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研究生:黄奕文
研究生(外文):Yi-Wen Huang
論文名稱:慢性B型肝炎患者免疫遺傳、免疫受體與免疫調節之研究
論文名稱(外文):Studies on Immunogenetics, Immune-Receptors, and Immunomodulation in Chronic Hepatitis B Patients
指導教授:高嘉宏高嘉宏引用關係
指導教授(外文):Jia-Horng Kao
口試委員:簡榮南劉俊人林俊彥
口試委員(外文):Rong-Nan ChienChun-Jen LiuChun-Yen Lin
口試日期:2013-05-28
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:臨床醫學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:145
中文關鍵詞:B 型肝炎免疫的人類白血球抗原維生素D受體類鐸受體3核醣核酸干擾素
外文關鍵詞:hepatitis Bimmunehuman leukocyte antigenvitamin D receptortoll-like receptor-3ribonucleic acidinterferon
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目前仍然未知那些宿主免疫遺傳及免疫受體因素影響慢性B型肝炎急性發作的嚴重度。我們的目的在於探討免疫遺傳因子HLA-DRB1多形性與男性慢性B型肝炎之肝炎嚴重程度之間的相關性。在此前瞻性世代研究中,共納入了204名在門診已追蹤一年以上的B肝帶原者 (131名男性和73名女性)。50名ALT < 2X正常值上限 (第一組、平均追蹤83.6個月) 與154名ALT ≧ 2X正常值上限 (第二組、平均跟蹤81.3個月)的帶原者進行比較。HLA-DRB1的對偶基因採用聚合酶鏈反應-序列特定寡核苷酸探針雜交法,而病毒基因型以熔解曲線分析鑒定。在男性帶原者中發現第一組之18% 和第二組之8%帶有HLA-DRB1*1101(調整年齡後OR 0.23, p = 0.020),女性帶原者是4% 相較於 9.4%(p = 0.094)。男性攜帶DRB1*1101者,其B肝病毒基因型的分佈在兩組之間是相似的。HLA-DRB1*1101與臺灣男性慢性B肝帶原者的輕度肝炎有關。
對於慢性感染和癌症,維生素D可通過維生素D受體 (VDR) 發揮免疫調節和抗增殖作用。我們訂定分為6個不同組別的250名臺灣慢性B肝帶原者之三個多形性限制位點的基因型 (BsmI (rs1544410)、ApaI (rs7975232) 及TaqI (rs731236))。調整年齡和性別後,肝炎急性發作患者的維生素D受體B/b、B/a、B/T、B/a/T頻率均低於未發生急性發作者 (7% 相較於20%,p=0.009;1% 相較於9%,p=0.004;3% 相較於10%,p=0.007;1% 相較於9%,p=0.005);相反的,肝炎急性發作患者的T/t、A/T、A/t、b/A/t頻率分佈均較高 (8% 相較於3%,p=0.003;49% 相較於34%,p=0.027;2% 相較於1%,P=0.004;0.5% 相較於0%,p=0.001)。此外,HBeAg陽性患者的B/b、B/B、T/t、b/A、B/a、B/A、B/T、B/t、A/t、b/A/T、B/a/T、B/A/T、B/A/t、b/A/t頻率較高。對於併發與未併發肝細胞癌的帶原者,其維生素D受體的頻率分佈相似。維生素D受體的基因多形性與臺灣B型肝炎病毒帶原者的不同臨床表型有關,但與產生肝細胞癌無關。
先天免疫類鐸受體-3的基因變異與慢性B型肝炎有關。我們的目的是探討慢性B型肝炎患者週邊血液單核球細胞與肝臟細胞的類鐸受體-3表現量和接受免疫調節藥物長效型干擾素治療時之變化。我們納入127例慢性B型肝炎患者與64例B型肝炎表面抗原陰性及C型肝炎抗體陰性之控制者。獨立於年齡、性別和ALT值之下 (-13.466,95% 信賴區間 -17.202 –- 9.730,p < 0.001),相較於對照者,慢性B肝病患在週邊血液單核球細胞上有較低的類鐸受體-3平均熒光強度 (14.61 ± 13.49 相較於 9.70 ± 4.61,p < 0.001)。慢性B肝病患的類鐸受體-3免疫組織化學染色主要侷限在庫氏細胞,而控制者的染色散佈在庫氏細胞和肝細胞上。病患的肝臟細胞類鐸受體-3 mRNA表現量也比對照者低 (0.47 ± 0.30倍相較於1倍)。在12例接受長效型干擾素治療的病患中,5例達到持續病毒學反應。使用治療前類鐸受體-3的平均熒光強度為對照,這5例病患之類鐸受體-3的平均熒光強度在治療後立即回升到平均1.5至1.7倍。在七例治療無反應或復發病患中,類鐸受體-3平均熒光強度減少到平均0.5至0.7倍。在10例接受貝樂克治療且具有治療中病毒學反應的患者,在48個星期的治療中,類鐸受體-3平均熒光強度逐漸回升到平均1.2倍。慢性B型肝炎病患之週邊血液單核球細胞上,在獨立的年齡,性別及ALT值之下,以及肝細胞上的類鐸受體-3的表現量降低。長效型干擾素治療而達到持續病毒反應的患者之類鐸受體-3表現的回升較貝樂克治療者更為顯著。
在lamivudine治療中所檢測到的血清HBV RNA是因為RNA的複製中間產物未受藥物治療之影響。我們的目的在於探討慢性B型肝炎患者中免疫調節藥物 (干擾素) 對於血清HBV RNA的抑制效果。血清檢體中的HBV DNA和RNA通過B肝病毒核酸萃取物的逆轉錄和即時PCR而定量之。將對來自以下三組患者之每2週到3個月的檢體進行分析:10名男性患者,接受核苷類似物單一治療44至48週(5名用lamivudine,5名用entecavir);6名男性患者,接受相繼干擾素和lamivudine合併治療;以及3名男性患者,接受lamivudine單一治療20至24週。接受治療前,沒有任何患者血清中檢測到HBV RNA,但在接受治療期間,有15名患者血清中檢測出HBV RNA。在這三組中,治療前HBV DNA (8.1 ± 2.4 相較於 7.7 ± 1.4相較於5.1 ± 0.3 log10 copies/ml,p = 0.06)以及治療和追蹤期間 (45.5 ± 2.0 相較於 49.7 ± 5.6 相較於 48.7 ± 6.4 週,p = 0.32) 相似。HBV RNA 在所有接受單一治療的患者之治療結束時以及追蹤結束時都可檢測到,但在接受相繼合併治療患者中卻沒有一位被檢測到(100% 相較於 0%,p< 0.001)。與lamivudine治療而檢測到血清HBV RNA相比,免疫調節藥物干擾素治療可通過抑制HBV RNA的複製中間產物來降低HBV DNA 的複製,從而使血清HBV RNA消失。

Which host immunogenetic factors and immune receptors correlate with hepatitis severity in chronic hepatitis B (CHB) patients (pts) remain unclear. We aimed to study association of HLA-DRB1 with hepatitis severity in male HBV carriers. 204 HBV carriers (131 men, 73 women) who were followed-up for >1y were enrolled. 50 HBV carriers (group I) with ALT <2x ULN (mean f/u 83.6m) were compared with 154 CHB patients (group II) with ALT ≥2x ULN (mean f/u 81.3m). HLA-DRB1 alleles were typed by PCR-sequence specific oligonucleotide probe hybridization and HBV genotypes by melting curve analysis. HLA-DRB1*1101 was found in 18% of group I vs. 8% of group II in male (OR 0.23, p=0.020, adjusted for age) and 4% vs. 9.4% in female (p=0.094). In male harboring DRB1*1101, distribution of HBV genotype was comparable between 2 groups. HLA-DRB1*1101 correlates with less severe hepatitis in Taiwanese male carriers of HBV.
