目的：
本研究針對接受切除手術之慢性B型肝炎患者，評估血清檢驗法BioFibroScore的準確性，並探討在降低腫瘤因子的影響下，病理因子與病毒因子對患者預後情形的影響。
方法：
使用保存於國家衛生研究院台灣肝癌網(Taiwan liver cancer network)既有之血清檢體，收案對象為在2005-2015年間接受切除手術的慢性B型肝炎合併肝細胞癌患者，並持續追蹤其預後情形至2017年10月。本研究依據患者病理纖維化嚴重程度挑選出輕度纖維化(F0-F1)、中度纖維化(F2)及重度纖維化與肝硬化(F3-F4)各50人，透過普生股份有限公司對患者血清檢體進行Biofbroscore與Pre-S基因突變檢驗，並進一步分析檢驗結果和各項預後因子與患者預後情形間的關聯性。
結果：
本研究共收案150例患者，BioFibroScore用於慢性B型肝炎患者總體正確率僅有38%，在檢驗患者是否為肝硬化(F4)上，其陰性檢驗值為96.9%；是否為嚴重纖維化與肝硬化(F3-F4)上，其陰性檢驗值則為76.2%。Pre-S基因突變共25例(16.7%)，結果顯示Pre-S的突變情形與年齡小於50歲、多個腫瘤數、BioFibroScore檢驗結果為F3-4及HBV DNA數量>20000 IU/ml者呈正相關。在預後因素的探討中，影響患者腫瘤復發的顯著因素仍是接受切除手術前的腫瘤數量與腫瘤大小；而影響患者死亡危險因素為接受切除手術前的腫瘤數量及有血管侵犯情形。
結論：
BioFibroScore檢測在慢性B型肝炎合併肝細胞癌患者上可以有效預測非肝硬化與非嚴重纖維化，然而準確性並未達到病理組織切片的水準。在臨床運用上，Pre-S基因突變檢測依據本研究結果，可著重檢測年齡小於五十歲並且HBV DNA 病毒量> 20000 IU/ml的患者。在預後因子方面，既使鎖定腫瘤切除之患者，影響其預後情形的因素仍就以術前的腫瘤狀態為主，病理因素與病毒因素中僅有纖維化嚴重程度與兩年後腫瘤復發患者的預後相關。

Objective:
This study aims to evaluate the diagnostic accuracy of BioFibroScore in patients with chronic Hepatitis B (CHB) and hepatocellular carcinoma (HCC), and to explore the prognostic influence of pathological factors and viral factors in patients underwent curative hepatic resection for HCC.
Method:
The serum samples of this study were collected from the Taiwan liver cancer network of the National Health Research Institutes, targeting HCC in CHB Patients who underwent resection surgery between 2005 and 2015, with follow-up to October 2017.
Patients were chosen based on the severity of the fibrosis, 50 patients were selected for each of mild fibrosis (F0-F1), moderate fibrosis (F2), severe fibrosis and cirrhosis (F3-F4). BioFibroScore and Pre-S mutation tests of patients' serum samples were performed by General Biologicals Corporation. Cox regression was used to analyze the relationship between prognostic factors and patients' outcome.
Results:
A total of 150 patients were enrolled in this study. The overall accuracy of BioFibroScore in patients with chronic hepatitis B is only 38%. In testing whether the patient has cirrhosis (F4), the negative predictive value of BioFibroScore is 96.9%; in testing whether the patient has severe fibrosis or cirrhosis (F3-F4), the negative predictive value of BioFibroScore is 76.2%. There were 25 cases (16.7%) of Pre-S deletion in this study, the results showed that patients less than 50 years old, with multiple tumors before resection, the test result of BioFibroScore is F3-F4 and HBV DNA load > 20000 IU/ml are more likely to have Pre-S deletion. In the aspect of prognostic factors, the significant factors of tumor recurrence are the number of tumors and tumor size before the resection; the risk factors of the patient's death are the number of tumors before the resection and the presence of vascular invasion.
Conclusion:
The BioFibroScore test can effectively predict non-cirrhosis and non-severe fibrosis of HCC in CHB patients, but the diagnostic accuracy does not reach the level of liver biopsy. In the clinical application, the Pre-s deletion could be used to detect patient younger than 50 years old and HBV DNA viral load> 20000 IU/ml based on the results of this study. In terms of prognostic factors, even targeting patients with curative hepatic resection, tumor factors remain the most influential factor, only the severity of fibrosis relates to the prognosis of patients in the non-early recurrence group.

目錄
論文審定書 i
中文摘要 ii
Abstract iv
目錄 vi
圖目錄 viii
表目錄 ix
第一章 緒論 1
第一節 研究背景與動機 1
第二節 研究目的 2
第二章 文獻探討 3
第一節 肝癌總論 3
第二節 影響慢性B型肝炎合併肝癌患者切除手術後的預後因子 7
第三節 現有的肝纖維化檢測方式 13
第四節 小結 15
第三章 研究方法 16
第一節 研究架構與研究假設 16
第二節 資料來源與研究對象 19
第三節 研究變項與操作型定義 21
第四節 資料處理與統計分析方法 23
第四章 研究結果 24
第一節 研究對象之基本資料分析 24
第二節 BioFibroScore檢驗結果準確性分析 36
第三節 Pre-S基因突變項關性之多變項分析 38
第四節 腫瘤復發危險因素之相關性分析 42
第五節患者死亡危險因素之相關性分析 53
第五章 討論、結論與建議 56
第一節 研究假說驗證 56
第二節 研究討論 58
第三節 研究限制與建議 60
第四節 研究貢獻 61
參考文獻 62

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