結核病之藥物治療過程中常發生肝毒性之不良反應，而誘發肝毒性的因素除了與第一線抗結核藥物有關外，是否有其他潛在的因子可能影響抗結核藥物產生肝毒性，目前尚未有一致的定論。本研究目的在於探討病人本身疾病是否為影響發生肝毒性的相關因子。
本研究採回溯性病歷回顧自2007年1 月1日至2007年12月31日止為期一年，於南部某區域教學醫院門診或住院被首次診斷感染結核菌並接受抗結核藥物治療之病人，記錄其基本資料、疾病史、社交史、肝功能生化檢驗值等各項資料，並分析發生肝毒性的案例與其相關疾病因子是否具關聯性。
研究結果顯示，符合條件病人共228人，肝毒性發生率為61.0％（139人），高血壓與肝毒性的發生有顯著性相關（p＝0.027）。本研究發現發生肝毒性時程主要集中在服藥後第一個月發生。
因此針對在服藥後第一個月發生肝毒性與否和病人的疾病因子加以分析：發現高血壓（p＝0.008）、糖尿病（p＝0.040）與消化性潰瘍（p＝0.021）在第1個月就發生肝毒性有顯著性相關。
本研究顯示病人服用抗結核藥物發生肝毒性與病人高血壓疾病因子有顯著性相關。若以肝毒性是否在第一個月發生，則和高血壓或糖尿病或消化性潰瘍的病人有顯著性相關。因此建議在首次服用抗結核藥物時，須密切注意患有高血壓或糖尿病或消化性潰瘍的病人在第一個月產生肝毒性的情形。

Hepatotoxicity is an adverse reaction commonly observed during antituberculosis drug treatment. It is well known that the use of first-line antituberculosis drugs can induce hepatotoxicity; however, other potential factors for antituberculosis drug-induced hepatotoxicity have not yet come to a consistent conclusion. The study aimed to assess the role of comorbidity as a risk factor for the development of hepatotoxicity in patients with active tuberculosis receiving antituberculosis drug treatment.
This is an one-year retrospective study from January 1, 2007 to December 31, 2007 reviewing the medical charts of outpatients and inpatients with newly diagnosed tuberculosis and received treatment of antituberculosis drugs in a regional teaching hospital. The patient’s basic information, disease history, social history and liver function test results were recorded and analyzed for the correlation between the occurrence of hepatotoxicity and related underlying disease factors in these patients.
The results of the study have shown that a total of 228 patients met the study criteria and that the incidence of hepatotoxicity in these patients is 61.0% (139 patients). Hypertension (p=0.027) is found to be significantly associated with the occurrence of hepatotoxicity. This study demonstrated that hepatotoxicity occurred mainly within the first month of antituberculosis drug treatment. When the correlation of hepatotoxicity developed in the first month of antituberculosis drug treatment and the disease factors of patients were evaluated, it was observed that hypertension (p=0.008), diabetes (p=0.040) and peptic ulcers (p=0.021) were significantly correlated with development of hepatotoxicity in the first month of antituberculosis drug treatment.
The study has shown that development of hepatotoxicity is significantly associated in patients with hypertension, diabetes or peptic ulcer, within the first month of antituberculosis drug treatment.
It is therefore recommended that in the treatment-naive patients with underlying diseases such as hypertension, diabetes or peptic ulcer should be closely monitored for development of hepatotoxicity particularly during the first month of drug therapy.

目錄 i
表目錄 v
圖目錄 vii
誌謝 viii
中文摘要 ix
ABSTRACT xi
第一章 緒論 1
第二章 文獻探討 3
第一節 結核病流行病學 3
一、全球結核病流行趨勢 3
二、台灣結核病流行趨勢 4
第二節 結核病的特性與治療原則 6
一、特性 6
二、結核病的治療原則 6
第三節 藥物引起的肝毒性 9
一、肝毒性的定義與致病機轉 9
二、肝毒性的分類 11
第四節 抗結核藥物引起的肝毒性 13
一、第一線抗結核藥物致肝毒性之各論 13
第五節 影響抗結核藥物致肝毒性之危險因子 22
一、年齡（age） 22
二、性別（sex） 22
三、慢性病毒性肝炎感染（chronic viral hepatitis infection） 23
四、HIV感染（HIV infection） 24
五、共病（comorbidity） 25
六、白蛋白過低（hypoalbuminemia） 25
七、飲酒（alcohol consumption） 26
八、藥物乙醯化表現型（acetylator phenotype） 26
第三章 研究目的 28
第四章 研究方法 29
第一節 研究設計 29
第二節 研究對象 31
一、納入條件 31
二、排除條件 31
第三節 資料收集 33
一、病人基本資料 33
二、疾病史 33
三、社交史 34
四、用藥紀錄 34
五、肝功能生化檢驗值 34
六、其他生化檢驗值 35
第四節 資料統計與分析 36
第五節 肝毒性判定與評估標準 37
一、藥物引起肝毒性的判定標準 37
二、藥物引起肝毒性的評估標準 38
第五章 研究結果 39
第一節 研究對象基本資料分析 39
一、研究對象之納入情形 39
二、病人結核病相關診斷與肝毒性發生分布分析 42
第二節 肝毒性發生類型與發生率分析 43
第三節 發生肝毒性之危險因子分析 45
一、發生肝毒性與疾病因子分析 45
二、肝毒性發生時程與疾病因子分析 47
三、發生肝毒性之年齡層分析 49
第四節 病人共病數與發生肝毒性之關聯性 51
第六章 討論 53
第一節 樣本篩選 53
第二節 肝毒性的發生率 54
第三節 肝毒性發生與疾病因子關聯性 56
第四節 肝毒性發生與共病 57
第五節 肝毒性發生與年齡 58
第六節 研究限制 59
第七章 結論 60
第八章 參考文獻 62
附錄 70
附錄一 結核菌感染病人資料收集表 70
附錄二 人體試驗委員會同意臨床試驗證明書 72

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