/PubMed,EMBASE,CNKI and VIP were searched to identify relevant studies.Study quality was evaluated using the Newcastle-Ottawa Scale.Odds ratios(OR) and 95% confidence interval(95% CI) were pooled using Stata 11.0.Subgroup analyses were performed by ethnicity.Heterogeneity and publication bias analyses were performed to validate the credibility.RESULTS:A total of 2609 patients with chronic hepatitis B and 2606 controls spontaneously recovering from prior HBV infection were included.Meta-analysis showed that HLA-DR*04(OR = 0.72,95% CI:0.60-0.85) and DR*13(OR = 0.27,95% CI:0.19-0.37) alleles were significantly associated with HBV clearance while patients carrying HLA-DR*03(OR = 1.47,95% CI:1.16-1.87) or DR*07(OR = 1.59,95% CI:1.24-2.03) alleles had a significantly increased risk of chronic HBV persistence.For the HLA-DR*01 polymorphism,a significantly association with HBV clearance was found in Chinese Han group(OR = 0.48,95% CI:0.26-0.86),but not found in other ethnic groups(P = 0.191).For other polymorphisms,no association with the HBV infection outcome was found.CONCLUSION:HLA-DR*04 and DR*13 alleles may be the protective factors for HBV clearance and HLADR*03,and DR*07 alleles may be the risk factors for HBV persistence. 展开更多
关键词 Hepatitis B virus Human leukocyte anti-gens META-ANALYSIS POLYMORPHISM
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New therapeutic vaccination strategies for the treatment of chronic hepatitis B 被引量:9
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作者 Jia Liu Anna Kosinska +1 位作者 Mengji Lu Michael Roggendorf 《Virologica Sinica》 SCIE CAS CSCD 2014年第1期10-16,共7页
Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in o... Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in only about 30%patients and is associated with side effects.Most patients receiving nucleot(s)ide analogue treatment do not establish long-term,durable control of Infection and have rebounding viremia after cessation of therapy.Thus,novel therapy strategies are necessary to achieve the induction of potent and durable antiviral immune responses of the patients which can maintain long-term control of viral replication.Therapeutic vaccination of HBV carriers is a promising strategy for the control of hepatitis B.Here the authors review new therapeutic vaccination strategies to treat chronic hepatitis B which may be introduced for patient treatment in the future. 展开更多
关键词 hepatitis B virus woodchuck hepatitis virus therapeutic vaccination IMMUNOMODULATION programmed death-1
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HBeAg negative serological status and low viral replication levels characterize chronic hepatitis B virus-infected women at reproductive age in Greece: A one-year prospective single center study 被引量:3
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作者 Ioannis S. Elefsiniotis Irene Glynou +5 位作者 Ioanna Magaziotou Konstantinos D. Pantazis Nikolaos V. Fotos Hero Brokalaki Helen Kada George Saroglou 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第31期4879-4882,共4页
AIM: To evaluate the seroprevalence of hepatitis B surface antigen (HBsAg) in 13 581 women at reproductive age and the hepatitis B e antigen (HBeAg)/anti-HBe status as well as serum hepatitis B virus (HBV)-DNA ... AIM: To evaluate the seroprevalence of hepatitis B surface antigen (HBsAg) in 13 581 women at reproductive age and the hepatitis B e antigen (HBeAg)/anti-HBe status as well as serum hepatitis B virus (HBV)-DNA levels in a subgroup of HBsAg(+) pregnant women at labor in Greece. METHODS: Serological markers were detected using enzyme immunoassays. Serum HBV-DNA was determined by a sensitive quantitative PCR assay. Statistical analysis of data was based on parametric methodology. RESULTS: Overall, 1.156% of women were HBsAg(+) and the majority of them (71.3%) were Albanian. The prevalence of HBsAg was 5.1% in Albanian women, 4.2% in Asian women and 1.14% in women from Eastern European countries. The prevalence of HBsAg in African (0.36%) and Greek women (0.29%) was very low. Only 4.45% of HBsAg (+) women were also HBeAg(+) whereas