Vitamin D receptor (VDR) has immunomodulatory and antiproliferative effects. We genotyped BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) of VDR gene in 250 HBV carriers who were categorized into 6 phenotypes. After adjustment for age and sex, frequencies of VDR B/b, B/a, B/T, B/a/T in pts with hepatitis flare(s) were lower than those without (7%vs.20%, p=0.009; 1%vs.9%, p=0.004; 3%vs.10%, p=0.007; 1%vs.9%, p=0.005), in contrast, T/t, A/T, A/t, b/A/t were higher in flare(s) (8% vs. 3%, p=0.003; 49% vs. 34%, p=0.027; 2% vs. 1%, p=0.004; 0.5% vs. 0%, p=0.001). In addition, B/b, B/B, T/t, b/A, B/a, B/A, B/T, B/t, A/t, b/A/T, B/a/T, B/A/T, B/A/t, b/A/t were higher in HBeAg positive pts. Distribution of VDR genotypes was comparable between pts with and without hepatoma. VDR gene polymorphisms are associated with distinct clinical phenotypes but not with hepatoma.
Innate immune receptor toll-like receptor-3 (TLR3) gene variants correlate with CHB. We aimed to investigate TLR3 expression in PBMCs and liver cells of CHB pts and its response to immunomodulation (pegylated-interferon therapy (peg-IFN)). We enrolled 127 CHB pts and 64 HBsAg-negative, anti-HCV negative controls. Compare to controls, pts had a lower TLR3 mean fluorescence intensity (MFI) on PBMCs (14.61 ± 13.49 versus 9.70 ± 4.61, p<0.001), independent of age, gender and ALT (-13.466, 95% CI -17.202 – -9.730, p<0.001). Pts had limited TLR3 stains on Kupffer cells, controls had diffuse stains on Kupffer and hepatocytes. Hepatic TLR3 mRNA was lower in pts than controls (0.47 ± 0.30 versus 1 fold). Using pre-treatment TLR3 MFI as referent, among 5 of 12 peg-IFN treated pts with sustained virological response (SVR), TLR3 MFI restored to a mean of 1.5-1.7 folds immediately after therapy. Among 7 non-responders or relapsers, TLR3 MFI reduced to a mean of 0.5-0.7 fold. Among 10 entecavir (ETV)-treated pts with on-treatment virological response, TLR3 MFI gradually restored to a mean of 1.2 folds during 48-week therapy. CHB pts have reduced TLR3 expressions on PBMCs, independent of age, gender, ALT and on liver cells. Pts with peg-IFN induced SVR have a more significant restoration of TLR3 expression than those under ETV.
Serum HBV RNA is detected during lamivudine therapy as the consequence of unaffected RNA replicative intermediates. We aimed to determine inhibitory effect of immunomodulation (interferon, IFN) on serum HBV RNA in CHB pts. HBV DNA and RNA were quantified by reverse transcription of HBV nucleic acid extract and real-time PCR; every 2 wks to 3m in 10 male treated with nucleoside analogue monotherapy for 44-48wks (5 lamivudine (LMV), 5 ETV), 6 males with sequential IFN and LMV combination, and 3 males with LMV monotherapy for 20-24 wks. HBV RNA was not detectable in all pts before any therapy, but became detectable in 15 during therapy. Among the 3 groups, pretreatment HBV DNA (8.1±2.4 vs. 7.7±1.4 vs. 5.1±0.3 log cp/mL, p=0.06), treatment and follow-up durations (45.5±2.0 vs. 49.7±5.6 vs. 48.7±6.4 wks, p=0.32) were comparable. HBV RNA was detectable at end of therapy or follow-up in all pts with monotherapy, but none of sequential combination (100% vs. 0%, p<0.001). Compared to LMV with detectable serum HBV RNA, immunomodulation of IFN may reduce HBV DNA replication through inhibition of HBV RNA replicative intermediates, resulting in loss of serum HBV RNA.

