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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 蕭朱杏(Chuhsing Kate Hsiao) | |
dc.contributor.author | Jessica Liu | en |
dc.contributor.author | 劉薇真 | zh_TW |
dc.date.accessioned | 2021-06-16T16:29:15Z | - |
dc.date.available | 2013-03-04 | |
dc.date.copyright | 2013-03-04 | |
dc.date.issued | 2012 | |
dc.date.submitted | 2013-01-03 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63225 | - |
dc.description.abstract | Background and Aims: The natural history of chronic hepatitis B infection is defined by three distinct phases, characterized by time-dependent interactions between hepatitis B e antigen (HBeAg), serum HBV DNA, and hepatitis B surface antigen (HBsAg). Recently, serum levels of HBsAg have been suggested as a new biomarker for monitoring immunological response in chronic hepatitis B infection. The first and second aims of this dissertation are to examine the role of quantitative HBsAg levels, and to determine if they are able to improve the predictability of HBeAg, HBV DNA, and HBsAg seroclearance. The third aim is to examine the association between seroclearance of HBeAg, HBV DNA, and HBsAg and the reduction in risk for hepatocellular carcinoma, using time-dependent Cox proportional hazards models.
Methods: HBsAg seropositive individuals who were Anti-HCV seronegative and free of liver cirrhosis at study entry were included in analyses. Prediction models were derived from multivariate Cox proportional hazards models, and predictive accuracy was assessed using receiver operating characteristic (ROC) curves. To assess HCC risk, additional time-dependent Cox proportional hazards models were used. Results: Examining HBeAg and HBV DNA seroclearance showed that HBsAg levels were not able to predict HBeAg seroclearance. However, HBsAg levels were able increase predictability of HBV DNA seroclearance, although predictive accuracy was still only moderate. The AUROC for five-year and ten-year prediction of HBV DNA seroclearance after addition of HBsAg levels increased from 0.62 (0.58-0.66) to 0.75 (0.70-0.80), and 0.61 (0.58-0.64) to 0.73 (0.70-0.76), respectively. In addition, HBsAg levels were the most significant predictor of HBsAg seroclearance, even after adjustment for HBV DNA levels. The addition of HBsAg levels into the prediction model significantly increased the predictive accuracy for both five- and ten-year prediction. The AUROC for five-year and ten-year prediction of HBsAg seroclearance after addition of HBsAg levels increased from 0.79 (0.76-0.82) to 0.89 (0.87-0.91), and from 0.73 (0.70-0.76) to 0.84 (0.81-0.87), respectively. For HCC risk reduction, results among 2968 individuals showed that HBV DNA seroclearance was the most important predictor of the reduced risk for hepatocellular carcinoma, especially among individuals with high viral loads, even after adjusting for HBeAg and HBsAg seroclearance, as well as baseline HBV DNA levels. Conclusion: This dissertation has further elucidated the roles of seromarkers in the natural history of chronic hepatitis B infection, and has also confirmed the importance of considering quantitative HBsAg levels in addition to HBV DNA levels. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T16:29:15Z (GMT). No. of bitstreams: 1 ntu-101-D99849019-1.pdf: 3048985 bytes, checksum: 388e510daa682055c3e223c3191ae568 (MD5) Previous issue date: 2012 | en |
dc.description.tableofcontents | Acknowledgments i
