Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/22692
標題: 慢性C型肝炎病毒感染病患之第一型/第二型輔助T淋巴球活性變化及第十白血球間素啟動子基因單一核酸多形性與抗病毒藥物治療成效之相關
Association of Th1/Th2 Activity Changes and IL-10 Promoter Gene Polymorphism in Chronic HCV-Infected Patients and Responsiveness to Antiviral Treatment
作者: 楊勝舜
Yang, Sheng-Shun
關鍵字: Hepatitis C virus;C型肝炎病毒;interferon;ribavirin;sustained virologic response;host factor;Th1/Th2 lymphocytes;cytokines;IL-10 promoter gene;single nucleotide polymorphisms;干擾素;雷巴威林;持續病毒反應;宿主因素;第一型輔助T淋巴球;第二型輔助T淋巴球;細胞激素;第十白血球間素啟動子基因;單一核酸多型性
出版社: 生命科學系所
引用: 中文參考書目 中央健康保險局(2003).全民健康保險藥品給付規定.全民健康保險加強慢性C型肝炎治療試辦計畫公告,2003年9月26日健保審字第零九二零零二一三零九號。 中央健康保險局(2004).全民健康保險藥品給付規定.全民健康保險加強慢性C型肝炎治療試辦計畫公告,2004年8月1日健保審字第零九三零零六八五零三號。 許景盛、高嘉宏(2005).C型肝炎治療的新進展-干擾素相關治療的影響因素和因應策略.當代醫學,32(3),218-231。 梁程超、高嘉宏(2003).2002年C型肝炎治療共識簡介.當代醫學,30(4),314-319。 傅淑瑩(1999).慢性病毒性肝炎患者接受干擾素治療期間之疲倦感與自我照顧行為的探討.未發表的碩士論文,高雄:高雄醫學大學護理學研究所。 趙美珍(2004).肝硬化病患疲倦與睡眠品質之相關因素探討.未發表的碩士論文,臺北:臺北醫學大學護理學研究所。 劉俊人、賴明陽(1998).慢性C型肝炎之治療.台灣醫學,2(6),661-667。 賴明陽(2003).C型肝炎治療的最新進展.臨床醫學,51(2),96-100。 顏芳慧、許敏桃(2001).急性心肌梗塞婦女發病至求醫經驗.榮總護理,18(2),132-142。 鐘孟雄(2003).六週次運動訓練對B型肝炎學生肝功能及疲勞度之影響.未發表的碩士論文.臺北:台灣師範大學體育學研究所。 英文參考書目 Abayli B, Canataroglu A, Akkiz H. Serum profile of T helper 1 and T helper 2 cytokines in patients with chronic hepatitis C virus infection. Turk J Gastroenterol 2003; 14: 7-11. Abbott WGH, Rigopoulou E, Haigh P, et al. Single nucleotide polymorphisms in the interferon-γ and interleukin-10 genes do not influence chronic hepatitis C severity or T-cell reactivity to hepatitis C virus. Liver Intl 2004; 24: 90-7. Accapezzato D, Visco V, Francavilla V, et al. Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo. J Exp Med 2005; 202: 817-28. Agnello V, Abel G, Elfahal M, et al. Hepatitis C virus and other flaviviridae viruses enter cells via low density lipoprotein receptor. Proc Natl Acad Sci USA 1999; 96: 12766-71. Aizaki H, Saito S, Ogino T, et al. Suppression of interferon-induced antiviral activity in cells expressing hepatitis C virus proteins. J Interferon Cytokine Res 2000; 20: 1111-20. Alberti A, Noventa F, Benvegnu L, et al. Prevalence of asymptomatic persons with hepatitis C virus infection. Ann Intern Med 2002; 137: 961-4. Alexopoulou L, Holt AC, Medzhitov R, et al. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001; 413; 732-8. Alter HJ, Holland PV, Morrow AG, et al. Clinical and serological analysis of transfusion-associated hepatitis. Lancet 1975; 2: 838-41. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999; 341: 556-62. Andrejeva J, Childs KS, Young DF, et al. The V proteins of paramyxoviruses bind the IFN-inducible RNA helicase, MDA5, and inhibit its activation of the IFN-beta promoter. Proc Natl Acad Sci USA 2004; 101: 17264-9. Appay V, Dunbar PR, Callan M, et al. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med 2002; 8: 379-85. Appel N, Pietschmann T, Bartenschlager R. Mutational analysis of hepatitis C virus nonstructural protein 5A: potential role of differential phosphorylation in RNA replication and identification of a genetically flexible domain. J Virol 2005; 79: 3187-94. Aus dem Siepen M, Lohmann V, Wiese M, et al. Nonstructural 5A does not contribute to the resistance of hepatitis C virus replication to interferon alpha in cell culture. Virology 2005; 336: 131-6. Bacon BR. Treatment of patients with hepatitis C and normal serum aminotransferase levels. Hepatology 2002; 36: S179-84. Bain C, Fatmi A, Zoulim F, et al. Impaired allostimulatory function of dendritic cells in chronic hepatitis C infection. Gastroenterology 2001; 120: 512-24. Balasekaran R, Bulterys M, Jamal MM, et al. A case-control study of risk factors for sporadic hepatitis C virus infection in the southwestern United States. Am J Gastroenterol 1999; 94: 1341-6. Baron S, Tyring S K, Fleischmann W R, et al. The interferons. Mechanisms of action and clinical applications. JAMA 1991; 266: 1375-83. Barrera M, Sandler IN, Ramsay TB. Preliminary development of a scale of social support: Studies on college students. Am J Com Psy 1981; 9: 413-45. Bartenschlager R, Ahlborn-Laake L, Mous J, et al. Kinetic and structural analyses of hepatitis C virus polyprotein processing. J Virol 1994; 68: 5045-55. Barth H, Ulsenheimer A, Pape GR, et al. Uptake and presentation of hepatitis C virus-like particles by human dendritic cells. Blood 2005; 105: 3605-14. Bastardo YM, Kimberlin CL. Relationship between quality of life, social support and disease-related factors in HIV-infected persons in Venezuela. AIDS Care 2000; 12: 673-84. Bayliss MS, Gandek B, Bungay KM, et al. A questionnaire to assess the generic and disease-specific health outcomes of patients with chronic hepatitis C. Qual Life Res 2000; 7: 39-55. Beales LP, Holzenburg A, Rowlands DJ. Viral internal ribosome entry site structures segregate into two distinct morphologies. J Virol 2003; 77: 6574-9. Benhamou Y, Bochet M, Di Martino V, et al. