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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 于明暉(Ming-Whei Yu) | |
dc.contributor.author | Szu-Yu Lu | en |
dc.contributor.author | 盧思宇 | zh_TW |
dc.date.accessioned | 2021-06-07T18:07:23Z | - |
dc.date.copyright | 2012-09-17 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2012-07-20 | |
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Boni C, Fisicaro P, Valdatta C, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. J Virol 2007;81(8):4215-25. 45. Rosenberg W. Mechanisms of immune escape in viral hepatitis. Gut 1999;44(5):759-64. 46. Huang CF, Lin SS, Ho YC, et al. The immune response induced by hepatitis B virus principal antigens. Cell Mol Immunol 2006;3(2):97-106. 47. Bertoletti A, Gehring AJ. The immune response during hepatitis B virus infection. J Gen Virol 2006;87(Pt 6):1439-49. 48. Naoumov NV, Eddleston AL. Host immune response and variations in the virus genome: pathogenesis of liver damage caused by hepatitis B virus. Gut 1994;35(8):1013-7. 49. Rehermann B, Pasquinelli C, Mosier SM, et al. Hepatitis B virus (HBV) sequence variation of cytotoxic T lymphocyte epitopes is not common in patients with chronic HBV infection. J Clin Invest 1995;96(3):1527-34. 50. Maman Y, Blancher A, Benichou J, et al. Immune-induced evolutionary selection focused on a single reading frame in overlapping hepatitis B virus proteins. J Virol 2011;85(9):4558-66. 51. Rehermann B, Fowler P, Sidney J, et al. The cytotoxic T lymphocyte response to multiple hepatitis B virus polymerase epitopes during and after acute viral hepatitis. J Exp Med 1995;181(3):1047-58. 52. Bock CT, Tillmann HL, Torresi J, et al. Selection of hepatitis B virus polymerase mutants with enhanced replication by lamivudine treatment after liver transplantation. Gastroenterology 2002;122(2):264-73. 53. Cuestas ML, Mathet VL, Oubina JR, et al. Drug delivery systems and liver targeting for the improved pharmacotherapy of the hepatitis B virus (HBV) infection. Pharm Res 2010;27(7):1184-202. 54. Depla E, Van der Aa A, Livingston BD, et al. Rational design of a multiepitope vaccine encoding T-lymphocyte epitopes for treatment of chronic hepatitis B virus infections. J Virol 2008;82(1):435-50. 55. Ling R, Mutimer D, Ahmed M, et al. Selection of mutations in the hepatitis B virus polymerase during therapy of transplant recipients with lamivudine. Hepatology 1996;24(3):711-3. 56. Lok AS, Heathcote EJ, Hoofnagle JH. Management of hepatitis B: 2000--summary of a workshop. Gastroenterology 2001;120(7):1828-53. 57. Perrillo RP. Acute flares in chronic hepatitis B: the natural and unnatural history of an immunologically mediated liver disease. Gastroenterology 2001;120(4):1009-22. 58. Shindo M, Di Bisceglie AM, Hoofnagle JH. Acute exacerbation of liver disease during interferon alfa therapy for chronic hepatitis C. Gastroenterology 1992;102(4 Pt 1):1406-8. 59. Shiina S, Fujino H, Uta Y, et al. Relationship of HBsAg subtypes with HBeAg/anti-HBe status and chronic liver disease. Part I: Analysis of 1744 HBsAg carriers. Am J Gastroenterol 1991;86(7):866-71. 