臺灣博碩士論文加值系統

背景：
C型肝炎病毒是全世界肝癌的主要原因。2009年之後，台灣B型肝炎病毒和C型肝炎病毒感染相關之肝癌的比例非常接近。過去研究大多數關注於B型肝炎病毒，因此收集更多關於台灣C型肝炎相關肝癌的隱藏因素與肝癌監測有其必要。定期肝癌監測可以發現早期的腫瘤，肝癌存活率的增加主要歸因於早期發現和改善的治療方式，然而只有少數C型肝炎肝硬化患者接受了半年一次的肝癌監測。以前的研究雖確定了C型肝炎延遲診斷的一些危險因子，然而C型肝炎診斷的遺漏診斷或隱藏因素仍然存在，必須有更進一步研究來進行瞭解。特別值得一提的是，老齡化人口的增加和慢性病治療的新方法，長期增加了慢性病患者的數量，這似乎隱藏著未被發現的危險因素。另一方面，以往亞洲肝癌相關研究中，大多針對C型肝炎階段進行分析，研究肝硬化病患定期接受監測行為的研究相對較少。
目的：
因此，我們旨在探討C型肝炎延遲診斷的危險因子，並進一步探討影響C型肝炎相關之肝硬化患者不遵守定期肝癌監測的因素。最後，我們將評估肝癌監測間隔對早期肝癌診斷的影響。
方法：
在第一項研究中，我們進行了基於人口病例對照的研究。我們使用台灣健康保險2008年至2018年資料庫。將2012年至2018年間診斷出患有肝癌的患者全部納入。C型肝炎延遲診斷組包括那些在C型肝炎診斷後3年內診斷為肝癌的患者。對照組定義為自索引日期起診斷超過3年的患者。多變量邏輯模型用於找出與C型肝炎延遲診斷相關的個人和醫療提供者的相關影響因子。在第二項研究中，2003年至 2012年間，納入了新診斷為C型肝炎肝硬化的患者。對每位患者追蹤3年，直至2015年底。定期肝癌監測定義為在3年追蹤期內每年進行一次腹部超音波檢查和甲型胎兒白蛋白檢測。非定期監測定義為在3年期間沒有進行每年腹部超音波檢查和甲型胎兒白蛋白檢測。應用多項邏輯回歸模型來確定影響每年肝癌監測依從性或不依從性的因素。在第三項研究中，使用台灣健康保險2007年至2018年資料庫。納入2007年至2018年期間C型肝炎相關肝硬化的患者。我們將索引日期定義為肝癌診斷日期前90天。索引日期之前的腹部超音波檢查時間將患者分為4組：0至6個月組(6M組）、7至12個月組（12M組）、13至24個月組（24M組）和2年內未監測組（從未篩查組）。比值比(OR)用於分析不同監測間隔與肝癌診斷時分期之間的關聯。
結果：
在第一項研究中，2012年至2018年台灣C型肝炎延遲診斷比率有明顯的改善。在個人特質部分，男性、老年人、糖尿病患者和酒精相關疾病患者為C型肝炎延遲診斷的風險顯著較高。在醫療提供者特質部分，主要由男性醫生、內科醫生和家庭醫生提供治療的患者，其C型肝炎延遲診斷的風險顯著較低。在第二項研究中，新診斷為C型肝炎肝硬化只有 14%的患者，遵守年度肝癌監測。定期肝癌監測在隨時間有所改善。患有冠狀動脈疾病或慢性阻塞性肺疾病的肝硬化患者或合併症數量相對較多的患者，不遵守年度肝癌監測的可能性較高。與其他專科別醫師治療的患者相比，主要由內科專科醫師治療的患者，不遵守年度肝癌監測的可能性要小得多。主要接受大醫院執業醫師照護的患者，表現出不依從性的可能性要小得多。在第三項研究中結果發現，相較於2002-2007年，台灣於2008-2018年，C肝肝硬化的肝癌追蹤有明顯的改善。6M組由原來的52.4%上升至74.7%，而從未篩查組由26.0%下降至7.7%。6M組有明顯的早期肝癌的診斷率的機會。
結論：
論文結果發現，老年人、糖尿病患者和酒精相關疾病患者，是高風險會發生C型肝炎延遲診斷的情形。另外，醫療提供者的因素也有一定的影響，不應忽略。C型肝炎篩檢策略對肝癌高危險患者應該同時考慮病人及其照顧醫師的因素，以減少延遲診斷的狀況。在第二項研究中，C型肝炎肝硬化高危患者的 肝癌監測率非常低，我們的研究結果將有助於制定有效的干預措施以改善肝癌監測。 將肝癌監測有效整合到其他慢性合併症（尤其是冠狀動脈疾病或慢性阻塞性肺疾病）的常規就診中，對於增加定期肝癌監測可能至關重要。在第三項研究中，在第三項研究中結果發現，台灣C肝肝硬化的肝癌追蹤有明顯的改善。較短時間間隔的超音波肝癌追蹤有明顯的早期肝癌的診斷率。