口試委員會審定書…………………………………………………… 2
誌謝…………………………………………………………………… 6
中文摘要……………………………………………………………… 7
英文摘要……………………………………………………………… 10
博士論文內容
緒論
背景
第一章 B型肝炎病毒感染………………………………………… 14
1.1 B型肝炎病毒學………………………………………… 15
1.2 急性B型肝炎…………………………………………… 15
1.3 慢性B型肝炎…………………………………………… 16
第二章 慢性B型肝炎的免疫遺傳………………………………… 18
2.1 人類白血球抗原………………………………………… 18
2.2 人類白血球抗原與B型肝炎感染……………………… 19
2.3 臺灣族群之人類白血球抗原與B型肝炎感染及慢性
感染的臨床病程……………………………………… 22
第三章 慢性B型肝炎的免疫受體....................... 22
3.1 維生素D免疫受體............................. 22
3.2 先天免疫類鐸受體............................ 24
第四章 慢性B型肝炎的免疫調節....................... 28
研究問題及重要性………………………………………………… 30
研究創新性………………………………………………………… 31
研究的假說與特定目的…………………………………………… 33
研究方法與材料…………………………………………………… 34
病患………………………………………………………………… 34
實驗檢驗項目……………………………………………………… 37
免疫遺傳因子HLA-DRB1對偶基因的訂定、分型及次分型……… 38
維生素D免疫受體基因型和單體型的訂定 ……………………… 38
週邊血液單核球細胞的先天免疫類鐸受體 (TLR)- 3表現量的測定…………………………………………………………………… 39
肝細胞上先天免疫類鐸受體 (TLR)- 3表現量的測定 ………… 39
肝細胞上先天免疫類鐸受體 (TLR)-3免疫組織化學染色……… 40
血清B型肝炎病毒核醣核酸 (HBV RNA) 即時PCR的測定 ……… 41
統計分析…………………………………………………………… 42
結果
ㄧ、免疫遺傳因子HLA-DRB1多形性與男性慢性B型肝炎的肝炎嚴重程度之相關性………………………………………………………… 43
二、維生素D免疫受體基因多形性與慢性B肝的肝炎急性發作、e抗原情況以及肝細胞癌產生之相關性………………………………… 44
三、慢性B型肝炎病患週邊血液單核球細胞和肝臟細胞上先天免疫類鐸受體-3 之表現量,並且其與免疫調節藥物長效型干擾素治療療效
的相關性 ………………………………………………………… 45
四、免疫調節藥物 (干擾素) 對於慢性B肝病患血清病毒核醣核酸
(HBV RNA) 的抑制效果…………………………………………… 48
討論
第ㄧ章 免疫遺傳因子HLA-DRB1多形性與男性慢性B型肝炎的肝炎嚴重程度之相關性…………………………………………………… 50
第二章 維生素D免疫受體基因多形性與慢性B肝的肝炎急性發作、e抗原情況以及肝細胞癌產生之相關性…………………………… 54
第三章 慢性B型肝炎病患週邊血液單核球細胞和肝臟細胞上先天免疫類鐸受體-3 之表現量,並且其與免疫調節藥物長效型干擾素治療療效的相關性…………………………………………………… 60
第四章 免疫調節藥物 (干擾素) 對於慢性B肝病患血清病毒核醣核酸 (HBV RNA) 的抑制效果 …………………………………… 64
展望………………………………………………………………… 70
論文英文簡述 (summary) ……………………………………… 80
參考文獻…………………………………………………………… 91
圖…………………………………………………………………… 120
表…………………………………………………………………… 132
附錄………………………………………………………………… 145

黃奕文、高嘉宏。人類白血球抗原多形性與B型肝炎病毒感染臨床病程之相關性。當代醫學中華民國九十七年五月十五日第三十五卷第五期第344-350頁。
Abe T, Kaname Y, Hamamoto I, et al. Hepatitis C virus nonstructural protein 5A modulates the toll-like receptor-MyD88-dependent signalling pathway in macrophage cell lines. J Virol 2007;81:8953-8966.
Almarri A, Batchelor JR. HLA and hepatitis B infection. Lancet 1994;344:1194-1195.
Al-Qahtani A, Al-Ahdal M, Abdo A, et al. Toll-like receptor 3 polymorphism and its association with hepatitis B virus infection in Saudi Arabian patients. J Med Virol 2012;84:1353-1359.
An P, Winkler C, Guan L, et al. A common HLA-DPA1 variant is a major determinant of hepatitis B virus clearance in Han Chinese. J Infect Dis 2011;203:943-947.
Ank N, Iversen MB, Bartholdy C, et al. An important role for type III interferon (IFN-lambda/IL-28) in TLR-induced antiviral activity. J Immunol 2008;180:2474-2485.
Baker AR, McDonnell DP, Hughes M, et al. Cloning and expression of full-length cDNA encoding human vitamin D receptor. Proc Natl Acad Sci U.S.A. 1988;85:3294-3298.
Barber DL, Wherry EJ, Masopust D, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 2006;439:682-687.
Barrett JC, Fry B, Maller J, et al. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263-265.
Barton GM, Kagan JC. A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat Rev Immunol 2009;9:535-542.
Beckebaum S, Cicinnati VR, Dworacki G, et al. Reduction in the circulating pDC1/pDC2 ratio and impaired function of ex vivo-generated DC1 in chronic hepatitis B infection. Clin Immunol 2002;104:138-150.
Beckebaum S, Cicinnati VR, Zhang X, et al. Hepatitis B virus-induced defect of monocyte-derived dendritic cells leads to impaired T helper type 1 response in vitro: mechanisms for viral immune escape. Immunology 2003;109:487-95.
Bellamy R, Ruwende C, Corrah T, et al. Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene. J Infect Dis 1999;179:721-724.
Benichou G, Takizawa PA, Ho PT, et al. Immunogenicity and tolerogenicity of self-major histocompatibility complex peptides. J Exp Med 1990;172:1341-1346.
Betts MR, Nason MC, West SM, et al. HIV non-progressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 2006;107:4781-4789.
Bjorkman PJ, Saper MA, Samraoui B, et al. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature 1987;329:512-518.
Blackburn SD, Shin H, Haining WN, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 2009;10:29-37.
Bornman L, Campbell SJ, Fielding K, et al. Vitamin D receptor polymorphisms and susceptibility to tuberculosis in West Africa: a case-control and family study. J Infect Dis 2004;190:1631-1641.
Bousfiha A, Picard C, Boisson-Dupuis S, et al. Primary immunodeficiencies of protective immunity to primary infections. Clin Immunol 2010;135:204-209.
Bowie AG, Unterholzner L. Viral evasion and subversion of pattern-recognition receptor signalling. Nat Rev Immunol 2008;8:911-922.
Breiner KM, Schaller H, Knolle PA. Endothelial cell-mediated uptake of a hepatitis B virus: a new concept of liver targeting of hepatotropic microorganisms. Hepatology 2001;34:803-808.
Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42:1208-1236.
Campbell RD, Trowsdale J. Map of the human MHC. Immunol Today 1993;14:349-352.
Carty M, Bowie AG. Recent insights into the role of Toll-like receptors in viral infection. Clin Exp Immunol 2010;161:397-406.
Carty M, Goodbody R, Schroder M, et al. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signalling. Nat Immunol 2006;7:1074-1081.
CDC. Hepatitis B virus: a comprehensive strategy for limiting transmission in the United States through universal childhood vaccination. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40:RR-13:1-25.
Ceppellini R, Frumento G, Ferrara GB, et al. Binding of labeled influenza matrix peptide to HLA DR in living B lymphoid cells. Nature 1989;339:392-394.
Chang CX, Tan AT, Or MY, et al. Conditional ligands for Asian HLA variants facilitate the definition of CD8(+) T-cell responses in acute and chronic viral diseases. Eur J Immunol 2013;43:1109-1120.