the vast majority of them were HBeAg(-)/anti-HBe(+). Undetectable levels of viremia (〈200 copies/mL) were observed in 32.26% of pregnant women at labor and 29.03% exhibited extremely low levels of viral replication (〈400 copies/mL). Only two pregnant women exhibited extremely high serum HBV- DNA levels (〉10 000 000 copies/mL), whereas 32.26% exhibited HBV-DNA levels between 1 500 and 40 000 copies/mL. CONCLUSION: The overall prevalence of HBsAg is relatively low among women at reproductive age in Greece but is higher enough among specific populations. The HBeAg(-)/anti-HBe(+) serological status and the extremely low or even undetectable viral replicative status in the majority/of HBsAg(+) women of our study population, suggestthat only a small proportion of HBsAg(+) women in Greece exhibit a high risk for vertical transmission of the infection. 展开更多
关键词 Hepatitis B Reproductive age Verticaltransmission HBEAG HBV-DNA
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Relationship between IFN-γ gene polymorphism and susceptibility to intrauterine HBV infection 被引量:14
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作者 Hui Yu Qi-Rong Zhu Shao-Qing Gu Lin-E Fei 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第18期2928-2931,共4页
AIM: To explore the susceptibility of children to intrauterine HBV infection by studying the relationship between IFN-γ gene polymorphism, including IFN-γ+874A/T single nucleotide polymorphism(SNP) and CA repeat... AIM: To explore the susceptibility of children to intrauterine HBV infection by studying the relationship between IFN-γ gene polymorphism, including IFN-γ+874A/T single nucleotide polymorphism(SNP) and CA repeat microsatellite polymorphism and intrauterine HBV infection. METHODS: A TaqMan fluorescence polymerase chain reaction in the IFN-γ+874A/T single nucleotide polymorphism was tested in the intrauterine HBV infection group(group Ⅰ) and the normal immune children group(group Ⅱ). Capillary electrophoresis was performed in the above two groups to assay the IFN-γ, CA repeat microsatellite polymorphism. RESULTS: Frequencies of AA, AT and TT genotypes were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection group, and 45.2%, 30.1% and 24.7% in the normal immune children group, respectively. A significant difference was found in the frequency distribution of IFN-γ+874 genotype between the two groups (x^2 = 5.102, P = 0.02389). In the intrauterine HBV infection group the AA genotype was more common than in the normal immune group. Frequency of IFN-γ+874A allele was 77.17% in the intrauterine HBV infection group, and 60.27% in the normal immune children group. In the intrauterine HBV infection group the IFN-γ+874A allele was more common than in normal immune group. A significant difference was found in the frequency distribution between the two groups (x^2= 7.238, P= 0.02389, OR = 2.228, 95% CI = 1.244-3.992). (CA12)^+/(CA12)^+ of IFN-γ CA microsatellite polymorphism was 11.90% in the intrauterine HBV infection group and 26.47% in the normal immune children group. A significant difference was found in the frequency distribution between the two groups (x^2 = 5.64, P = 0.0176). Frequency of IFN-γ CA repeat was 25% in the intrauterine HBV infection group and 43.38% in the normal immune children group. The frequency of IFN-γ CA repeat was less in the intrauterine HBV infection group than in normal immune group. A significant difference was found in the frequency distribution between the two groups (x^2 = 7.548, P= 0.0060). CONCLUSION: There is a relationship between IFN-γ+874A/T SNP and intrauterine HBV infection as well as between IFN-γ CA microsatellite polymorphism and intrauterine HBV infection. IFN-γ gene polymorphism might be important in determining individual's susceptibility to intrauterine HBV infection. 展开更多
关键词 INTERFERON-Γ Gene polymorphism Hepatitis B virus INTRAUTERINE
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Mechanism of T cell hyporesponsiveness to HBcAg is associated with regulatory T cells in chronic hepatitis B 被引量:16