60. Orito E, Mizokami M, Sakugawa H, et al. A case-control study for clinical and molecular biological differences between hepatitis B viruses of genotypes B and C. Japan HBV Genotype Research Group. Hepatology 2001;33(1):218-23. 61. Kao JH, Chen PJ, Lai MY, et al. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 2000;118(3):554-9. 62. Wai CT, Chu CJ, Hussain M, et al. HBV genotype B is associated with better response to interferon therapy in HBeAg(+) chronic hepatitis than genotype C. Hepatology 2002;36(6):1425-30. 63. Chu CJ, Hussain M, Lok AS. Hepatitis B virus genotype B is associated with earlier HBeAg seroconversion compared with hepatitis B virus genotype C. Gastroenterology 2002;122(7):1756-62. 64. Okamoto H, Tsuda F, Akahane Y, et al. Hepatitis B virus with mutations in the core promoter for an e antigen-negative phenotype in carriers with antibody to e antigen. J Virol 1994;68(12):8102-10. 65. Brunetto MR, Giarin MM, Oliveri F, et al. Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis. Proc Natl Acad Sci U S A 1991;88(10):4186-90. 66. Papatheodoridis GV, Hadziyannis SJ. Diagnosis and management of pre-core mutant chronic hepatitis B. J Viral Hepat 2001;8(5):311-21. 67. Desombere I, Gijbels Y, Verwulgen A, et al. Characterization of the T cell recognition of hepatitis B surface antigen (HBsAg) by good and poor responders to hepatitis B vaccines. Clin Exp Immunol 2000;122(3):390-9. 68. Rodriguez-Frias F, Tabernero D, Quer J, et al. Ultra-deep pyrosequencing detects conserved genomic sites and quantifies linkage of drug-resistant amino Acid changes in the hepatitis B virus genome. PLoS One 2012;7(5):e37874. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16266 | - |
dc.description.abstract | 背景:血清丙氨酸轉胺酶在 B 型肝炎病毒慢性感染期間可能會產生波動,免疫抗原決定位上之胺基酸多型性可能與宿主免疫反應改變相關,本研究針對多個時間點之病毒抗原決定位序列變異與急性發作 (acute exacerbation,AE)之相關性,於慢性 HBV 帶原者中進行病毒全基因體序列分析研究。
材料與方法:研究對象自長期病毒量研究世代中選取 1143 位 HBsAg 陽性且大於 30 歲男性個案,研究對象於收案基線無癌症發生,自 1989 至 1992 年間約每半年至一年追蹤檢查其腹部超音波、肝功能、收取血液檢體並進行其他生化檢查,直到 2006 年為止之收案資料將與全國癌症登記及死亡登記檔連結。 由收案之初即具有序列資料,共 52 急性發作個案(追蹤期間 ALT 峰值≧120 IU/L)中隨機選取追蹤期間 ALT 皆正常之對照組。對照組配對收案年齡(三年內)、HBV 基因型與採檢時間。以 Sanger 定序方法進行全基因體序列分析基線、基線後第一時間點、峰值與峰值後第一時間點等四個時間點。 HBV 基因型則以 MEGA 5.05 軟體建構演化樹作為分類依據 , 勝算比與 95 %信賴區間以廣義線性模式進行運算而得。 結果:本研究發現在不同基因型間具有不同的抗原決定位胺基酸多型性。並搜尋免疫抗原決定位資料庫,找出四個胺基酸變異與急性發作相關之抗原決定位,包含 P 基因區之 RHYLHTLWKAGILYK (OR=0.227, 95%CI=0.05-0.94)、LHLYSHPIILGFRKI (OR=4.8413, 95%CI=1.02-22.9)與 FLLSLGIHL (OR=0.2634, 95%CI=0.08-0.84) ,以及 S 基因區之 FWGPSLYNILSPFMPL (OR=0.2963, 95%CI=0.11-0.79)。此四個抗原決定位胺基酸是否變異與病毒量、抽菸以及 e 抗原具有邊緣性顯著相關,且觀察到在 AE 個案中抗原決定位變異並未隨時間產生改變。 結論: HBV 之聚合酶基因區與表面基因區內的抗原決定位中特定胺基酸多型性可能與急性發作的進程相關。 | zh_TW |
dc.description.abstract | Background: Serum alanine aminotransferase (ALT) may fluctuate during chronic infection of hepatitis B virus (HBV). Amino acid polymorphism in immune epitope can alter host immune response. We aimed to assess the temporal association between viral epitope sequence variants and the occurrence of acute exacerbation (AE) among chronic HBV carriers through full-length sequence analysis.