Chen BF, Liu CJ, Jow GM, et al. High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases. Gastroenterology 2006; 130:1153-1168.
Chen CJ, Wang LY, Yu MW. Epidemiology of hepatitis B virus infection in the Asia-Pacific region. J Gastroenterol Hepatol 2000;15(Suppl):E3-E6.
Chen DS. From hepatitis to hepatoma: lessons from type B viral hepatitis. Science 1993;262:369-370.
Chen Z, Cheng Y, Xu Y, et al. Expression profiles and function of Toll-like receptors 2 and 4 in peripheral blood mononuclear cells of chronic hepatitis B patients. Clin Immunol 2008;128:400-408.
Cheng HR, Liu CJ, Tseng TC, et al. Host genetic factors affecting spontaneous HBsAg seroclearance in chronic hepatitis B patients. PLoS One 2013;8:e53008.
Chew V, Tow C, Huang C, et al. Toll-like receptor 3 expressing tumor parenchyma and infiltrating natural killer cells in hepatocellular carcinoma patients. J Natl Cancer Inst 2012;104:1796-1807.
Chisari FV. Cytotoxic T cells and viral hepatitis. J Clin Invest 1997;99:1472-1477.
Chisari FV, Ferrari C. Hepatitis B immunopathogenesis. Annu Rev Immunol 1995;13:29-60.
Chu CM. Natural history of chronic hepatitis B virus infection in adults with emphasis on the occurrence of cirrhosis and hepatocellular carcinoma. J Gastroenterol Hepatol 2000;15(Suppl):E25-30.
Chu CM, Hung SJ, Lin J, et al. Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels. Am J Med 2004;116:829-834.
Chu CM, Liaw YF. HBsAg seroclearance in asymptomatic carriers of high endemic areas: Appreciably high rates during a long-term follow-up. Hepatology 2007a;45:1187-1192.
Chu CM, Liaw YF. Predictive factors for reactivation of hepatitis B following hepatitis B e antigen seroconversion in chronic hepatitis B. Gastroenterology 2007b;133:1458-1465.
Chu CM, Liaw YF, Sheen IS, et al. Sex difference in chronic hepatitis B virus infection: an appraisal based on the status of hepatitis B e antigen and antibody. Hepatology 1983;3:947-950.
Coffin CS, Michalak TI. Persistence of infectious hepadnavirus in the offspring of woodchuck mothers recovered from viral hepatitis. J Clin Invest 1999;104:203-212.
Cramp ME, Carucci P, Underhill J, et al. Association between HLA class II genotype and spontaneous clearance of hepatitis C viraemia. J Hepatol 1998;29:207-213.
Dalhoff K, Dancey J, Astrup L, et al. A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma. Br J Cancer 2003;89:252-257.
Delaloye J, Roger T, Steiner-Tardivel QG, et al. Innate immune sensing of modified vaccinia virus Ankara (MVA) is mediated by TLR2-TLR6, MDA-5 and the NALP3 inflammasome. PLoS Pathog 2009;5:e1000480.
Dienstag JL. Hepatitis B virus infection. N Engl J Med 2008;359:1486-1500.
Doong SL, Tsai CH, Schinazi RF, et al. Inhibition of the replication of hepatitis B virus in vitro by 2’,3’-dideoxy-3’-thiacytidine and related analogues. Proc Natl Acad Sci USA 1991;88:8495-8499.
Durrin LK, Haile RW, Ingles SA, et al. Vitamin D receptor 3’-untranslated region polymorphisms: lack of effect on mRNA stability. Biochem Biophys Acta 1999;1453:311-320.
Elahi S, Horton H. Association of HLA-alleles with the immune regulation of chronic viral infections. Int J Biochem Cell Biol 2012;44:1361-1365.
Forzani B, Actis GC, Verme G, et al. HLA-DR antigens in HBsAg-positive chronic active liver disease with and without associated delta infection. Hepatology 1984;4:1107-1110.
Foster GR, Ackrill AM, Goldin RD, et al. Expression of the terminal protein region of hepatitis B virus inhibits cellular responses to interferons alpha and gamma and double-stranded RNA. Proc Natl Acad Sci USA 1991;88:2888-2892.
Ganem D, Varmus HE. The molecular biology of the hepatitis B viruses. Ann Rev Biochem 1987;56:651-693.
Genesca M. Characterization of an effective CTL response against HIV and SIV infections. J Biomed Biotechnol 2011;2011:103924.
Gerelsaikhan T, Tavis JE, Bruss V. Hepatitis B virus nucleocapsid envelopment does not occur without genomic DNA synthesis. J Virol 1996;70:4269-4274.
Gill N, Deacon PM, Lichty B, et al. Induction of innate immunity against herpes simplex virus type 2 infection via local delivery of Toll-like receptor ligands correlates with beta interferon production. J Virol 2006;80:9943-9950.
Gowen BB, Wong MH, Jung KH, et al. TLR3 is essential for the induction of protective immunity against Punta Toro Virus infection by the double-stranded RNA (dsRNA), poly(I:C12U), but not Poly(I:C): differential recognition of synthetic dsRNA molecules. J Immunol 2007;178:5200-5208.
Guo X, Zhang Y, Li J, et al. Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population. Hepatology 2011;53:422-428.
Hann HW, Hann RS, Maddrey WC. Hepatitis B virus infection in 6,130 unvaccinated Korean-Americans surveyed between 1988 and 1990. Am J Gastroenterol 2007;102:767-772.
Hatakeyama T, Noguchi C, Hiraga N, et al. Serum HBV RNA is a predictor of early emergence of the YMDD mutant in patients treated with lamivudine. Hepatology 2007;45:1179-1186.
Hattum JV, Schreuder GT, Schalm SW. HLA antigens in patients with various courses after hepatitis B virus infection. Hepatology 1987;7:11-14.
Haussler MR, Whitfield GK, Haussler CA, et al. The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 1998;13:325-349.
Hayes CE, Nashold FE, Spach KM, et al. The immunological functions of the vitamin D endocrine system. Cell Mol Biol 2003;49:277-300.
Heiberg IL, Winther TN, Paludan SR, et al. Pattern recognition receptor responses in children with chronic hepatitis B virus infection. J Clin Virol 2012;54:229-234.
Hidaka F, Matsuo S, Muta T, et al. A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy. Clin Immunol 2006;119:188-194.
Hohler T, Gerken G, Notghi A, et al. HLA-DRB1*1301 and *1302 protect against chronic hepatitis B. J Hepatol 1997;26:503-507.