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作者 Yasuteru Kondo Koju Kobayashi +5 位作者 Yoshiyuki Ueno Masaaki Shiina Hirofumi Niitsuma Noriatsu Kanno Tomoo Kobayashi Tooru Shimosegawa 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第27期4310-4317,共8页
AIM: To study the mechanisms of hyporesponsiveness of HBV-specific CD4^+ T cells by testing TH1 and TH2 commitment and regulatory T cells. METHODS: Nine patients with chronic hepatitis B were enrolled. Peripheral b... AIM: To study the mechanisms of hyporesponsiveness of HBV-specific CD4^+ T cells by testing TH1 and TH2 commitment and regulatory T cells. METHODS: Nine patients with chronic hepatitis B were enrolled. Peripheral blood mononuclear cells were stimulated with HBcAg or HBsAg to evaluate their potential to commit to TH1 and TH2 differentiation. HBcAg-specific activity of regulatory T cells was evaluated by staining with antibodies to CD4, CD25, CTLA-4 and interleukin-10. The role of regulatory T cells was further assessed by treatment with anti-interleukin-10 antibody and depletion of CD4^+CD25^+ cells. RESULTS: Level of mRNAs for T-bet, IL-12R β2 and IL-4 was significantly lower in the patients than in healthy subjects with HBcAg stimulation. Although populations of CD4^+CD25^highCTLA-4^+ T cells were not different between the patients and healthy subjects, IL-10 secreting cells were found in CD4^+ cells and CD4^+CD25^+ cells in the patients in response to HBcAg, and they were not found in cells which were stimulated with HBsAg. Addition of anti-IL-10 antibody recovered the amount of HBcAgspecific TH1 antibody compared with control antibody (P 〈 0.01, 0.34% ± 0.12% vs 0.15% ± 0.04%). Deletion of CD4^+CD25^+ T cells increased the amount of HBcAgspecific TH1 antibody when compared with lymphoo/tes reconstituted using regulatory T cells (P 〈 0.01, 0.03% ± 0.02% vs 0.18% ± 0.05%).CONCLUSION: The results indicate that the mechanism of T cell hyporesponsiveness to HBcAg includes activation of HBcAg-induced regulatory T cells in contrast to an increase in TH2-committed cells in response to HBsAg. 展开更多
关键词 Hepatitis B virus Regulatory T cells IL-10 FOXP3 TH1
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Horizontal transmission of hepatitis B virus in children with chronic hepatitis B 被引量:2
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作者 Tumay Doganci Gulnar Uysal +3 位作者 Tayfun Kir Arzu Bakirtas Necdet Kuyucu Levent Doganci 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第3期418-420,共3页
AIM: To determine the possible routes of intrafamilial transmission pattern in pediatrie cases of chronic hepatitis B virus (HBV) infection. METHODS: In this descriptive retrospective study, 302 children with chronic ... AIM: To determine the possible routes of intrafamilial transmission pattern in pediatrie cases of chronic hepatitis B virus (HBV) infection. METHODS: In this descriptive retrospective study, 302 children with chronic HBV infection from 251 families and their parents attending the Social Security Children's Hospital and Doctor Sami Ulus Children's Hopsital in Ankara between December 1998 and May 2000, were enrolled in. Screenings and diagnosis of chronic HBV infections were established according to the Consensus 2000. RESULTS: In the studied 302 children with chronic HBV infection, mothers of 38% and fathers of 23% were HBsAg positive. The HBsAg positivity in at least two siblings of the same family was 61% when both parents were HBsAg positive. CONCLUSION: It is well known that hon'zontal transmission is quite common in countries where Hepatitis B Virus is moderately endemic. To our best knowledge, this is the largest series observed regarding the horizontal transmission in pediatrie chronic HBV infection in Turkey. It is necessary to expand the preventive programs to target not only the newborn period but also all stages of childhood. 展开更多
关键词 Chronic hepatitis B Horizontal transmission
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Existence and significance of hepatitis B virus DNA in kidneys of IgA nephropathy 被引量:11