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. The Multivirc Group. Hepatology 1999; 30: 1054-8. Beutler B. Inferences, questions and possibilities in Toll-like receptor signaling. Nature 2004; 430; 257-63. Bigger CB, Brasky KM, Lanford RE, et al. DNA microarray analysis of chimpanzee liver during acute resolving hepatitis C virus infection. J Virol 2001; 75: 7059-66. Birkel A, Caldwell L, Stafford-Fox V, et al. Combination interferon alfa-2b/Ribavirin therapy for the treatmen of hepatitis C: nursing implications. Gastroenterol Nursing 1999; 23: 55-62. Bissell DM. Sex and hepatic fibrosis. Hepatology 1999; 29: 988-9. Blight KJ, Kolykhalov AA, Rice CM. Efficient initiation of HCV RNA replication in cell culture. Science 2000; 290: 1972-4. Blindenbacher A, Duong FH, Hunziker L, et al. Expression of hepatitis C virus proteins inhibits interferon alpha signaling in the liver of transgenic mice. Gastroenterology 2003; 124: 1465-75. Bode JG, Ludwig S, Ehrhardt C, et al. IFN-alpha antagonistic activity of HCV core protein involves induction of suppressor of cytokine signaling-3. FASEB J 2003; 17: 488-90. Bonkovsky HL, Woolley JM, and the Consensus Interferon Study Group. Reduction of health-related quality in chronic hepatitis C and improvement with interferon therapy. Hepatology 1999; 29: 264-70. Bowen DG, Walker CM. Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature 2005a; 436: 946-52. Bowen DG, Walker CM. Mutational escape from CD8+ T cell immunity: HCV evolution, from chimpanzees to man. J Exp Med 2005b; 201: 1709-14. Bowie AG, Haga IR. The role of Toll-like receptors in the host response to viruses. Mol Immunol 2005; 42: 859-67. Breiman A, Grandvaux N, Kin R, et al. Inhibition of RIG-I-dependent signaling to the interferon pathway during hepatitis C virus expression and restoration of signaling by IKKepsilon. J Virol 2005; 79: 3969-78. Brillanti S, Levantesi F, Masi L, et al. Triple antiviral therapy as a new option for patients with interferon nonresponsive chronic hepatitis C. Hepatology 2000; 32: 630-4. Brooks DG, Trifilo MJ, Edelmann KH, et al. Interleukin-10 determines viral clearance or persistence in vivo. Nature Medicine 2006; 12: 1301-9. Brouwer JT, Hansen BE, Niesters HG, et al. Early prediction of response in interferon monotherapy and in interferon-ribavirin combination therapy for chronic hepatitis C: HCV RNA at 4 weeks versus ALT. J Hepatol 1999; 30: 192-8. Camps J, Castilla A, Ruiz J, et al. Randomised trial of lymphoblastoid alpha-interferon in chronic hepatitis C. Effects on inflammation, fibrogenesis and viremia. J Hepatol 1993; 17: 390-6. Carrere-Kremer S, Montpellier-Pala C, Cocquerel L, et al. Subcellular localization and topology of the p7 polypeptide of hepatitis C virus. J Virol 2002; 76: 3720-30. Cavalletto L, Chemello L, Donada C, et al. The pattern of response to interferon alpha (alpha-IFN) predicts sustained response to a 6-month alpha-IFN and ribavirin tretreatment for chronic hepatitis C. J Hepatol 2000; 33: 128-34. Chamberlain RW, Adams NJ, Taylor LA, et al. The complete coding sequence of hepatitis C virus genotype 5a, the predominant genotype in South Africa. Biochem Biophys Res Commun 1997; 236: 44-9. Chang KM, Rehermann B, McHutchison JG, et al. Immunological significance of cytotoxic T lymphocyte epitope variants in patients chronically infected by the hepatitis C virus. J Clini Invest 1997; 100: 2376-85. Chang MH, Lee CY, Chen DS. Minimal role of hepatitis C virus infection in childhood liver disease in an area hyperendemic for hepatitis B infection. J Med Virol 1993; 40: 322-25. Chayama K, Tsubota A, Kobayashi M, et al. Pretreatment virus load and multiple amino acid substitutions in the interferon sensitivity-determining region predict the outcome of interferon treatment in patients with chronic genotype 1b hepatitis C virus infection. Hepatology 1997; 25: 745-9. Chayama K, Suzuki F, Tsubota A, et al. Association of amino acid sequence in the PKR-eIF2 phosphorylation homology domain and response to interferon therapy. Hepatology 2000; 32: 1138-44. Chen CH, Yang PM, Huang GT, et al. Estimation of seroprevalence of hepatitis B virus and hepatitis C virus in Taiwan from a large-scale survey of free hepatitis screening participants. J Formos Med Assoc 2007; 106: 148-55. Chen DS, Kuo GC, Sung JL, et al. Hepatitis C virus infection in an area hyperendemic for hepatitis B and chronic liver disease: the Taiwan experience. J Infect Dis 1990; 162: 817-22. Chen DS, Wang JT, Chen PJ, et al. Hepatitis C virus infection in Taiwan. Gastroenterol Jpn 1991; 26: 164S-166S. Chen HM. Prescription adherence and its related factors in chronic hepatitis C patients receiving regimen of interferon and ribavirin treatment- A longitudinal study. Unpublished master’s thesis, National Taiwan University, Taipei, Taiwan, 2006. Chen M, Sallberg M, Sonnerborg A, et al. Limited humoral immunity in hepatitis C virus infection. Gastroenterology 1999; 116: 135-43. Choo QL, Kuo G, Weiner AJ. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989; 244: 359-62. Choo QL, Richman KH, Han JH, et al. Genetic organization and diversity of the hepatitis C virus. Proc Natl Acad Sci USA 1991; 88: 2451-5. Chu MW, Ostertag D, Li ZW, et al. JNK2 and IKKbeta are required for activating the innate response to viral infection. Immunity 1999; 11: 721-31. Chung KM, Song OK, Jang SK. Hepatitis C virus nonstructural protein 5A contains potential transcriptional activator domains. Mol Cell Biol 1997; 7: 661-7. Chung RT, Monto A, Dienstag J L, et al. Mutations in the NS5A region do not predict interferon-responsiveness in American patients infected with genotype 1b hepatitis C virus. J Med Virol 1999; 58: 353-8. Colonna M, Krug A, Cella M. Interferon-producing cells: on the front line in immune responses against pathogens. Curr Opin Immunol 2002: 14: 373-9. Comandini UV, Tossini G, Longo MA, et al. Sporadic hepatitis C virus infection: a case-control study of transmission routes in a selected hospital sample of the general population in Italy. Scand J Infect Dis 1998; 30: 11-5. Constantini PK, Wawrzynowicz-Syczewska M, Clare M, et al. Interleukin-1, interleukin-10 and tumor necrosis factor-alpha gene polymorphisms in hepatitis C virus infection: an investigation of the relationships with spontaneous viral clearance and response to alpha-interferon therapy. Liver 2002; 22: 404-12. Cooper S, Erickson AL, Adams EJ, et al. Analysis of a successful immune response against hepatitis C virus. Immunity 1999; 10: 439-49. Cox AL, Mosbruger T, Mao Q, et al. Cellular immune selection with hepatitis C virus persistence in humans. J Exp Med 2005; 201: 1741-52. Crotta S, Stilla A, Wack A, et al. Inhibition of natural killer cells through engagement of CD81 by the major hepatitis C virus envelope protein. J Exp Med 2002; 195: 35-41. Dai CY, Chuang WL, Chang WY, et al. Tumor necrosis factor- alpha promoter polymorphism at position -308 predicts response to combination therapy in hepatitis C virus infection. J Infect Dis 2006; 193: 98-101. Dalgard O, Bjoro K, Hellum K, et al. Treatment with pegylated interferon and ribavirin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology 2005; 40: 1260-65. Dal Molin G, D''Agaro P, Ansaldi F, et al. Mother-to-infant transmission of hepatitis C virus: rate of infection and assessment of viral load and IgM anti-HCV as risk factors. J Med Virol 2002; 67: 137-42. David M, Petricoin E 3rd, Benjamin C, et al. Requirement for MAP kinase (ERK2) activity in interferon alpha- and interferon beta-stimulated gene expression through STAT proteins. Science 1995; 269: 1721-3. Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa: a multicenter randomized, controlled trial. N Engl J Med 1989; 321: 1501-6. Davis GL, Esteban-Mur R, Rustgi V, et al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. N Engl J Med 1998; 339: 1493-9. Davis G L. New schedules of interferon for chronic hepatitis C. J Hepatol 1999; 31: 227S-31S. Davis GL, Wong JB, McHutchison JG, et al. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003; 38: 645-52. De Francesco R, Steinkühler C. Structure and function of the hepatitis C virus NS3-NS4A serine protease. Curr Top Microbiol Immunol 2000; 242: 149-69. de Lucas S, Bartolome J, Carreno V. Hepatitis C virus core protein down-regulates transcription of interferon-induced antiviral genes. J Infect Dis 2005; 191: 93-9. Del Prete G, De Carli M, Almerigogna F, et al. Preferential expression of CD30 by human CD4 T cells producing Th2-type cytokines. FASEB J 1995; 9: 81-6. De Moliner L, Pontisson P, De Salvo GL, et al. Serum and liver HCV RNA levels in patients with chronic hepatitis C: Correlation with clinical and histological features. Gut 1998; 42: 856-60. Der SD, Zhou A, Williams BR, Silverman RH. Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci USA 1998; 95: 15623-8. de Veer MJ, Holko M, Frevel M, et al. Functional classification of interferon-stimulated genes identified using microarrays. J Leukoc Biol 2001; 69: 912-20. Di Bisceglie AM, Martin P, Kassianides C, et al. Recombinant interferon alfa therapy for chronic hepatitis C: a randomized, double-blind, placebo-controlled trial. N Engl J Med 1989: 321: 1506-10. Diebold SS, Montoya M, Unger H, et al. Viral infection switches non-plasmacytoid dendritic cells into high interferon producers. Nature 2003; 424: 324-8. Diepolder HM, Zachoval R, Hoffmann RM, et al. Possible mechanism involving T-lymphocyte response to non-structural protein 3 in viral clearance in acute hepatitis C virus infection. Lancet 1995; 346: 1006-7. Dore GJ, Law M, MacDonald M, et al. Epidemiology of hepatitis C virus infection in Australia. J Clin Virol 2003; 26: 171-84. Dubisson J, Helle F, Cocquerel L. Early steps of the hepatitis C virus life cycle. Cell Microbiol 2008; 10: 821-7. Duong FH, Filipowicz M, Tripodi M, et al. Hepatitis C virus inhibits interferon signaling through up-regulation of protein phosphatase 2A. Gastroenterology 2004; 126: 263-77. Dupuis S, Jouanguy E, Al-Hajjar S, et al. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet 2003; 33: 388-91. Duverlie G, Khorsi H, Castelain S, et al. Sequence analysis of NS5A protein of European hepatitis C virus 1b isolates and relation to interferon sensitivity. J Gen Virol 1998; 79: 1373-81. Eckart MR, Selby M, Masiarz F, et al. The hepatitis C virus encodes a serine protease involved in processing of the putative nonstructural proteins from the viral polyprotein precursor. Biochem Biophys Res Commun 1993; 192: 399-406. Edwards-Smith CJ, Jonsson JR, Purdie DM, et al. Interleukin-10 promoter polymorphism predicts initial response of chronic hepatitis C to interferon alfa. Hepatology 1999; 30: 526-30. El-Serag HB, Hampel H, Yeh C, et al. Extrahepatic manifestations of hepatitis C among United States male veterans. Hepatology 2002; 36: 1439-45. El-Shamy A, Nagano-Fujii M, Sasase N, et al. Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy. Hepatology 2008; 48: 1-10. Enomoto N, Sakuma I, Asahina Y, et al. Comparison of full-length sequences of interferon-sensitive and resistant hepatitis C virus 1b. J Clin Investig 1995; 96: 224-30. Enomoto N, Sakuma I, Asahina Y, et al. Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med 1996; 334: 77-81. Erickson AL, Kimura Y, Igarashi S, et al. The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity 2001; 15: 885-95. Eskdale J, Gallagher G, Verweij CL, et al. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Pros Natl Acad Sci USA 1998; 95: 9465-70. Eskdale J, Keijsers V, Huizinga TWJ, et al. Microsatellite alleles and single nucleotide polymorphisms (SNP) combine to form four major haplotype families at the human interleukin-10 (IL-10) locus. Genes and Immunity 1999; 1: 151-5. Eyster ME, Alter HJ, Aledort LM, et al. Heterosexual co-transmission of hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Ann Intern Med 1991; 115: 764-8. Fang SH, Lai MY, Hwang LH, et al. Ribavirin enhances interferon-gamma levels in patients with chronic hepatitis C treated with interferon-alpha. J Biomed Sci 2001; 8: 484-91. Farci P, Alter HJ, Govindarajan S, et al. Lack of protective immunity against reinfection with hepatitis C virus. Science 1992; 258: 135-40. Farci P, Shimoda A, Coiana A, et al. The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science 2000; 288: 339-44. Ferrero S, Lungaro P, Bruzzone BM, et al. Prospective study of mother-to-infant transmission of hepatitis C virus: a 10-year survey (1990-2000). Acta Obstet Gynecol Scand 2003; 82: 229-34. Fitzgerald KA, McWhirter SM, Faia KL, et al. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat Immunol 2003; 4: 491-6. Foschi FG, Gramenzi A, Castelli E, et al. Soluble CD30 serum level in HCV-positive chronic active hepatitis: a surrogate marker of disease activity? Cytokine 2000; 12: 815-8. Foster GR, Goldin RD, Thomas HC. Chronic hepatitis C virus infection causes a significant reduction in quality of life in the absence of cirrhosis. Hepatology 1998; 27: 209-12. Foster GR. Hepatitis C virus infection: quality of life and side effects of treatment. J Hepatol 1999; 31: 250-4. Foy E, Li K, Wang C, et al. Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 2003; 300: 1145-8. François C, Duverlie G, Rebouillat D, et al. Expression of hepatitis C virus proteins interferes with the antiviral action of interferon independently of PKR-mediated control of protein synthesis. J Virol 2000; 74: 5587-96. Frasca L, Del Porto P, Tuosto L, et al. Hypervariable region 1 variants act as TCR antagonists for hepatitis C virus-specific CD4+ T cells. J Immunol 1999; 163: 650-8. Frese M, Pietschmann T, Moradpour D, et al. Interferon-alpha inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway. J Gen Virol 2001; 82: 723-33. Frese M, Schwarzle V, Barth K, et al. Interferon-gamma inhibits replication of subgenomic and genomic hepatitis C virus RNAs. Hepatology 2002; 35: 694-703. Friedland J, Renwick R, McColl M. Coping and social support as determinants of quality of life in HIV/AIDS. AIDS Care 1996; 8: 1520-6. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. New Engl J Med 2002, 347: 975-82. Fukuma T, Enomoto N, Marumo F, et al. Mutations in the interferon-sensitivity determining region of hepatitis C virus and transcriptional activity of the nonstructural region 5A protein. Hepatology 1998; 28: 1147-53. Gale M and Foy EM. Evasion of intracellular host defense by hepatitis C virus. Nature 2005; 436: 939-45. Gale M, Katze MG. Molecular mechanisms of interferon resistance mediated by viral-directed inhibition of PKR, the interferon-induced protein kinase. Pharmacol Ther 1996; 78: 29-46. Gale M, Korth MJ, Tang SL, et al. Evidence that hepatitis C virus resistance to interferon is mediated through the repression of the PKR protein kinase by the non-structural 5A protein. Virology 1997; 230: 217-27. Gale M, Blakely CM, Kwieciszewski B, et al. Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: Molecular mechanisms of kinase regulation. Mol Cell Biol 1998; 18: 5208-18. Garson JA, Brillanti S, Whitby K, et al. Analysis of clinical and virological factors associated with response to alpha interferon therapy in chronic hepatitis C. J Med Virol 1995; 45: 348-53. Gerlach JT, Diepolder HM, Jung MC, et al. Recurrence of hepatitis C virus after loss of virus-specific CD4(+) T-cell response in acute hepatitis C. Gastroenterology 1999; 117: 933-41. Gerlach JT, Ulsenheimer A, Gruner NH, et al. Minimal T-cell-stimulatory sequences and spectrum of HLA restriction of immunodominant CD4+ T-cell epitopes within hepatitis C virus NS3 and NS4 proteins. J Virol 2005; 79: 12425-33. Ghany MG, Kleiner DE, Alter H, et al. Progression of fibrosis in chronic hepatitis C. Gastroenterology 2003; 124: 97-104. Ghosh AK, Majumder M, Steele R, et al. Hepatitis C virus NS5A protein modulates transcription through a novel cellular transcription factor SRCAP. J Biol Chem 2000; 275: 7184-8. Gifford SM, O’Brien ML, Bammer G, et al. Australian women’s experiences of living with hepatitis C virus: Results from a cross-sectional survey. J Gastroenterol Hepatol 2003; 18: 841-50. Giorgi A. Phenomenology and psychological research. Pittsburgh, PA: Duquesnw University Press. 1988. Glacken M, Coates V, Kernohan G, et al. The experience of fatigue for people living with hepatitis C. J Clin Nursing 2003; 129: 244-53. Gonzalez-Peralta RP, Davis GL, Lau JY. Pathogenetic mechanisms of hepatocellular damage in chronic hepatitis C virus infection. J Hepatol 1994; 21: 255-9. Grakoui A, Wychowski C, Lin C, et al. Expression and identification of hepatitis C virus polyprotein cleavage products. J Virol 1993; 67: 1385-95. Grakoui A, Shoukry NH, Woollard DJ, et al. HCV persistence and immune evasion in the absence of memory T cell help. Science 2003; 302: 659-62. Gruener NH, Gerlach TJ, Jung MC, et al. Association of hepatitis C virus-specific CD8+ T cells with viral clearance in acute hepatitis C. J Infect Dis 2000; 181: 1528-36. Guidotti LG, Chisari FV. Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol 2001; 19: 65-91. Gumber SC, Chopra SC. Hepatitis C: A multifaced disease. Review to extrahepatic manifestations. Ann Intern Med 1995; 123: 615-20. Guo JT, Bichko VV, Seeger C. Effect of alpha interferon on the hepatitis C virus replicon. J Virol 2001; 75: 8516-23. Guo JT, Sohn JA, Zhu Q, Seeger C. Mechanism of the interferon alpha response against hepatitis C virus replicons. Virology 2004; 325: 71-81. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon alfa-2a and ribavirin combination therapy in chronic hepatitis C: randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004; 140: 346-55. Han J, Shyamala K, Richman B, et al. Characterization of terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5’ untranslated region and poly(A) tails at the 3’ end. Proc Natl Acad Sci USA 1991; 88: 1711-5. Han JQ and Batron DJ. Activation and evasion of the antiviral 2’-5’ oligoadenylate synthetase/ribonuclease L pathway by hepatitis C virus mRNA. RNA 2002; 8: 512-25. Hassanein T, Cooksley G, Sulkowski M, et al. The impact of peginterferon alfa-2a plus ribavirin combination therapy on health-related quality of life in chronic hepatitis C. J Hepatol 2004; 40: 675-81. Hegen M, Niedobitek G, Klein CE, et al. The triggering molecule Tp103 is associated with dipeptidyl aminopeptidase IV activity. J Immunol 1990; 144: 2908-14. Heim MH, Moradpour D, Blum HE. Expression of hepatitis C virus proteins inhibits signal transduction through the Jak-STAT pathway. J Virol 1999; 73: 8469-75. Heitkemper M, Jarrett M, Kurashige EM, et al. Chronic hepatitis C implications for health-related quality of life. Gastroenterol Nursing 2000; 24: 170-7. Hernandez ME, Bruguera M, Puyuelo T, et al. Risk of needle-stick injuries in the transmission of hepatitis C virus in hospital personnel. J Hepatol 1992; 16: 56-8. Hino K, Sainokami S, Shimoda K, et al. Genotypes and titers of hepatitis C virus for predicting response to interferon in patients with chronic hepatitis C. J Med Virol 1994; 42: 299-305. Hiscott J, Pitha P, Genin P, et al. Triggering the interferon response: the role of IRF-3 transcription factor. J Interferon Cytokine Res 1999; 19: 1-13. Hong X, Yu RB, Sun NX, et al. Human leukocyte antigen class II DQB1*0301, DRB1*1101 alleles and spontaneous clearance of hepatitis C virus infection: a meta-analysis. World J Gastroenterol 2005; 11: 7302-7. Hoofnagle JH, Mullen KD, Jones DB, et al. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon: a preliminary report. N Engl J Med 1986; 315: 1575-8. Hoofnagle JH. Therapy of acute and chronic viral hepatitis. Adv Intern Med 1994; 39: 241-75. Hoofnagle JH. Course and outcome of hepatitis C. Hepatology 2002; 36 (5 Suppl 1): S21-9. Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med 2006; 355: 2444-51. Hopwood M, Treloar C. The experience of interferon-based treatments for heaptitis C infection. Qualitative Health Res 2005; 15: 635-46. Hoshimoto K, Ohta N, Ohkura T, Inaba N. Changes in plasma soluble CD26 and CD30 during pregnancy: markers of Th1/Th2 balance? Gynecol Obstet Invest 2000: 50: 260-3. Hovanessian A G. Interferon-induced and double-stranded RNA-activated enzymes: a specific protein kinase and 2’,5’-oligoadenylate synthetases. J Interferon Res 1991; 11: 199-205. Huang CS, Ho MS, Yang CS, et al. Hepatitis C markers in hemodialysis patients. J Clin Microbiol 1993; 31: 1764-9. Hui DJ, Bhasker CR, Merrick WC, et al. Viral stress-inducible protein p56 inhibits translation by blocking the interaction of eIF3 with the ternary complex eIF2.GTP.Met-tRNAi. J Biol Chem 2003; 278: 39477-82. Hung CH, Lee CM, Lu SN, et al. Mutations in the NS5A and E2-PePHD region of hepatitis C virus type 1b and correlation with the response to combination therapy with interferon and ribavirin. J Viral Hepat 2003; 10: 87-94. Hussy P, Langen H, Mous J, et al. Hepatitis C virus core protein: carboxy-terminal boundaries of two processed species suggest cleavage by a signal peptide peptidase. Virology 1996; 224: 93-104. Iwasaki A and Medzhitov R. Toll-like receptor control of the adaptive immune response. Nat Immunol 2004; 5: 375-88. Jessop AB, Cohen C, Burke MM, et al. Hepatitis support group: meeting the information and support needs of hepatitis patients. Gastroenterol Nursing 2004; 27: 163-9. Jinushi M, Takehara T, Tatsumi T, et al. Negative regulation of NK cell activities by inhibitory receptor CD94/NKG2A leads to altered NK cell-induced modulation of dendritic cell functions in chronic hepatitis C virus infection. J Immunol 2004; 173: 6072-81. Kahn DL. Ways of discussing validity in qualitative nursing research. West J Nursing Res 1993; 15:122-5. Kang SC, Hwang SJ, Lee SH, et al. Health-related quality of life and impact of antiviral treatment in Chinese patients with chronic hepatitis C in Taiwan. World J Gastroenterol 2005; 1: 7494-8. Kao JH, Chen PJ, Lai MY, et al: Genotypes of hepatitis C virus in Taiwan and the progression of liver disease. J Clin Gastroenterol 1995; 21: 233-7. Kao JH, Chen PJ, Lai MY, et al. Positive and negative strand of hepatitis C virus RNA sequences in peripheral blood mononuclear cells in patients with chronic hepatitis C: no correlation with viral genotype 1b, 2a, and 2b. J Med Virol 1997; 52: 270-4. Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis 2002; 2: 395-403. Katayama K, Kasahara A, Sasaki Y, et al. Immunological response to interferon-gamma priming prior to interferon-alpha treatment in refractory chronic hepatitis C in relation to viral clearance. J Virol Hepat 2001; 8: 180-5. Kato H, Sato S, Yoneyama M, et al. Cell type-specific involvement of RIG-I in antiviral response. Immunity 2005; 23: 19-28. Kato N, Hijikata M, Ootsuyama Y, et al. Molecular cloning of the human hepatitis C virus genome from Japanese patients with non-A, non-B hepatitis. Proc Natl Acad Sci USA 1990; 87: 9524–8. Kato N, Lan KH, Ono-Nita SK, et al. Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator. J Virol 1997; 71: 8856-9. Kato N, Lan KH, Ono-Nita SK, et al. Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator. In: Schinazi RF, Sommadossi JP, Thomas HC, eds. Therapies for Viral Hepatitis. London: International Medical Press, 1998: 255-62. Keane NM, Price P, Lee S, et al. An evaluation of serum soluble CD30 levels and serum CD26 (DPPIV) enzyme activity as markers of type 2 and type 1 cytokines in HIV patients receiving highly active antiretroviral therapy. Clin Exp Immunol 2001; 126: 111-6. Kerkmann M, Rothenfusser S, Hornung V, et al. Activation with CpG-A and CpG-B oligonucleotides reveals two distinct regulatory pathways of type I IFN synthesis in human plasmatocytoid dendritic cells. J Immunol 2003; 170: 4465-74. Khakoo SI, Thio CL, Martin MP, et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 2004; 305: 872-4. Khorsi H, Castelain S, Wyseur A, et al. Mutations of hepatitis C virus 1b NS5A 2209-2248 amino acid sequence do not predict the response to recombinant interferon-alfa therapy in French patients. J Hepatol 1997; 27: 72-7. Kiyosawa K, Sodeyama T, Tanaka E, et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis of detection of antibody to hepatitis C virus. Hepatology 1990; 12: 671-5. Kleinman L, Zodet MW, Hakim Z, et al. Psychometric evaluation of the fatigue severity scale for use in chronic hepatitis C. Qual Life Res 2000; 9: 499-508. Klenerman P, Zinkernagel RM. Original antigenic sin impaires cytotoxic T lymphocyte response to viruses bearing variant epitopes. Nature 1998; 394: 482-5. Kolykhalov AA, Mihalik K, Feinstone SM, et al. Hepatitis C virus-encoded enzymatic activities and conserved RNA elements in the 3’ nontranslated region are essential for virus replication in vivo. J Virol 2001; 74: 2046-51. Ko YC, Ho MS, Chiang TA, et al. Tattooing as a risk of hepatitis C virus infection. J Med Virol 1992; 38: 288-91. Kubo M, Hanada T, Yoshimura A. Suppressors of cytokine signaling and immunity. Nat Immunol 2003; 4: 1169-76. Kumar U, Monjardino J, Thomas HC. Hypervariable region of hepatitis C virus envelope glycoprotein (E2/NS1) in an agammaglobulinemic patient. Gastroenterology 1994; 106: 1072-5. Kuo G, Choo QL, Alter HJ, et al. An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 1989; 244: 362-4. Kwok S, Higuchi R. Avoiding false positives with PCR. Nature 1989; 339: 237-8. Lagging LM, Meyer K, Hoft D, et al. Immune responses to plasmid DNA encoding the hepatitis C virus core protein. J Virol 1995; 69: 5859-63. Lai ME, Mazzoleni AP, Argiolu F, et al. Hepatitis C virus in multiple episodes of acute hepatitis in polytransfused thalassaemic children. Lancet 1994; 343: 388-90. Lai MY, Kao JH, Yang PM, et al. Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Gastroenterology 1996; 111: 1307-12. Lanier LL. Activating and inhibitory NK cell receptors. Adv Exp Med Biol 1998; 452: 13-8. Latifa T F Yeung, Susan M King, et al. Mother-to-infant transmission of hepatitis C virus. Hepatology 2001; 34: 223-9. Lau JY, Tam RC, Liang TJ, et al. Mechanism of action of ribavirin in the combination treatment of chronic HCV infection. Hepatology 2002; 35: 1002-9. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med 2001; 345: 41-52. Lauer GM, Barnes E, Lucas M, et al. High resolution analysis of cellular immune responses in resolved and persistent hepatitis C virus infection. Gastroenterology 2004; 127: 924-36. Lechner F, Gruener NH, Urbani S, et al. CD8+ T lymphocyte responses in resolved and persistent hepatitis C virus infection. Eur J Immunol 2000a; 30: 2479-87. Lechner
摘要: 
C型肝炎病毒感染引起急性和慢性肝炎、肝硬化、肝癌以及肝外表現等相當多的肝病。至今為止,C型肝炎感染之致病機轉大部份不明朗,猜測可能的原因為病毒和宿主免疫反應之交互作用以及病毒逃避宿主攻擊的能力。同時,導致C型肝炎病毒不同臨床結局以及對抗病毒藥物治療反應之病毒和宿主因素尚未明朗,一般相信特定之免疫調控細胞,例如不同的T淋巴球之間的不平衡在C型肝炎病毒持續感染的致病上應該扮演一個重要的角色。根據過去的研究,人類T淋巴球因應不同微生物的侵犯有兩種型式的功能,首先是第一型輔助T淋巴球,傾向於在感染到細胞內病原時製造出來,可以誘發細胞性免疫反應;其次為第二型輔助T淋巴球,通常是攻擊細胞外之病原或微生物例如蠕虫感染或是過敏原,可以引發體液性或抗體調控性之免疫反應。在某些感染症、過敏和免疫疾病都有細胞激素調控的免疫失調或是所謂的 「第一型輔助T淋巴球/第二型輔助T淋巴球失衡」的情形。第一型輔助T淋巴球和第二型輔助T淋巴球不僅有不同的功能特性,它們也具有不同的表面指標。干擾素合併雷巴威林是當前治療慢性C型肝炎的標準療法,可以有大約40-60%之持續病毒反應,但是仍然有相當高的失敗病例。僅管干擾素有抗病毒及免疫調節的雙重功效,慢性C型肝炎病患血清中第一型輔助T淋巴球/第二型輔助T淋巴球的活性及其與治療反應之相關至今不明。本研究乃在探討慢性C型肝炎病患接受24週干擾素合併雷巴威林治療之第一型輔助T淋巴球/第二型輔助T淋巴球活性的變化,利用定量檢測治療前及停藥後六個月病患血清可溶性CD26及CD30(分別是第一型輔助T淋巴球和第二型輔助T淋巴球的表面指標),評估其濃度改變和治療反應之間的相關性。慢性C型肝炎病患依干擾素合併雷巴威林治療效果區分成兩組,33位當中有15位(45%)達到持續性病毒反應。兩組之間的基因型分佈相似。相較於無持續病毒反應組,達成持續病毒反應者年齡較輕,而且治療前C型肝炎病毒量較低、ALT值較高。依線性迴歸分析,治療前ALT值和治療前可溶性CD26及可溶性CD30值並無顯著相關。和健康成人相較,慢性C型肝炎病患不論有否達成持續病毒反應,在合併治療前後可溶性CD26值均顯著偏低(治療前140.4 ± 63.9 ng/mL vs 200.6 ± 60.3 ng/mL,P < 0.0001;治療後115.9 ± 32.9 ng/mL vs 200.6 ± 60.3 ng/mL,P < 0.0001)。此外慢性C型肝炎未達成持續性病毒反應者較達成持續性病毒反應者可溶性CD26值顯著偏低(139.0 ± 50.9 ng/mL vs 117.7 ± 40.3 ng/mL,P = 0.039)。反之慢性C型肝炎病患之治療前可溶性CD30值顯著地高於治療後,而且這個值在慢性C型肝炎達成持續性病毒反應者於治療後六個月低於未達成持續性病毒反應者(6.4 ± 3.5 U/mL vs 10.4 ± 5.4 U/mL,P = 0.021),至於這兩組病患和健康成人對照組在治療前後均無統計差異;而達成持續性病毒反應者治療前CD30高於健康對照組,治療後CD30則相當低。此研究顯示慢性C型肝炎病患體內之第一型輔助T淋巴球活性較健康成人者低,而此活性在未達成持續性病毒反應者較達成持續性病毒反應者更低,代表慢性C型肝炎病患的免疫能力缺失,而且第一型輔助T淋巴球活性愈低者治療反應愈差;此外有顯著的治療前後第二型輔助T淋巴球活性下降者通常較容易治療成功。