Hohler T, Meyer CU, Notghi A, et al. The influence of major histocompatibility complex class II genes and T-cell Vβ repertoire on response to immunization with HBsAg. Hum Immunol 1998;59:212-218.
Hornung V, Ablasser A, Charrel-Dennis M et al. AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 2009;458:514-18.
Horton H, Frank I, Baydo R, et al. Preservation of T cell proliferation restricted by protective HLA alleles is critical for immune control of HIV-1 infection. J Immunol 2006;177:7406-7415.
Howell MD, Gallo RL, Boguniewicz M, et al. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity 2006;24:341-348.
Huang YW, Chayama K, Tsuge M, et al. Serum HBV RNA level reflects the potency of nucleos(t)ide analogue. Hepatol Int 2009;3:110. (Abstract)
Huang YW, Chung RT. Management of hepatitis B reactivation in patients receiving cancer chemotherapy. Therap Adv Gastroenterol 2012;5:359-370.
Huang YW, Hu JT, Chang HY, et al. Predictors of response in adefovir combination to lamivudine for lamivudine resistant HBeAg positive and negative chronic hepatitis B. Hepatol Int 2012a;6:134-135. (Abstract)
Huang YW, Hu JT, Hu FC, et al. Biphasic pattern of depression and its predictors during pegylated interferon-based therapy in chronic hepatitis B and C patients. Antivir Ther 2012b Oct 17. doi: 10.3851/IMP2441 (In press).
Huang YW, Lin CL, Chen PJ, et al. Higher cut-off index value of immunoglobulin M antibody to hepatitis B core antigen in Taiwanese patients with hepatitis B. J Gastroenterol Hepatol 2006a;21:859-862.
Huang YW, Lin CL, Chen PJ, et al. Hepatitis B viral genotype in Taiwanese patients with acute hepatitis B. Hepato-Gastroenterology 2008a;55:633-635.
Huang YW, Liu CJ, Lai MY, et al. Discontinuation of lamivudine treatment for hepatitis flare after kidney or heart transplant in hepatitis B surface antigen positive patients: a retrospective case series. Clin Ther 2006b;28:1327-1334.
Huang YW, Takahashi S, Tsuge M, et al. Presence of serum HBV RNA predicts initial virological response in nucleoside analogue treated chronic hepatitis B patients. Hepatology 2012c;56:422A (Abstract).
Huang YW, Tsuge M, Takahashi S, et al. Interferon inhibits HBV RNA detected during lamivudine therapy. J Hepatol 2008b;48:S244. (Abstract)
Huang YW, Wang TC, Hu JT, et al. Increased risk of cirrhosis in chronic hepatitis B patients who develop diabetes: A population-based study. Hepatology 2011;54:446A. (Abstract)
Huo T, Wu JC, Hwang SJ, et al. Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a multivariate analysis in a longitudinal study. Eur J Gastroenterol Hepatol 2000;12:687-693.
Iloeje UH, Yang HI, Su J, et al. Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006;130:678-686.
Isogawa M, Robek MD, Furuichi Y, et al. Toll-like receptor signaling inhibits hepatitis B virus replication in vivo. J Virol 2005;79:7269-72.
Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004;5:987-995.
Janeway CA, Jr. The immune system evolved to discriminate infectious nonself from noninfectious self. Immunol Today 1992;13:11-16.
Jiang YG, Wang YM, Liu TH, et al. Association between HLA class II gene and susceptibility or resistance to chronic hepatitis B. World J Gastroenterol 2003;9:2221-2225.
Kamatani Y, Wattanapokayakit S, Ochi H, et al. A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nat Genet 2009;41:591-5.
Kamisango K, Kamogawa C, Sumi M, et al. Quantitative detection of hepatitis B virus by transcription-mediated amplification and hybridization protection assay. J Clin Microbiol 1999;37:310-314.
Kao JH. Role of viral factors in the natural course and therapy of chronic hepatitis B. Hepatol Int 2007;1:415-430.
Kao JH, Chen DS. Overview of hepatitis B and C viruses. In: Goedert JJ, ed. Infectious Causes of Cancer: Targets for Intervention. Totowa: Humana Press Inc. 2000;313-330.
Kao JH, Chen DS. Global control of hepatitis B virus infection. Lancet Infect Dis 2002;2:395–403.
Kao JH, Chen PJ, Lai MY, et al. Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B. Gastroenterology 2000;118:554-559.
Kao JH, Chen PJ, Lai MY, et al. Acute exacerbations of chronic hepatitis B are rarely associated with superinfection of hepatitis B virus. Hepatology 2001;34:817-823.
Kao JH, Chen PJ, Lai MY, et al. Genotypes and clinical phenotypes of hepatitis B virus in patients with chronic hepatitis B virus infection. J Clin Microbiol 2002;40:1207-1209.
Kaufmann DE, Kavanagh DG, Pereyra F, et al. Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat Immunol 2007;8:1246-1254.
Kawai T, Akira S. The roles of TLRs, RLRs and NLRs in pathogen recognition. Int Immunol 2009;21:317-337.
Kock J, Theilmann L, Galle P, et al. Hepatitis B virus nucleic acids associated with human peripheral blood mononuclear cells do not originate from replicating virus. Hepatology 1996;23:405-413.
Kumar H, Kawai T, Akira S. Toll-like receptors and innate immunity. Biochem Biophys Res Commun 2009;388:621-625.
Labuda M, Fujiwara TM, Ross MV, et al. Two hereditary defects related to vitamin D metabolism map to the same region of human chromosome 12q13-14. J Bone Miner Res 1992;7:1447-1453.
Lai Y, Yi G, Chen A, et al. Viral double-strand RNA-binding proteins can enhance innate immune signaling by Toll-like receptor 3. PLoS One 2011;6:e25837.
Lambotin M, Raghuraman S, Stoll-Keller F, et al. A look behind closed doors: interaction of persistent viruses with dendritic cells. Nat Rev Microbiol 2010;8:350-360.
Lau GK, Piratvisuth T, Luo KX, et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 2005;352:2682-2695.
Lau YF, Tang LH, Ooi EE. A TLR3 ligand that exhibits potent inhibition of influenza virus replication and has strong adjuvant activity has the potential for dual applications in an influenza pandemic. Vaccine 2009;27:1354-1364.
Lee W. Hepatitis B virus infection. N Engl J Med 1997;337:1733-1745.
