抗結核藥物產生肝毒性與病人相關因子之研究

Correlation between Antituberculosis Drug-Induced Hepatotoxicity and Patient-Related Factors

楊璦瑜(Ai-Yu Yang)

指導教授 ： 溫燕霞

高雄醫學大學/藥學院/藥學系碩士在職專班/碩士(2015年)

摘要

結核病目前在台灣仍是最嚴重的傳染病之一，治療用藥常見有肝毒性產生。本研究目的在探討使用抗結核用藥產生肝毒性與病人相關因子的關聯性。
採回溯性病歷回顧自2008年10月至2011年9月共三年，在南部某醫學中心門診或住院首次診斷為結核病並接受抗結核藥物治療的病人。記錄病人基本資料、社交史、抗結核用藥療程、肝功能相關檢驗數值、共病、共病藥物。分析使用抗結核藥物產生肝毒性與病人性別、年齡、個人史、疾病史、共病藥物的相關性；次分析肝毒性發生時程、肝毒性嚴重度與病人共病、共病藥物的相關性。
研究納入1192人，符合收案條件共641人，治療期間產生肝毒性共122人（19.0％）。發生肝毒性以男性（80人，66％）、70歲以上（50％）佔多數。病人使用抗結核用藥發生肝毒性與慢性肝炎、高血壓、癌症、攝護腺肥大有顯著相關（P＜0.05）；與併服的共病藥物：糖尿病用藥metformin、胃腸道潰瘍用藥cimetidine、esomeprazole、高血脂用藥rosuvastatin也有相關性（P＜0.05）。
綜合比較整體肝毒性發生率、肝毒性好發時程、嚴重肝毒性，只有癌症皆呈現顯著相關性（P＜0.05），為共病風險因子。另外cimetidine造成嚴重肝毒性的風險是沒有使用者的6倍。共病數越多，使用抗結核藥產生肝毒性的風險越高（P＜0.05）。
考量台灣步入高齡化社會，共病數與使用共病藥物增加。建議使用抗結核藥物治療的病人須同時注意共病及共病藥物，兩者分別皆有可能是影響肝毒性發生的獨立風險因子。

關鍵字

抗結核藥物 ； 肝毒性 ； 共病 ； 共病藥物

並列摘要

Tuberculosis has been one of the most serious infectious diseases in Taiwan. The using of the anti-tuberculosis drugs often induces with the hepatotoxicity. In this study, we investigated the patients using anti-tuberculosis drugs which come to produce the hepatotoxicity that correlated with patients’s comorbidity and their medications for certain comorbidities
Taking a retrospective study, we had studied patients from October 2008 to September 2011 in a southern medical center. We had reviewed the medical charts of outpatient and inpatient with newly diagnosed tuberculosis and received treatment of anti-tuberculosis drugs. In the study, basic patient information, past disease history, personal history, anti-tuberculosis drug treatment regimen, liver function test values, and medications for comorbidity had been recorded. Furthermore, our study also had analyzed for the correlation of using anti-tuberculosis drugs which induce in hepatotoxicity that related with patients’s sex, age, social history, past disease history, and medications for comorbidity.
Our study included 1,192 persons, 641 cases met the inclusion criteria and 122 persons (19.0%) during treatment had hepatotoxicity. Chronic hepatitis, hypertension, cancer, and benign prostatic hyperplasia, patients’s comorbidities, were significantly correlated with the occurrence of hepatotoxicity (P <0.05). Metformin, cimetidine, esomeprazole, and rosuvastatin, medications for comorbidity, had significant correlation with the occurrence of hepatotoxicity (P <0.05).
Comparison to three aspects of hepatotoxicity(incidence of hepatotoxicity, the time of hepatotoxicity predilection, severe hepatotoxicity), only cancer had a significant risk factor for hepatotoxicity (P＜0.05). In addition, using cimetidine to occur in severe hepatotoxicity was 6-times than no using cimetidine. Larger number of comorbidities in patient had a higher risk of hepatotoxicity.
Entering the aging society in Taiwan, number of comorbidities and medications for comorbidity in patients will increase. The patients who take the anti-tuberculosis drugs treatment are highly recommend to watch out patients’s comorbidities and their medications for comorbidities. Comorbidity and medications for comorbidity both maybe are the risk factors which can individually affect the occurrence of hepatotoxicity in tuberculosis patient.

並列關鍵字

antituberculosis drugs ； hepatotoxicity ； comorbidities ； medications for comorbidity

參考文獻

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