除了前述抗病毒藥物療效有其限制之外,此種治療價格昂貴、副作用多也使得尋找一個最佳療效的預測指標一直是學者們努力研究的方向,「基因型」以及能達到「快速或早期病毒反應」是目前已知比較重要的指標。過去研究指出宿主的細胞激素濃度差異可以解釋C型肝炎病毒感染的不同臨床結果,比方第十白血球間素(interleukin-10,IL-10)是一個相當強的第二型輔助T淋巴球抗發炎細胞激素,主要由單核細胞、巨噬細胞和T細胞製造,它可以調降主要組織相容性複合體class I和class II分子,同時製造第一型輔助T淋巴球之細胞激素。人類第十白血球間素基因位於第一對染色體,可以編碼5個外顯子(大小為5.1 kb)。第十白血球間素的濃度在不同個體之間差異很大,極可能源自第十白血球間素啟動子基因涵蓋兩個訊息性微衛星IL-10 G和IL-10 R區域之單一核酸多型性(分別是位於轉錄起始點上游1,2和4 kb之處),當中最常見之單點突變位於轉錄起始點上游-1082(G/A),-81 (C/T),及-592(C/A)。目前已知-1082(G),-819(C),及-592(C) 對偶基因經常合併比較高的第十白血球間素製造量(可能包含單核細胞和T細胞)。最近有西方國家研究指出第十白血球間素啟動子基因之ATA 單倍體型(haplotype)和受感染宿主是否能自發地清除C型肝炎病毒相關。這種觀察是否適用於亞洲慢性C型肝炎病患身上尚有待證實。我們分析台灣慢性C型肝炎接受長效型干擾素合併雷巴威林治療之病患血中第十白血球間素啟動子基因之單一核酸多型性,並與健康成人進行比較。143位慢性C型肝炎病患,97位(67.8%)達到持續病毒反應,在第十白血球間素啟動子基因轉錄起始點上游-1082,-819及-592位置之單一核酸多型性在慢性C型肝炎病患和健康對照組(共134位)之間以及持續病毒反應和未達成持續病毒反應兩組間均未有統計差異。血中第十白血球間素濃度在慢性C型肝炎病患和健康對照組之間以及持續病毒反應和未達成持續病毒反應兩組間均未有統計差異。慢性C型肝炎病患之ATA單倍體型頻率為70.3%,在健康對照組則為69.8%(白種人慢性C型肝炎ATA單倍體型佔23.0%、健康對照組為24.8%);此外ATA單倍體型頻率在慢性C型肝炎持續病毒反應和未達到持續病毒反應兩組間亦無統計上之差異。此一研究顯示第十白血球間素啟動子基因之單一核酸多型性在台灣慢性C型肝炎病患治療成效上並非主要的影響因素,第十白血球間素啟動子基因ATA單倍體型在不同種族之間的差異是否為影響其治療反應之重要因素有待進一步釐清。

Hepatitis C virus (HCV) infection causes a wide spectrum of liver disease ranging from acute and chronic hepatitis, liver cirrhosis, hepatocellular carcinoma and several extrahepatic manifestations. The viral and host factors responsible for clinical outcomes of HCV infection have not yet been clarified. Clearance of hepatitis C virus is attributed to host cellular immune responses, in which T helper cells play a critical role. We studied the serial changes of serum soluble markers released from T helper 1 (Th1) and 2 (Th2) and their correlations with treatment responses in chronic hepatitis C patients receiving interferon-α plus ribavirin for 24 weeks. Serum markers (soluble CD26 and CD30 levels) of T helper cells were quantified before and 6 months after combination therapy in 33 chronic hepatitis C patients and in 20 healthy controls. Our results showed that younger age and higher pretreatment ALT levels were associated with higher sustained virologic response (SVR). Compared to healthy controls, chronic hepatitis C patients had significantly lower serum soluble CD26 levels before (140.4 ± 63.9 ng/mL vs 200.6 ± 60.3 ng/mL, p < 0.0001) and after (115.9 ± 32.9 ng/mL vs 200.6 ± 60.3 ng/mL, p < 0.0001) combination therapy. The level was even lower in those with non-SVR (139.0 ± 50.9 ng/mL vs 117.7 ± 40.3 ng/mL, p = 0.039). In contrast, soluble CD30 levels at 6 months after combination therapy were significantly lower in patients with SVR than those with non-SVR (6.4 ± 3.5 U/mL vs 10.4 ± 5.4 U/mL, p = 0.021). In conclusion, chronic hepatitis C patients have a weak Th1 response as reflected by lower soluble CD26 levels and the levels are even lower in non-sustained responders. In sharp contrast, down regulation of Th2 response with serial changes of soluble CD30 level is associated with successful treatment of HCV infection.
In the meantime, host genetic factors may affect clinical outcomes of hepatitis C virus infection; however, the possible mechanisms remain largely unknown. The role of immunopathogenesis in chronic hepatitis C leads to extensive exploration on host immunity including inflammatory cytokines. We thus examined IL-10 promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site and studied their association with response to 24 weeks of pegylated interferon plus ribavirin treatment in 143 chronic hepatitis C patients, of whom 97 (67.8%) achieved a sustained virologic response (SVR). In addition, 134 healthy adults were used as controls. Of chronic hepatitis C patients, 111 (77.6%) were genotype 1 infection, 32 (22.4%) were genotype 2 infection. Patients with sustained virologic response (SVR) were younger and had higher pretreatment ALT level than those without. No statistical difference was found between chronic hepatitis C patients who achieved SVR or not in terms of gender, HCV genotype, pretreatment HCV RNA level, and severity of liver disease. The serum IL-10 levels were comparable between healthy controls and chronic hepatitis C patients as well as between HCV patients with and without SVR. The distribution of IL-10 promoter gene polymorphisms at positions -1082, -819, and -592 relative to transcription start site was comparable between HCV patients and healthy controls as well as HCV patients with and without SVR. In contrast to a study from western country, a high frequency of ATA haplotype of common IL-10 promoter gene SNPs was found in both chronic hepatitis C patients (70.3%) and healthy controls (68.9%) (23.0% in Caucasian chronic hepatitis C patients and 24.8% in healthy controls). However, ATA haplotype was not associated with SVR in chronic hepatitis C patients. In conclusion, our data fail to demonstrate the influence of IL-10 promoter gene polymorphisms on the response to combination therapy in Taiwanese chronic hepatitis C patients. The impact of genetic variations in IL-10 haplotype on the response to anti-HCV treatment among different ethnic populations deserves further examination.
URI: http://hdl.handle.net/11455/22692
其他識別: U0005-1711200816052400
Appears in Collections:生命科學系所

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