臺灣博碩士論文加值系統

目的：本研究的目的在於探討2003年後法令允許使用唯一馬兜鈴科中藥細辛，其臺灣中醫師處方的適應症、頻率、處方形態，以及與肝癌發生風險的相關性。
方法：本研究利用全民健康保險資料庫百萬歸人檔，進行對非B型/非C型肝炎世代族群、B型肝炎世代族群及C型肝炎世代族群，排除2005年以前使用過含馬兜鈴酸的中藥族群，針對2005至2013年間使用細辛的族群進行分析，釐清當細辛於非B型肝炎、非C型肝炎病患族群，或者與B型肝炎、C型肝炎的協同作用，是否會上升肝癌的發生風險。
結果：臺灣中醫師處方馬兜鈴科中藥細辛的適應症，最常出現的為呼吸系統疾病，佔32.3%；開立總天數最多的為川芎茶調散，佔19.3%，平均每天開立4.3g。將細辛使用者與非中藥使用者配對性別、年齡、慢性肝病等潛在干擾因素後，依細辛暴露的累積劑量分層分析，於非B型肝炎/非C型肝炎族群的細辛使用者，相較於未曾使用過中醫的族群，在細辛累積1-30g時HR：0.34(95%CI：0.20-0.57)、31-60g HR：0.20(95%CI：0.05-0.82)、61-100g HR：0.42(95%CI：0.10-1.71)、101-200g HR：0.20(95%CI：0.03-1.45)；細辛與B型肝炎協同作用時1-30g HR：0.32(95%CI：0.18-0.58)、31-60g HR：0.23(95%CI：0.06-0.95)、61-100g HR：0.20(95%CI：0.03-1.48)；細辛與C型肝炎協同作用時1-30g時HR：0.38(95%CI：0.18-0.79)、31-60g HR：0.52(95%CI：0.16-1.71)、61-100g HR：0.29(95%CI：0.04-2.15)、大於201g HR：1.57(95%CI：0.37-6.59)，結果顯示三組都沒有上升肝癌發生風險。
結論：法規規範後臺灣中醫師處方治療呼吸道疾病仍非常頻繁處方馬兜鈴科中藥細辛，本研究顯示細辛不會上升肝癌發生風險；細辛與B型肝炎、C型肝炎病毒並沒有協同上升肝癌發生的作用。

Background: The aim of this study is to investigate the remaining genus aristolochia, Asari Radix or xixin, and its prescription pattern and the risk to hepatocellular carcinoma (HCC) after health regulations in 2003.
Methods: We used million NHIRD database to investigate the risk of xixin and HCC in hepatitis B virus (HBV) infected, hepatitis C virus (HCV) infected and non-HBV/ non-HCV infected corhorts between 2005 and 2013.
Results: Respiratory disorders are most common in xixin prescriptions pattern and Chuan Xiong Cha Tiao San has highest prescricriptions, with an average daily dosage of 4.3g. After adjustment of age, gender and hepetatis conditions, xixin alone has HR: 0.34(95%CI：0.20-0.57) in 1-30g、HR: 0.20(95%CI：0.05-0.82) in 31-60g、HR: 0.42(95%CI：0.10-1.71) in 61-100g and HR: 0.20(95%CI：0.03-1.45) in 101-200g as compared to non-Traditional Chinese Medicine (TCM) users; xixin interacts with HBV has HR：0.32(95%CI：0.18-0.58) in 1-30g、HR：0.23(95%CI：0.06-0.95) in 31-60g and HR：0.20(95%CI：0.03-1.48) in 61-100g as compared to non-TCM users; xixin interacts with HCV has HR:0.38(95%CI：0.18-0.79) in 1-30g、HR:0.52(95%CI：0.16-1.71) in 31-60g and HR:0.29(95%CI：0.04-2.15) in 61-100g and HR:1.57(95%CI：0.37-6.59) over 200g as compared to non-TCM users. All failed to increased the risk of HCC.
Conclusions: Asari Radix (Xixin) is very frequenctly used to treat repiratory diseases nowadays. This study shows that xixin dose not increase the risk of HCC, even is alone or synergistically with HBV or HCV.