Methods: Study subjects were obtained from an existing longitudinal viral-load cohort study involving a total of 1143 male HBsAg carriers aged ≥30 years old, who were originally free of cancer at recruitment between 1989 and 1992 and followed by annual clinical evaluation through abdominal ultrasonography and liver biochemistry test and data linkage to the computerized database of national cancer and death registry until Dec. 31, 2006.A total of 52 AE case (ALT peak ≧120 IU/L) with available sequence data at baseline were identified. For each case subject, one control was drawn at random from subjects with normal ALT level. Control subjects were selected to match cases on age (within 3 years) at recruitment, HBV genotype, and blood collection time during follow-up. Full-length HBV genome sequences were analyzed by Sanger sequencing method at three time point, baseline, ALT peak and after ALT peak. HBV genotypes were determined through phylogenetic trees constructed by using Mega 5.05 software. Odds ratios (ORs) and confidence intervals (CIs) were generated by generalized estimating equations. Result: We found different patterns of epitope amino acid polymorphisms between genotypes. By searching immune epitope database, we identified four epitopes amino acid variants were associated with the occurrence of AE, including RHYLHTLWKAGILYK (OR=0.227, 95%CI=0.05-0.94), LHLYSHPIILGFRKI (OR=4.8413, 95%CI=1.02-22.9), and FLLSLGIHL (OR=0.2634, 95%CI=0.08-0.84) in polymerase gene region and FWGPSLYNILSPFMPL (OR=0.2963, 95%CI=0.11-0.79) in surface gene region. The emergences of these four epitope amino acid variants were marginally significant with any other variables, including viral load, smoking and HBeAg. Moreover, those epitope variants did not change over time among AE case. Conclusion: Certain amino acid polymorphism embedded in epitopes in the polymerase and surface genes of HBV may play some role in the indication of acute exacerbation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-07T18:07:23Z (GMT). No. of bitstreams: 1 ntu-101-R99849002-1.pdf: 1223049 bytes, checksum: 1a8936e31b8fc5c30bc23b19f5ec07bf (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | 目錄
中文摘要 i 英文摘要 iii 研究背景 1 材料與方法 7 結果 10 討論 13 參考文獻 19 圖表目錄 表一、病例組與對照組進入研究之基本特徵 24 表二、已知抗原決定位序列列表 25 表三、病例組與對照組中感染HBV基因型B型之基本特徵 29 表四、與急性發作相關之病毒抗原決定位胺基酸多型性之分佈 30 表五、Polymerase基因區與急性發作相關之病毒抗原決定位胺基酸多型性型態 31 表六、病毒抗原決定位之胺基酸多型性分佈與其他因子之關係 32 圖一、HBV全基因體之最大概似法親緣演化樹 34 圖二、單一個案病毒抗原決定位胺基酸序列隨時間變動之型態 35 圖三、病例組於不同時間點之抗原決定位變異比率 37 附表一、第二次聚合酶鏈鎖反應引子列表 38 附表二、序列反應引子列表 39 | |
dc.language.iso | zh-TW | |
dc.title | 免疫抗原決定位之胺基酸多型性與慢性 B 肝急性發作之關係:縱式研究 | zh_TW |
dc.title | Amino Acid Polymorphisms in Immune Epitope and Acute Exacerbation in Chronic Hepatitis B: Longitudinal Study | en |
dc.type | Thesis | |
dc.date.schoolyear | 100-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 劉信孚(Hsin-Fu Liu),鄭如茜(Ju-Chien Cheng),林志陵(Chih-Lin Lin) | |
dc.subject.keyword | B 型肝炎病毒,急性發作,免疫抗原決定位,胺基酸多型性, | zh_TW |
dc.subject.keyword | hepatitis B virus,acute exacerbation,immune epitope,amino acid polymorphisms, | en |
dc.relation.page | 39 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2012-07-23 | |
dc.contributor.author-college | 公共衛生學院 | zh_TW |
dc.contributor.author-dept | 流行病學與預防醫學研究所 | zh_TW |
顯示於系所單位: | 流行病學與預防醫學研究所 |
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