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作者 Nian-SongWang Zhao-LongWu +1 位作者 Yue-EZhang Lu-TanLiao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第5期712-716,共5页
AIM: To investigate the existence and significance of hepatitis B virus (HBV) DNA in the pathogenesis of IgA nephropathy(IgAN).METHODS: Fifty cases of IgAN with HBV antigenaemia and/or hepatitis B virus antigens (HBAg... AIM: To investigate the existence and significance of hepatitis B virus (HBV) DNA in the pathogenesis of IgA nephropathy(IgAN).METHODS: Fifty cases of IgAN with HBV antigenaemia and/or hepatitis B virus antigens (HBAg, or HBsAg, HBcAg)detected by immunohistochemistry in renal tissues were enrolled in our study. The distribution and localization of HBV DNA were observed using in situ hybridization.Southern blot analysis was performed to reveal the state of renal HBV DNA.RESULTS: Among the 50 patients with IgAN, HBs antigenemia was detected in 17 patients (34%). HBAg in renal tissues was detected in 48 patients (96%), the positive rate of HBAg, HBsAg, and HBcAg was 82% (41/50), 58% (29/50),and 42% (21/50) in glomeruli, respectively; and was 94%(47/50), 56% (28/50) and 78% (39/50) in tubular epithelia,respectively. Positive HBV DNA was detected in 72% (36/50)and 82% (41/50) cases in tubular epithelia and glomeruli respectively by in Situ hybridization, and the positive signals were localized in the nuclei of tubular epithelial cells and glomerular mesangial cells as well as infiltrated interstitial lymphocytes. Moreover, 68% (34/50) cases were proved to be HBV DNA positive by Southern blot analysis, and all were the integrated form.CONCLUSION: HBV infection might play an important role in occurrence and progress of IgAN. In addition to humoral immune damages mediated by HBAg-HBAb immune complex,renal tissues of some IgAN are directly infected with HBV and express HBAg in situ, and the cellular mechanism mediated by HBV originating from renal cells in situ may also be involved in the pathogenesis of IgAN. 展开更多
关键词 Hepatitis B virus DNA IgA nephropathy
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Relationship of human leukocyte antigen class II genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients 被引量:28
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作者 Yong-Nian Han Jin-Long Yang Shui-Gen Zheng Qun Tang Wei Zhu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第36期5721-5724,共4页
AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients. METHODS: Low... AIM: To study the relationship of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon (IFN) in HBV-infected patients. METHODS: Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B (CHB) and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai. Among CHB patients, 35 were treated with IFNα-1b for 24 wk. RESULTS: The frequencies of HLA-DRBI*06, DRBI*08 and DRB1*16 alleles in 72 patients were higher than in 200 healthy people (2.08% vs0%, OR = 3.837, P= 0.018; 11.11% vs5.50%, OR = 2.148, P= 0.034; and 6.94% vs 3.00%, OR = 0.625, P = 0.049, respectively); whereas that of DRBI*07 allele was lower (2.78% vs 7.75%, OR = 0.340, P= 0.046). The frequency of HLA-DRBI* 14 allele was higher in 11 responders to IFN compared with 24 non-responders (18.18% vs2.08%, OR = 10.444, P = 0.031), whereas that of DQBI*07 allele was inverse (9.09% vs37.50%, OR = 0.167, P= 0.021). CONCLUSION: The polymorphism of HLA class II may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRBI*06, DRBI*08, and DRB1*16 may be associated with chronicity of HBV infection, HLA-DRBI*07 with protection against HBV infection, and HLA-DRB1*14 allele may be associated with a high rate of the response of CHB patients to IFN treatment. Compared with other HLA-DQB1 alleles, HLA-DQBI*07 may be associated with low response rate to IFN. 2005 The WJG Press and Elsevier Inc. All rights reserved 展开更多
关键词 Hepatitis B Human leukocyte antigens Geneticsusceptibility INTERFERON
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Polymorphisms of some cytokines and chronic hepatitis B and C virus infection 被引量:16