The study findings suggest that the elderly, diabetic patients and patients with alcohol-related diseases were high risk groups of late HCV diagnosis. More importantly, in addition to patient characteristics, healthcare provider factors also play a significant role. HCV screening strategies should take both patient and provider factors into consideration in patients at high risk of HCC to reduce late HCV diagnosis and increase chances of early treatments or interventions. In the second study, HCC surveillance rate is very low in high-risk patients with HCV cirrhosis. For patients with more comorbidities, especially CAD or COPD, shall be the groups of patients needing special attentions and more integrated chronic care management models may be needed to increase their adherence to HCC surveillance. Effective integration of HCC surveillance into routine visits for other chronic comorbidities, especially CAD or COPD, may be critical to increase HCC surveillance. In the third study, we found a significant improvement in HCC surveillance in patients with -related cirrhosis in Taiwan over time. A 6-month ultrasonography screening interval yields the highest likelihood of diagnosing early HCC among patients with HCV-related cirrhosis.

中文摘要................................................................................................................... i
Abstract ............................................................................................................ iv
Table of contents ....................................................................................................... viii
List of Figures ............................................................................................................ x
List of Tables ............................................................................................................. xi
CHAPTER ONE: INTRODUCTION ...................................................................... 1
I Background .................................................................................................... 1
II Specific Aim ................................................................................................. 4
CHAPTER TWO: LITERATURE REVIEW .......................................................... 5
I Late Diagnosis of Hepatitis C Virus Infection and Its Influencing Factors….5
II Factors associated with nonadherence to surveillance for hepatocellular carcinoma among patients with hepatic C virus cirrhosis…………………….10
III Surveillance interval and its influence on early hepatocellular carcinoma diagnosis in cirrhotic patients with hepatitis C virus infection………………..16
IV: Summary of Gap in Literatures................................................................. 20
CHAPTER THREE: METHODS ........................................................................... 22
I National Health Insurance Research Database ............................................. 22
II Study Sample ............................................................................................... 23
III Construction of Variables .......................................................................... 24
IV Statistical Analyses………………………………………………………...26
CHAPTER FOUR: Late Hepatitis C Virus Diagnosis Among Patients with Newly Diagnosed Hepatocellular Carcinoma: A Case-Control Study................................ 27
I Abstract ........................................................................................................ 27
II Introduction ................................................................................................ 28
III Methods..................................................................................................... 30
IV Results ...................................................................................................... 34
V Discussion ................................................................................................. 42
CHAPTER FIVE: Factors associated with nonadherence to surveillance for hepatocellular carcinoma among patients with hepatic C virus cirrhosis, 2000-2015. ...................................................................................................................... 47
I Abstract ....................................................................................................... 47
II Introduction ............................................................................................... 49
III Methods.................................................................................................... 51
IV Results ..................................................................................................... 57
V Discussion ................................................................................................ 63
CHAPTER SEX: The influence of surveillance interval on early-stage hepatocellular carcinoma diagnosis in cirrhotic patients with hepatitis C virus infection…….…68
I Abstract ....................................................................................................... 68
II Introduction ............................................................................................... 70
III Methods..................................................................................................... 72
IV Results ...................................................................................................... 76
V Discussion ................................................................................................. 78
CHAPTER SEVEN: CONCLUSION ................................................................... 87
I Summary of Significant Findings ............................................................... 87
II Study Strength and Limitation ................................................................... 88
III Policy Implication .................................................................................... 89
REFERENCES ...................................................................................................... 91

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