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

Roles of Hepatitis B Seromarkers in Predicting Treatment Endpoints and Clinical Outcomes in Chronic Hepatitis B

劉薇真(Jessica Liu)

指導教授 ： 蕭朱杏

共同指導教授 ： 陳建仁(Chien-Jen Chen)

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/博士(2012年)

https://doi.org/10.6342/NTU.2012.00150

摘要

無資料

關鍵字

B型肝炎 ； 表面抗原 ； 血清標幟

並列摘要

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.

並列關鍵字

Hepatitis B ； Hepatocellular Carcinoma ； HBsAg ； Quantitative Surface Antigen ； Seroclearance

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