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作者 Qiu-Ju Gao Dian-Wu Liu +5 位作者 Shi-Yong Zhang Min Jia Li-Min Wang Li-Hong Wu Shu-Yun Wang Li-Xin Tong 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第44期5610-5619,共10页
AIM: To study the relationship between the polymorphisms in some cytokines and the outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. METHODS: Samples were obtained from 203 patients infec... AIM: To study the relationship between the polymorphisms in some cytokines and the outcome of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. METHODS: Samples were obtained from 203 patients infected with HBV and/or HCV while donating plasma in 1987, and 74 controls were obtained from a rural area of North China. Antibodies to HBV or HCV antigens were detected by enzyme-linked imrnunoassay. The presence of viral particles in the serum was determined by nested reverse-transcriptase polymerase chain reaction (PCR). Hepatocellular injury, as revealed by alanine aminotransferase (ALT) and aspartate aminotransferase level, was detected by a Beckman LX-20 analyzer. DNA was extracted from blood cells. Then, the single nucleotide polymorphisms of IL-2-330, IFN-γ+874, IL-10-1082/-592 and IL-4-589 were investigated by restriction fragment length polymorphism-PCR or sequence specific primer-PCR.RESULTS: Persistent infection with HBV, HCV, and HBV/HCV coinfection was associated with IL-2-330 TT genotype and T allele, IFN-γ+874 AA genotype, and IL-10-1082 AA genotype. The clinical outcome of HBV and/or HCV infection was associated with IL-2-330 TT genotype and T allele, IFN-γ+874 AA genotype, and IL-10-1082 AA genotype. IL-2-330 GG genotype frequency showed a negative correlation with clinical progression, IL-10-1082 AA genotype frequency showed a positive correlation and IL-10-1082 AG genotype frequency showed a negative correlation with clinical progression. HCV RNA positive expression was associated with IL-10-1082 AA genotype and the A allele frequency. Abnormal serum ALT level was associated with IL-10-592 AC genotype frequency and IL-4-589 CC genotype, CT genotype, and the C allele. CONCLUSION: These results suggest that polymorphisms in some cytokine genes influence persistent HBV and HCV infection, clinical outcome, HCV replication, and liver damage. 展开更多
关键词 Hepatitis B Hepatitis C Single nucleotide polymorphism Disease susceptibility Outcome studies CYTOKINES
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Inhibition of hepatitis B virus surface antigen expression by small hairpin RNA in vitro 被引量:8
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作者 Zheng-GangYang ZhiChen QinNi NingXu Jun-BinShao Hang-PingYao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第4期498-502,共5页
AIM: To explore the anti-hepatitis B virus effect of RNA interference (RNAi) using small hairpin RNA (shRNA)expression vector.METHODS: Hepatitis B virus surface antigen green fluorescent protein (HBs-GFP) fusion vecto... AIM: To explore the anti-hepatitis B virus effect of RNA interference (RNAi) using small hairpin RNA (shRNA)expression vector.METHODS: Hepatitis B virus surface antigen green fluorescent protein (HBs-GFP) fusion vector and shRNA expression vectors were constructed and cotransfected transiently into HepG2 cells. mRNAs extracted from HepG2 cells were detected by real-time PCR. Fluorescence of HBs-GFP protein was detected by fluorescence-activated cell sorting (FACS). The effective shRNA expression vector was transfected into HepG2.2.15 cells. HBsAg and HBeAg in HepG2.2.15 cells were analyzed by radioimmunoassay (RIA) method.RESULTS: FACS revealed that shRNA targeting at HBsAg reduced the GFP signal by 56% compared to the control.Real-time PCR showed that HBs-GFP mRNA extracted from HepG2 cells cotransfected with pAVU6+27 and HBs-GFP expression plasmids decreased by 90% compared to the empty vector control. The expressions of HBsAg and HBeAg were also inhibited by 43% and 64%, respectively.CONCLUSION: RNAi using shRNA expression vector can inhibit the expression of HBsAg, providing a fresh approach to screening the efficient small interfering RNAs (siRNAs). 展开更多