Lengyel P. Mechanisms of interferon action: the 2’5’ A synthetase-RNase L pathway. In Interferon 3. Edited by I Gresser. New York: Academic Press 1981;pp. 77-99.
Lew YY, Michalak TI. In vitro and in vivo infectivity and pathogenecity of the lymphoid cell-derived woodchuck hepatitis virus. J Virol 2001;75:1770-1782.
Li J, Yang D, He Y, et al. Associations of HLA-DP variants with hepatitis B virus infection in Southern and Northern Han Chinese populations: A multicenter case-control study. PLoS One 2011;6:e24221.
Li JH, Chen DM, Li Z, et al. Study on association between vitamin D receptor gene polymorphisms and the outcomes of HBV infection. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2006a;23:402-405.
Li JH, Li HQ, Li Z, et al. Association of TaqI T/C and FokI C/T polymorphisms of vitamin D receptor gene with outcome of hepatitis B virus infection. Zhonghua Yi Xue Za Zhi 2006b;86:1952-1956.
Li K, Foy E, Ferreon JC, et al. Immune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF. Proc Natl Acad Sci USA 2005;102:2992-2997.
Li N, Li Q, Qian Z, et al. Impaired TLR3/IFN-beta signaling in monocyte-derived dendritic cells from patients with acute-on-chronic hepatitis B liver failure: relevance to the severity of liver damage. Biochem Biophys Res Commun 2009;390:630-635.
Liang TJ. Hepatitis B: the virus and disease. Hepatology 2009;49:S13-21.
Lin CL, Liao LY, Wang CS, et al. Basal core-promoter mutant of hepatitis B virus and progression of liver disease in hepatitis B e antigen-negative chronic hepatitis B. Liver Int 2005;25:564-570.
Lin KW, Kirchner JT. Hepatitis B. Am Fam Physician 2004;69:75-82.
Liu CJ, Liou JM, Chen DS, et al. Natural course and treatment of dual hepatitis B virus and hepatitis C virus infections. J Formos Med Assoc 2005;104:783-791.
Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006;311:1770-1773.
Lok ASF, McMahon BJ. Chronic hepatitis B. Hepatology 2007;45:507-539.
Maloney G, Schroder M, Bowie AG. Vaccinia virus protein A52R activates p38 mitogen-activated protein kinase and potentiates lipopolysaccharide-induced interleukin-10. J Biol Chem 2005;280:30838-30844.
Marcellin P, Lau GK, Bonino F, et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med 2004;351:1206-1217.
Martin MP, Carrington M. Immunogenetics of viral infections. Curr Opin Immunol 2005;17:510-516.
Matsumoto M, Seya T. TLR3: interferon induction by double-stranded RNA including poly(I:C). Adv Drug Deliv Rev 2008;60:805-812.
Mbarek H, Ochi H, Urabe Y, et al. A genome-wide association study of chronic hepatitis B identified novel risk locus in a Japanese population. Hum Mol Genet 2011;20:3884-92.
McClary H, Koch R, Chisari FV, et al. Relative sensitivity of hepatitis B virus and other hepatotropic viruses to the antiviral effects of cytokines. J Virol 2000;74:2255-2264.
McQuillan GM, Townsend TR, Fields HA, et al. Seroepidemiology of hepatitis B virus infection in the United States. Am J Med 1989;87(suppl 3A): 5S-10S.
Migueles SA, Osborne CM, Royce C, et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity 2008;29:1009-1021.
Milich DR, Wolf SF, Hughes JL, et al. Interleukin 12 suppresses autoantibody production by reversing helper T-cell phenotype in hepatitis B e antigen transgenic mice. Proc Natl Acad Sci USA 1995;92:6874-51.
Miyamoto K, Kesterson RA, Yamamoto H, et al. Structural organization of the human vitamin D receptor chromosomal gene and its promoter. Mol Endocrinol 1997;11:1165-1179.
Morrison NA, Qi JC, Tokita A, et al. Prediction of bone density from vitamin D receptor alleles. Nature 1994;367:284-287.
Mota AH, Fainboim H, Terg R, et al. Association of chronic active hepatitis and HLA B35 in patients with hepatitis B virus. Tissue Antigens 1987;30:238-240.
Nahum A, Dadi H, Bates A, et al. The L412F variant of Toll-like receptor 3 (TLR3) is associated with cutaneous candidiasis, increased susceptibility to cytomegalovirus, and autoimmunity. J Allergy Clin Immunol 2011;127:528-531.
Netea MG, van der Meer JW. Immunodeficiency and genetic defects of pattern-recognition receptors. N Engl J Med 2011;364:60-70.
Neumann-Haefelin C, McKiernan S, Ward S, et al. Dominant influence of an HLA-B27 restricted CD8+ T cell response in mediating HCV clearance and evolution. Hepatology 2006;43:563-572.
O’Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 2007;7:353-364.
Pasquetto V, Wieland SF, Uprichard SL, et al. Cytokine-sensitive replication of hepatitis B virus in immortalized mouse hepatocyte cultures. J Virol 2002;76:5646-5653.
Penna A, Del Prete G, Cavalli A, et al. Predominant T-helper 1 cytokine profile of hepatitis B virus nucleocapsid-specific T cells in acute self-limited hepatitis B. Hepatology 1997;25:1022-1027.
Poonia B, Pauza CD, Salvato MS. Role of the Fas/FasL pathway in HIV or SIV disease. Retrovirology 2009;6:91.
Porterfield JZ, Dhason MS, Loeb DD, et al. Full-length hepatitis B virus core protein packages viral and heterologous RNA with similarly high levels of cooperativity. J Virol 2010;84:7174-7184.
Potter DM. A permutation test for inference in logistic regression with small- and moderate-sized data sets. Stat Med 2005;24:693-708.
Pourgholami MH, Akhter J, Ku Y, et al. In vitro and in vivo inhibition of liver cancer cells by 1,25-dihydroxyvitamin D3. Cancer Lett 2000;151:97-102.
Pourgholami MH, Morris DL. 1,25-dihydroxyvitamin D3 in lipiodol for the treatment of hepatocellular carcinoma: cellular, animal and clinical studies. J Steroid Biochem Mol Biol 2004;89-90:513-518.
Ranjith-Kumar CT, Miller W, Xiong J, et al. Biochemical and functional analyses of the human Toll-like receptor 3 ectodomain. J Biol Chem 2007;282:7668-7678.
Realdi G, Fattovich G, Hadziyannis S, et al. Survival and prognostic factors in 366 patients with compensated cirrhosis type B: a multicenter study. J Hepatol 1994;21:656-666.
