感染不同B型肝炎病毒基因型及突變株對血清中B型肝炎病毒表面抗原濃度之相關性研究

Hepatitis B Virus Genotype and Mutants associated with the Expression of Hepatitis B Surface Antigen in Serum

游凱翔(Kai-Hsiang You)

指導教授 ： 陳建仁 ； 蕭朱杏

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.10936

摘要

背景及目標：近年來血清中HBsAg濃度可反應慢性B型肝炎患者的疾病自然史及預測抗病毒藥物治療反應。血清中HBsAg的產生可能會受到病毒與宿主間交互作用影響，到目前為止，HBV的基因型及突變株對於HBsAg濃度的影響仍不太清楚。本研究主要評估HBV的基因型、前核心區及基礎核心促進子之突變對於HBsAg濃度的影響。方法：資料來自1991年到1992年間收集的社區世代研究，共計2,312名無肝癌既往史之個案參加。在基線收集個案的血液，基因型測定是利用melting curve analysis，而使用羅氏Elecsys HBsAg II Quant assay定量HBsAg濃度。另外共計1,440名個案血清中HBV DNA濃度大於104 copies/mL，利用direct sequencing測量前核心區及基礎核心促進子之突變。利用線性回歸或羅吉斯回歸再調整相關干擾因素後，找出影響血清中HBsAg濃度因素。結果：在個案血清中HBV DNA濃度大於104 copies/mL為研究對象的多變量迴歸分析中，基因型C相較於基因型B有較高的HBsAg濃度(β=0.43, SE=0.04, p<0.0001)；前核心區的Mutant type相較於Wild type有較低的HBsAg濃度(β=-0.26, SE=0.05, p<0.0001)；基礎核心促進子的mutant type相較於wild type有較低的HBsAg濃度(β=-0.22, SE=0.05, p<0.0001)。而基因型C相較於基因型B在兩組dataset都與較高的HBsAg濃度有關。在結合了基因型、前核心區及基礎核心促進子，結果發現，當基因型C、前核心區及基礎核心促進子為Wild type相較於基因型B、前核心區及基礎核心促進子為Wild type有較高的HBsAg濃度(β=0.65, SE=0.11, p<0.0001)。結論：HBV的基因型、前核心區及基礎核心促進子的突變與HBsAg濃度有關，基因型C對於血清中HBsAg濃度是高於基因型B，而前核心區及基礎核心促進子的Mutant type對於血清中HBsAg濃度是低於Wild type。

關鍵字

B型肝炎病毒 ； B型肝炎病毒表面抗原 ； 基因型 ； 突變株 ； 前核心區 ； 基礎核心促進子

並列摘要

Background & Aims: Qualitative Hepatitis B surface antigen (HBsAg) is becoming an innovative concept that information on HBsAg levels can address the natural history of the disease and predict treatment response in chronic hepatitis B (CHB). The production of HBsAg may change during the virus-host interaction in CHB. The impact of HBV genotype and hotspot mutants on HBsAg production remains unclear. This study aimed to evaluate the effects of HBV genotype and precore and basal core promoter mutations on the expression of HBsAg. Methods: A total of 2,312 individuals with CHB infection were enrolled between 1991 and 1992 in this community-based study. Serum samples collected at baseline were tested for genotype by melting curve analysis and HBsAg levels at study entry were quantified using the Roche Elecsys HBsAg II Quant assay. Participants who had a baseline serum HBV DNA level greater than 104 copies/mL (n=1,440) were tested for precore G1896A and BCP A1762T/G1764A mutants by direct sequencing. Multiple regression analyses were performed to identify the independent factors affecting serum HBsAg titers. Results: Among participants with a baseline HBV DNA level of 104 copies/mL or greater, the multivariable-adjusted beta coefficient of the expression of HBsAg was 0.43 (SE=0.06) for genotype C versus genotype B, -0.26 (SE-0.05) for precore mutant type versus wild type, -0.22 (SE=0.05) for BCP mutant type versus wild type. as associated with a higher HBsAg expression than infection with genotype B for both dataset analyses. HBsAg titers were lowest among participants infected with genotype C HBV and mutant type for precore 1896 variant and mutant type for the BCP 1762/1764 variant (beta coefficient=-0.75, SE-0.08, p<0.0001). Conclusions: HBV genotype and precore and BCP mutants are correlated with the expression of HBsAg titers. Effect of genotype C on the expression of HBsAg was higher than genotype B and effects of precore and BCP mutants on the expression of HBsAg were lower than wild type.

並列關鍵字

Hepatitis B Virus ； Hepatitis B Surface Antigen ； HBV Genotype ； HBV Mutants ； Precore ； Basal Core Promoter

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