关键词 Hepatitis B Surface Antigens Small hairpin RNA RNA interference Gene expression
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Anti-HBV activity of TRL mediated by recombinant adenovirus 被引量:2
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作者 Wei-DongGong YaZhao +3 位作者 JunYi JinDing JunLiu Cai-FangXue 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第17期2574-2578,共5页
AIM:To investigate the inhibitive effect of hepatitis B virus (HBV)-TRL on HBV replication. METHODS: Based on previously constructed pcDNA3.1 (-)/TRL, TR, TRmut, HBV core protein (HBVc) and hEDN, interest gene sequenc... AIM:To investigate the inhibitive effect of hepatitis B virus (HBV)-TRL on HBV replication. METHODS: Based on previously constructed pcDNA3.1 (-)/TRL, TR, TRmut, HBV core protein (HBVc) and hEDN, interest gene sequences TRL, TR, HBVc and hEDN were inserted into adenovirus shuttle plasmid pDC316 respectively and co-transfected HEK293 cells with rescue plasmid pBHGIox(delta)El,3Cre to acquire RAd/TRL, TR, HBVc and hEDN. And then RAds were identified, amplified and the titers in HEK293 cells were determined. RAd/TRL and TR were named as the experimental groups, and others were control ones. After HepG2.2.15 cells were infected, RAd/TRL expression was identified by indirect immunofluorescence staining. Supernatant HBV-DNA content was determined by fluorescent quantification PCR. Meanwhile, metabolism of HepG2.2.15 cells was evaluated by MTT colorimetry. RESULTS: RAd vectors with distinct interest gene sequence were successfully constructed. Effective expression of RAd/TRL in HepG2.2.15 cells resulted in a significant decrease of supernatant HBV-DNA content compared to RAd/TR (0.63±0.14 vs1.60±0.47, P= 0.0266, <0.05) and other control groups (0.63±0.14 vs8.50±2.78,8.25±2.26, 8.25±2.29, 8.50±1.51, 8.57±1.63, P<0.01). MTT assay suggested that there were no significant differences in cell metabolic activity between groups (P>0.05). CONCLUSION: The construction and expression of RAd/TRL has been achieved and it could inhibit HBV replication successfully, which has laid the foundation for further research on anti-HBV activity in vivo. 展开更多
关键词 HBV HBV-TRL
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Interferon β-1a alone or in combination with ribavirin: A randomized trial to compare efficacy and safety in chronic hepatitis C 被引量:1
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作者 Rinaldo Pellicano Antonio Craxì +12 位作者 Piero Luigi Almasio Mario Valenza Giovanna Venezia Alfredo Alberti Silvia Boccato Luigi Demelia Orazio Sorbello Antonino Picciotto Francesco Torre Gaetano Ideo Carlo Cattaneo Mara Berrutti Mario Rizzetto 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第29期4484-4489,共6页
AIM: To compare the efficacy and safety of recombinant human IFN β-la alone or in combination with ribavirin in treatment-naive subjects with chronic hepatitis C. METHODS: Open, randomized trial was performed in 6 ... AIM: To compare the efficacy and safety of recombinant human IFN β-la alone or in combination with ribavirin in treatment-naive subjects with chronic hepatitis C. METHODS: Open, randomized trial was performed in 6 Italian tertiary centers: 102 of the 108 patients screened were randomized to receive 6 MIU of recombinant human IFN β-la subcutaneously daily for 24 wk, alone (Group 1, n = 51) or in combination with ribavirin 1 000 to 1 200 mg/d (Group 2, n = 51). RESULTS: The end-of-treatment virologic response rate was 29.4% in Group 1 and 41.2% in Group 2 (nonsignificant). Twenty-four weeks after stopping therapy, sustained virologic response rate was 21.6% in Group 1 and 27.4% in Group 2 (non-significant). All subjects in Group 1 completed treatment, while two subjects in Group 2 stopped therapy due to treatment-related adverse events. CONCLUSION: Recombinant human IFN β-la, alone or in combination with ribavirin, has an excellent safety profile and, may represent an alternative for chronic hepatitis C patients who are unable to tolerate pegylated α-interferon. 展开更多
关键词 Chronic hepatitis C IFN β-1a RIBAVIRIN
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