Riggs BL, Nguyen TV, Melton III LJ, et al. The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic woman. J Bone Miner Res 1995;10:991-996.
Risch N, Merikangas K. The future of genetic studies of complex human diseases. Science 1996;273:1516-1517.
Rokuhara A, Matsumoto A, Tanaka E, et al. Hepatitis B virus RNA is measurable in serum and can be a new marker for monitoring lamivudine therapy. J Gastroenterol 2006;41:785-790.
Rong Y, Song H, You S, et al. Association of Toll-like receptor 3 polymorphisms with chronic hepatitis B and hepatitis B-related acute-on-chronic liver failure. Inflammation 2012;doi:10.1007/s10753-012-9560-4. Published online: 18 October 2012.
Rouse BT, Sehrawat S. Immunity and immunopathology to viruses: what decides the outcome? Nat Rev Immunol 2010;10:514-526.
Roy CR, Mocarski ES. Pathogen subversion of cell-intrinsic innate immunity. Nat Immunol 2007;8:1179-1187.
Saez-Cirion A, Lacabaratz C, Lambotte O, et al. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc Natl Acad Sci USA 2007;104:6776-6781.
Sarin SK, Kumar M, Kumar R, et al. Higher efficacy of sequential therapy with interferon-alpha and lamivudine combination compared to lamivudine monotherapy in HBeAg positive chronic hepatitis B patients. Am J Gastroenterol 2005;100:2463-2471.
Sato A, Linehan MM, Iwasaki A. Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells. Proc Natl Acad Sci USA 2006;103:17343-17348.
Scharf JS, Griffith RL, Erlich HA. Rapid typing of DNA sequence polymorphism at the HLA-DRB1 locus using the polymerase chain reaction and nonradioactive oligonucleotide probes. Human Immunol 1991;30:190-201.
Schoenberger SP, Toes RE, van der Voort EI, et al. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature 1998;393:480-483.
Schulz O, Diebold SS, Chen M, et al. Toll-like receptor 3 promotes cross-priming to virus-infected cells. Nature 2005;433:887-892.
Schurich A, Khanna P, Lopes AR, et al. Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-prone CD8T cells in persistent hepatitis B virus infection. Hepatology 2011;53:1494-1503.
Shiffman ML, Stewart CA, Hofmann CM, et al. Chronic infection with hepatitis C virus in patients with elevated or persistently normal serum alanine aminotransferase levels: comparison of hepatic histology and response to interferon therapy. J Infect Dis 2000;182:1595-1601.
Shin H, Wherry EJ. CD8T cell dysfunction during chronic viral infection. Curr Opin Immunol 2007;19:408-415.
Singh R, Kaul R, Kaul A, et al. A comparative review of HLA associations with hepatitis B and C viral infections across global populations. World J Gastroenterol 2007;13:1770-1787.
Sonneveld MJ, Arends P, Boonstra A, et al. Serum levels of interferon-gamma-inducible protein 10 and response to peginterferon therapy in HBeAg-positive chronic hepatitis B. J Hepatol 2013 Jan 29. pii: S0168-8278(13)0076-7. doi: 10.1016/j.hep.2013.01.029.
Sorensen LN, Reinert LS, Malmgaard L, et al. TLR2 and TLR9 synergistically control herpes simplex virus infection in the brain. J Immunol 2008;181:8604-8612.
Stack J, Haga IR, Schroder M, et al. Vaccinia virus protein A46R targets multiple Toll-like interleukin-1 receptor adaptors and contributes to virulence. J Exp Med 2005;201:1007-1018.
Stark GR, Kerr IM, Williams BR, et al. How cells respond to interferons. Annu Rev Biochem 1998;67:227-264.
Stevens CE, Beasley RP, Tsui J, et al. Vertical transmission of hepatitis B antigen in Taiwan. N Engl J Med 1975;292:771-774.
Su Q, Wang SF, Chang TE, et al. Circulating hepatitis B virus nucleic acids in chronic infection: representation of differently polyadenylated viral transcripts during progression to nonreplicative stages. Clin Cancer Res 2001;7:2005-2015.
Suneetha PV, Sarin SK, Goyal A, et al. Association between vitamin D receptor, CCR5, TNF-α and TNF-β gene polymorphisms and HBV infection and severity of liver disease. J Hepatol 2006;44:856-863.
Sung JJ, Wong ML, Bowden S, et al. Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy. Gastroenterology 2005;128:1890-1897.
Takeuchi O, Akira S. Innate immunity to virus infection. Immunol Rev 2009;227:75-86.
Tamura I, Kurimura O, Koda T, et al. Risk of liver cirrhosis and hepatocellular carcinoma in subjects with hepatitis B and delta virus infection: a study from Kure, Japan. J Gastroenterol Hepatol 1993;8:433-436.
Tang TJ, Kwekkeboom J, Laman JD, et al. The role of intrahepatic immune effector cells in inflammatory liver injury and viral control during chronic hepatitis B infection. J Viral Hepat 2003;10:159-167.
Taymans SE, Pack S, Pak E, et al. The human vitamin D receptor gene (VDR) is localized to region 12cen-q12 by fluorescent in situ hybridization and radiation hybrid mapping: genetic and physical VDR map. J Bone Miner Res 1999;14:1163-1166.
Thio CL, Carrington M, Marti D, et al. Class II HLA alleles and hepatitis B virus persistence in African Americans. J Infect Dis 1999;179:1004-1006.
Thio CL, Thomas DL, Karacki P, et al. Comprehensive analysis of class I and class II HLA antigens and chronic hepatitis B virus infection. J Virol 2003;77:12083-12087.
Thomas H, Foster G, Platis D. Mechanisms of action of interferon and nucleoside analogues. J Hepatol 2003;39:S93-98.
Thursz M, Yallop R, Goldin R, et al. Influence of MHC class II genotype on outcome of infection with hepatitis C virus. The HENCORE group. Hepatitis C European Network for Cooperative Research. Lancet 1999;354:2119-2124.
Thursz MR, Kwiatkowski D, Allsopp CEM, et al. Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia. N Engl J Med 1995;332:1065-1069.
Tiwari JL, Terasaki PI. HLA and disease associations. Heidelberg, Germany: Springer-Verlag 1989;31-169.
Tjwa ET, van Oord GW, Biesta PJ, et al. Restoration of TLR3-activated myeloid dendritic cell activity leads to improved natural killer cell function in chronic hepatitis B virus infection. J Virol 2012;86:4102-4109.
