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研究生(外文):Chi-Hsien Ho
論文名稱(外文):Development of a Risk Score for Predicting Hepatotoxicity during HMG-CoA Reductase Inhibitors Therapy in Diabetic Patients
外文關鍵詞:HMG-CoA Reductase InhibitorsHepatotoxicityRisk Score
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HMG-CoA還原酶抑制劑 (3-hydroxy-3-methyl-gutaryl-CoA reductase inhibitors, statins) 引起的肝毒性雖常見,但多數病人肝功能指數會自發性回復正常,因此臨床上糖尿病人使用時監測情形並不如藥品仿單建議的頻繁。但若嚴重肝毒性發生,就可能會降低病人的服藥配合度,甚至損害健康。糖尿病盛行率逐年增加,估計其中約有50%患者會同時併有血脂異常,因此常需併用statins治療。除了高血脂,肝臟疾病也是一個重要卻常被忽略的糖尿病合併症。在糖尿病病人接受statins治療時,應要有符合臨床需要和經濟效應的肝功能監測建議,以有效的進行肝功能檢測,並避免肝臟相關不良反應導致服藥依順性低而造成浪費。
本研究目的為利用糖尿病患者在statins 治療期間發生肝毒性的危險因子,建立一套預測量表,以輔助肝功能監測的安排。收案地點為台北醫學大學-市立萬芳醫院,共回溯219名糖尿病患之病歷,收集資料包括病人基本資料與合併疾病、生化檢驗數據,與使用藥物品項與劑量等。以univariate analysis評估潛在危險因子與statins使用期間發生的肝毒性之相關性。具有統計意義的危險因子再以logistic regression進行分析,並以危險因子進行配分,建立statins使用期間發生肝毒性的預測量表。量表之配適度以Hosmer-Lemeshow test評估,其檢測力則以receiver-operating characteristic (ROC) curve 下的面積(AUC)、sensitivity與specificity示之。
經過logistic regression分析並建立的量表總共包括五項危險因子:(1)男性,(2)三酸甘油脂的檢驗基準值,(3)糖尿病罹病期間,(4)合併疾病數,以及(5)病患所使用的angiotensin-converting enzyme inhibitors (ACEI)之每日處方劑量(Prescribed Daily Dose, PDD) 與每日定義劑量(Defined Daily Dose,DDD) 的比率。ROC 曲線下面積為0.864,Hosmer-Lemeshow test 的p 值為0.674,所得預測量最佳切點(cutoff point)為4.5分。大於50%以上的肝毒性發生在statins使用後半年內,因此建議STH預測量表得分大於4.5分的糖尿病患,應在statins開始使用的第三個月、第六個月、第十二個月,與第十八個月進行肝功能監測。
HMG-CoA reductase inhibitors (statins)-induced hepatotoxicity is a common adverse effect characterized by asymptomatic and transient elevations in liver enzymes. Due to the self-resolving nature, even without statin discontinuation, the frequency of monitoring of liver function tests (LFT) in patients receiving statin therapy is usually lower than the manifacturers’ recommendations. Although hepatotoxicity is rarely severe, once it occurs, patients are endangered directly by the event itself and indirectly from lowered patient compliance. Hyperlipidemia and liver diseases are important diabetic comorbidities. While statin is the most commonly prescribed lipid lowering agent, its hepatotoxicity in diabetic hyperlipidemic patients requires further evaluation. Current LFT monitoring recommendations should adjust to accommodate the clinical needs of diabetic patients during statins therapy.
This retrospective analysis was conducted to determine factors associated with hepatotoxicity among diabetic patients during statins therapy and to develop a risk score. Data of 219 patients were collected from the medical charts of Municipal Wan-Fang Hospital. Potential risk factors were assessed by univariate analysis for their association with hepatotoxicity during statin therapy. Factors significantly associated with the outcome were further evaluated in logistic regression analysis. A risk model was constructed by regression coefficients. Hosmer-Lemeshow test was performed to evaluate model fit. Discriminatory power was determined by area under receiver-operating characteristic curve (ROC curve).
Five risk factors were found significantly associated with hepatotoxicity during statin therapy and were incorporated to construct a risk model predicting hepatotoxicity. These factors included: (1) male gender, (2) baseline triglyceride level, (3) years since diabetes diagnosis, (4) number of diagnoses, and (5) PDD/DDD (Prescribed Daily Dose/Defined Daily Dose) ratio of angiotensin converting enzyme inhibitors. Area under ROC curve was 0.864 for the predictive model. Hosmer-Lemeshow test revealed a p-value of 0.674. Base on the findings in this study, it is advised that diabetic patients with STH score of 4.5 or above should monitor liver function at baseline, month 1, 3, 6, 9, 12, and 18 after initiation of statins.