目錄
第一章 前言 1
第一節 研究背景 1
第二節 研究目的 3
第二章 文獻探討 4
第一節 探討導致肝癌的危險因子 4
第二節 攝食含中草藥馬兜鈴酸與DNA adduct 的關係 11
第三節 攝食含馬兜鈴酸所引起的肝病變 13
第四節 中草藥馬兜鈴科植物細辛 17
第三章 材料與方法 19
第一節 全民健康保險資料庫探查2005年以後，臺灣中醫師處方馬兜鈴科中藥 (細辛)的適應症、頻率、處方形態。 19
(一)、 患者的篩選 19
(二)、 統計分析 20
第二節 全民健康保險資料庫探查非B型/非C型肝炎世代，處方細辛與肝癌的相關性研究 21
(一)、 細辛使用者的定義 22
(二)、 肝癌使用者定義 23
(三)、 社會與經濟變項 23
(四)、 共病症 24
(五)、 用藥 25
(六)、 中藥使用 25
(七)、 配對方法 25
(八)、 研究終點及追蹤時間 26
(九)、 統計方法 26
第三節 全民健康保險資料庫探查B型肝炎世代，處方細辛與肝癌的相關性研究 27
(一)、 細辛使用者的定義 28
(二)、 肝癌使用者定義 29
(三)、 社會與經濟變項 29
(四)、 共病症 30
(五)、 用藥 31
(六)、 中藥使用 31
(七)、 配對方法 32
(八)、 研究終點及追蹤時間 32
(九)、 統計方法 32
第四節 全民健康保險資料庫探查C型肝炎世代，處方細辛與肝癌的相關性研究 33
(一)、 細辛使用者的定義 34
(二)、 肝癌使用者定義 35
(三)、 社會與經濟變項 35
(四)、 共病症 36
(五)、 用藥 37
(六)、 中藥使用 37
(七)、 配對方法 38
(八)、 研究終點及追蹤時間 38
(九)、 統計方法 38
第四章 結果 39
第一節 全民健康保險資料庫探查2005年以後，臺灣中醫師處方馬兜鈴科中藥 (細辛)的適應症、頻率、處方形態。 39
第二節 全民健康保險資料庫探查非B型/非C型肝炎世代，處方細辛與肝癌的相關性研究 40
第三節 全民健康保險資料庫探查B型肝炎世代，處方細辛與肝癌的相關性研究 44
第四節 全民健康保險資料庫探查C型肝炎世代，處方細辛與肝癌的相關性研究 48
第五章 討論 52
第六章 結論 56
參考文獻 57
附錄 69
附件 1、從臺灣肝癌發現高比例帶有馬兜鈴酸特有的基因突變特徵研究的新聞事件：談醫療人員如何正確宣揚研究成果 （TJ TCM.21(1) : 97-110, 2018） 94
附件 2、從臺灣肝癌發現高比例帶有馬兜鈴酸特有的基因突變特徵研究的新聞事件：以流行病學觀點評述 （投稿中） 94


圖目錄
圖 一：同時性(synchronous)及異時性(metachronous)癌症發生的時間點 9
圖 二：非B型/非C型肝炎世代族群篩選流程圖 76
圖 三：B型肝炎世代族群篩選流程圖 82
圖 四：C型肝炎世代族群篩選流程圖 88



表目錄
表 一：比利時個案追蹤AA-adducts與服用AA I劑量的關係圖 69
表 二：動物實驗AA-adducts與服用AA I劑量的關係圖 70
表 三：研究中所使用的疾病ICD-9代碼 71
表 四：2005-2013年所有細辛使用之適應症、頻率 73
表 五：2005-2013年中醫師最常開立含細辛的單方及方劑 74
表 六：非B型/非C型肝炎研究族群與配對結果 77
表 七：非B型/非C型肝炎中處方細辛對於肝癌的校正風險比 79
表 八：B型肝炎研究族群與配對結果 83
表 九：B型肝炎中處方細辛對於肝癌的校正風險比 85
表 十：C型肝炎研究族群與配對結果 89
表 十一：C型肝炎中處方細辛對於肝癌的校正風險比 91

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