Tsuge M, Murakami E, Imamura M, et al. Serum HBV RNA and HBeAg are useful markers for the safe discontinuation of nucleotide analogue treatments in chronic hepatitis B patients. J Gastroenterol 2013 Feb 9 [Epub ahead of print].
Uematsu S, Akira S. Toll-like receptors and Type I interferons. J Biol Chem 2007;282:15319-15323.
Uitterlinden AG, Fang Y, van Meurs JBJ, et al. Genetics and biology of vitamin D receptor polymorphisms. Gene 2004;338:143-156.
Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 2006;371:1-12.
van der Molen RG, Sprengers D, Binda RS, et al. Functional impairment of myeloid and plasmacytoid dendritic cells of patients with chronic hepatitis B. Hepatology 2004;40:738-46.
van Etten E, Mathieu C. Immunoregulation by 1,25-dihydroxyvitamin D3: basic conocepts. J Steroid Biochem Mol Biol 2005;97:93-101.
van Hattum J, Schreuder GM, Schalm SW. HLA antigens in patients with various courses after hepatitis B virus infection. Hepatology 1987;7:11-14.
Veldman CM, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system. Arch Biochem Biophys 2000;374:334-338.
Vermehren J, Lotsch J, Susser S, et al. A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers. PLoS One 2012;7:e32605.
Visvanathan K, Skinner NA, Thompson AJV, et al. Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the precore protein. Hepatology 2007;45:102-10.
Wang K, Liu H, He Y, et al. Correlation of TLR1-10 expression in peripheral blood mononuclear cells with chronic hepatitis B and chronic hepatitis B-related liver failure. Hum Immunol 2010;71:950-956.
Wang L, Wu XP, Zhang W, et al. Evaluation of genetic susceptibility loci for chronic hepatitis B in Chinese: two independent case-control studies. PLoS One 2011;6:e17608.
Wasley A, Miller JT, Finelli L. CDC. Surveillance for acute viral hepatitis—United States, 2005. MMWR. Surveillance Summaries. 2007;56:1-24.
Wieland SF, Guidotti LG, Chisari FV. Intrahepatic induction of alpha/beta interferon eliminates viral RNA-containing capsids in hepatitis B virus transgenic mice. J Virol 2000;74:4165-4173.
Woltman AM, Op den Brouw ML, Biesta PJ, et al. Hepatitis B virus lacks immune activating capacity, but actively inhibits plasmacytoid dendritic cell function. PLoS One 2011;6:e15324.
Wong DK, Yuen MF, Yuan H, et al. Quantification of covalently closed circular hepatitis B virus DNA in chronic hepatitis B patients. Hepatology 2004;40:727-737.
Wong JP, Christopher ME, Viswanathan S, et al. Antiviral role of toll-like receptor-3 agonists against seasonal and avian influenza viruses. Curr Pharm Des 2009;15:1269-1274.
Wu J, Lu M, Meng Z, et al. Toll-like receptor-mediated control of HBV replication by nonparenchymal liver cells in mice. Hepatology 2007;46:1769-1778.
Wu J, Meng Z, Jiang M, et al. Hepatitis B virus suppresses Toll-like receptor-mediated innate immune responses in murine parenchymal and nonparenchymal liver cells. Hepatology 2009;49:1132-1140.
Wu JF, Chen CH, Hsieh RP, et al. HLA typing associated with hepatitis B e antigen seroconversion in children with chronic hepatitis B virus infection: a long-term prospective sibling cohort study in Taiwan. J Pediatr 2006;148:647-651.
Wu YF, Wang LY, Lee TD, et al. HLA phenotypes and outcomes of hepatitis B virus infection in Taiwan. J Med Virol 2004;72:17-25.
Xie Q, Shen HC, Jia NN, et al. Patients with chronic hepatitis B infection display deficiency of plasmacytoid dendritic cells with reduced expression of TLR9. Microbes Infect 2009;11:515-523.
Xu Y, Hu Y, Shi B, et al. HBsAg inhibits TLR9-mediated activation and IFN-alpha production in plasmacytoid dendritic cells. Mol Immunol 2009;46:2640-2646.
Yanai H, Savitsky D, Tamura T, et al. Regulation of the cytosolic DNA-sensing system in innate immunity: a current view. Curr Opin Immunol 2009;21:17-22.
Yang PM, Sung JL, Chen DS. HLA-A,B,C and DR antigens in chronic hepatitis B viral infection. Hepato-Gastroenterology 1989;36:363-366.
Yeh SH, Tsai CY, Kao JH, et al. Quantification and genotyping of hepatitis B virus in a single reaction by real-time PCR and melting curve analysis. J Hepatol 2004;41:659-666.
Yokota S, Okabayashi T, Fujii N. The battle between virus and host: modulation of Toll-like receptor signaling pathways by virus infection. Mediators Inflamm 2010;2010:184328.
Yoneyama M, Fujita T. Recognition of viral nucleic acids in innate immunity. Rev Med Virol 2010;20:4-22.
Yu S, Chen J, Wu M, et al. Hepatitis B virus polymerase inhibits RIG-I- and Toll-like receptor 3-mediated beta interferon induction in human hepatocytes through interference with interferon regulatory factor 3 activation and dampening of the interaction between TBK1/IKKepsilon and DDX3. J Gen Virol 2010;91:2080-2090.
Yu YS, Tang ZH, Han JC, et al. Expression of ICAM-I, HLA-DR, and CD80 on peripheral circulating CD1 alpha DCs induced in vivo by IFN-alpha in patients with chronic hepatitis B. World J Gastroenterol 2006;12:1447-1451.
Yuen MF, Wong DK, Sum SS, et al. Effect of lamivudine therapy on the serum covalently closed-circular (ccc) DNA of chronic hepatitis B infection. Am J Gastroenterol 2005;100:1099-1103.
Zhang W, Hacker HJ, Tokus M, et al. Patterns of circulating hepatitis B virus serum nucleic acids during lamivudine therapy. J Med Virol 2003;71:24-30.
Zhang SY, Jouanguy E, Ugolini S, et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science 2007;317:1522-1527.
Zheng BJ, Zhou J, Qu D, et al. Selective functional deficit in dendritic cell – T cell interaction is a crucial mechanism in chronic hepatitis B virus infection. J Viral Hepat 2004;11:217-24.
Zmuda JM, Cauley JA, Ferrell RE. Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev 2000;22:203-217.
Zucchini N, Bessou G, Traub S, et al. Cutting edge: overlapping functions of TLR7 and TLR9 for innate defense against a herpes-virus infection. J Immunol 2008;180:5799-5803.

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