Abstract ii List of Figures vii List of Tables ix Chapter 1: Introduction 1 1.1 Introduction to chronic hepatitis B virus infection 1 1.1.1 Clinical consequences of chronic hepatitis B virus infection 1 1.1.2 Hepatitis B virus 2 1.2 Natural history of chronic hepatitis B virus infection 3 1.2.1 Stages of disease and interactions with seromarkers 3 1.2.2 Roles of HBeAg, HBV DNA level, and HBsAg 4 1.3 Current treatment methods for chronic hepatitis B virus infection 6 1.4 Recent advances in hepatitis B research: quantitative hepatitis B surface antigen 8 1.4.1 Interest in quantitative hepatitis B surface antigen 8 1.4.2 Role of quantitative hepatitis B surface antigen 9 1.4.3 Prediction of treatment response, serological, and clinical outcomes 12 1.5 Specific aims and hypotheses 13 Chapter 2: Materials and Methods 15 2.1 Study population and areas 15 2.2 Treatment history of study participants 16 2.3 Baseline and follow-up visit procedures 17 2.4 Laboratory methods 17 2.4.1 HBsAg quantification methods 18 2.5 Ascertainment of outcomes 18 2.6 Statistical methods 19 2.6.1 Univariate and multivariate methods 19 2.6.2 Score-based prediction method 20 2.6.3 Prediction accuracy 21 2.7 Serum HBsAg and HBV DNA Levels in the R.E.V.E.A.L.-HBV Cohort 23 Chapter 3: Quantitative Serum Hepatitis B Surface Antigen Levels Improve the Predictability of HBV DNA but not HBeAg Seroclearance in Chronic Hepatitis B Patients 25 Abstract 25 3.1 Introduction 26 3.2 Methods 27 3.2.1 Study Cohort 27 3.2.2 Data Collection and Laboratory Methods 28 3.2.3 Ascertainment of Outcomes 29 3.2.4 Statistical Analysis 29 3.2.5 Development of Prediction Models for HBV DNA Seroclearance 30 3.3 Results 30 3.3.1 Baseline Characteristics 30 3.3.2 Determinants of Spontaneous HBeAg Seroclearance 30 3.3.3 Determinants of Spontaneous HBV DNA Seroclearance 31 3.3.4 Multivariate Regression Models for Spontaneous HBV DNA Seroclearance 32 3.3.5. Long-Term Tracking of HBsAg Levels Prior to HBV DNA Seroclearance 33 3.4 Discussion and Conclusion 34 Chapter 4: A Predictive Scoring System for the Seroclearance of HBsAg in HBeAg-seronegative Chronic Hepatitis B Patients with Genotype B or C Infection 51 Abstract 51 4.1 Introduction 52 4.2 Methods 53 4.2.1 Study Cohort 53 4.2.2 Data Collection and Laboratory Methods 54 4.2.3 Ascertainment of Spontaneous HBsAg Seroclearance 55 4.2.4 Statistical Analysis 55 4.2.5 Development of Prediction Models of Spontaneous HBV Eradication 56 4.2.6 Measurement of Prediction Accuracy 56 4.3 Results 57 4.3.1 Baseline Characteristics 57 4.3.2 Cumulative Lifetime Incidence of HBsAg Seroclearance 57 4.3.3 Determinants of Spontaneous HBsAg Seroclearance 58 4.3.4 Predictors of HBsAg Seroclearance Stratified by Baseline HBV DNA Levels 58 4.3.5 Long-Term Tracking of Serum HBsAg Levels 59 4.3.6 Prediction Models for Spontaneous HBsAg Seroclearance 59 4.3.7 Discrimination and Calibration of Prediction Model 60 4.4 Discussion 61 4.5 Conclusion 64 Chapter 5: Seroclearance of HBV DNA is the Most Important Predictor for the Reduced Risk of Hepatocellular Carcinoma: A Time-Dependent Analysis of Long-Term Serially Measured Biomarkers 79 Abstract 79 5.1 Introduction 80 5.2 Methods 82 5.2.1 Study Cohort 82 5.2.2 Data Collection and Laboratory Methods 83 5.2.3 Statistical Analysis 84 5.3 Results 84 5.3.1 Baseline Characteristics 84 5.3.2 Incidence Rates and Time-Dependent Hazard Ratios of Hepatocellular Carcinoma 84 5.3.3 Hazard Ratios of Hepatocellular Carcinoma According to Disease Phase 85 5.3.4 Hazard Ratios of Hepatocellular Carcinoma Stratified by HBV DNA Level 86 5.3.5 Expanded Incidence Rates According to Various Combinations of HBV Marker Seroclearance 86 5.4 Discussion and Conclusion 88 Chapter 6: Conclusions and Future Directions 101 References 104 | |
dc.language.iso | en | |
dc.title | B型肝炎血清標幟在預測慢性B型肝炎治療效果與臨床結局的角色 | zh_TW |
dc.title | Roles of Hepatitis B Seromarkers in Predicting Treatment Endpoints and Clinical Outcomes in Chronic Hepatitis B | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-1 | |
dc.description.degree | 博士 | |
dc.contributor.coadvisor | 陳建仁(Chien-Jen Chen) | |
dc.contributor.oralexamcommittee | 楊懷壹(Hwai-I Yang),簡國龍(Kuo-Liong Chien),方啟泰(Chi-Tai Fang) | |
dc.subject.keyword | B型肝炎,表面抗原,血清標幟, | zh_TW |
dc.subject.keyword | Hepatitis B,Hepatocellular Carcinoma,HBsAg,Quantitative Surface Antigen,Seroclearance, | en |
dc.relation.page | 113 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-01-04 | |
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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ntu-101-1.pdf 目前未授權公開取用 | 2.98 MB | Adobe PDF |
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