中文摘要 3
英文摘要 4
目次 5
表目錄 7
圖目錄 9
第1章 緒論 1
第2章 文獻探討 2
2.1 HMG-COA REDUCTASE於糖尿病血脂異常之臨床用途與使用現況 2
2.1.1 糖尿病血脂異常 2
2.1.2 降血脂藥物在糖尿病合併血脂異常的治療 7
2.1.3 HMG-CoA Reducatse Inhibitors之臨床用途與使用現況 9
2.3 藥物引起之肝毒性 15
2.3.1 藥物引起肝毒性之分類與機轉 15
2.3.2 藥物引起肝毒性的危險因子 17
2.3.3 HMG-CoA Reductase抑制劑引起之肝毒性 18
2.3.4 HMG-CoA Reductase 抑制劑引起肝毒性的危險因子 18
第3章 研究目的 20
第4章 研究方法 21
4.1 研究設計 21
4.2 研究對象 22
4.2.1 本研究納入之對象 22
4.2.2 本研究之排除標準 22
4.3 資料收集 23
4.3.1 資料收集之內容 23
4.3.2 研究相關定義 24
4.4 肝毒性判定與評估 30
4.4.1 藥物引起之肝毒性分類 30
4.4.2 肝毒性與Statins相關性之評估 30
4.5 資料統計與分析 32
4.5.1 基本資料分析 32
4.5.2 肝毒性相關因子分析 32
4.5.3 預測量表建立與驗證 33
第5章 研究結果 35
5.1 研究對象初步資料分析 35
5.1.1 研究對象納入狀況 35
5.1.2 基本資料分析 35
5.1.3 糖尿病患者Statins與併用藥物使用情形 36
5.1.4 研究對象檢驗基準值 38
5.2 糖尿病患者STATINS使用期間肝毒性發生率 41
5.2.1 肝毒性發生率 41
5.2.2 肝毒性發生時間點與檢驗值 41
5.2.3 肝毒性與不良反應的相關性評估 43
5.3 肝毒性相關危險因子分析 45
5.3.1 研究對象基本資料 45
5.3.2 生化檢測基準值 47
5.3.3 Statins與併用藥物 48
5.4 預測量表的建立 52
5.5 預測量表的驗證 55
第6章 討論 63
6.1 糖尿病患在STATINS治療期間發生之肝毒性 63
6.2 肝毒性的危險因子 65
6.2.1 性別 65
6.2.2 糖尿病罹病時間 67
6.2.3 三酸甘油酯檢驗基準值 68
6.2.4 合併疾病 69
6.2.5 Statins與合併藥物 70
6.3 使用STATINS期間之肝功能監測 76
第7章 研究限制 78
第8章 結論 79
參考文獻 80
附件 87
1.潘文涵, 傅茂祖, 戴東原, 莊立民, 林宏達. 糖尿病防治手冊(糖尿病預防、診斷與控制流程指引): 行政院衛生署國民健康局; 2004.
2.Tolman KG, Fonseca V, Dalpiaz A, Tan MH. Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease. Diabetes Care 2007;30:734-43.
3.International Diabetes Federation. (Accessed June, 10, 2008, at http://www.idf.org/home/index.cfm?unode=3B96906B-C026-2FD3-87B73F80BC22682A.)
4.Brun E, Nelson RG, Bennett PH, et al. Diabetes duration and cause-specific mortality in the Verona Diabetes Study. Diabetes Care 2000;23:1119-23.
5.De Marco R, Locatelli F, Zoppini G, Verlato G, Bonora E, Muggeo M. Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study. Diabetes Care 1999;22:756-61.
6.Garg A, Grundy SM. Management of dyslipidemia in NIDDM. Diabetes Care 1990;13:153-169.
7.Chitturi S, George J. Hepatotoxicity of commonly used drugs: nonsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, psychotropic drugs. Semin Liver Dis 2002;22:169-83.
8.Cohen DE, Anania FA, Chalasani N. An assessment of statin safety by hepatologists. Am J Cardiol 2006;97:77C-81C.
9.Jacobson TA. Statin safety: lessons from new drug applications for marketed statins. Am J Cardiol 2006;97:44C-51C.
10.Rathmann W, Giani G. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:2568-9; author reply 9.
11.Cockram CS. The epidemiology of diabetes mellitus in the Asia-Pacific region. Hong Kong Med J 2000;6:43-52.
12.白其卉, 游山林, 簡國龍. 台灣地區高血壓、高血糖、高血脂之盛行率調查: 行政院衛生署國民健康局; 2003.
13.全民健康保險統計年報:前二十大死因戶籍縣市鄉鎮別就診統計-年齡五歲組別. 2006. (Accessed at http://www.doh.gov.tw/statistic/.)
14.Roper NA, Bilous RW, Kelly WF, Unwin NC, Connolly VM. Cause-specific mortality in a population with diabetes: South Tees Diabetes Mortality Study. Diabetes Care 2002;25:43-8.
15.Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-421.
16.中華民國血脂及動脈硬化學. 高血脂防治手冊國人血脂異常診療及預防指引.行政院衛生署國民健康局; 2004.
17.U.K. Prospective Diabetes Study 27. Plasma lipids and lipoproteins at diagnosis of NIDDM by age and sex. Diabetes Care 1997;20:1683-7.
18.Alexander CM, Landsman PB, Teutsch SM, Haffner SM. NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003;52:1210-4.
19.Cottrell DA, Marshall BJ, Falko JM. Therapeutic approaches to dyslipidemia in diabetes mellitus and metabolic syndrome. Curr Opin Cardiol 2003;18:301-8.
20.American Diabetes Association Clinical Practice Recommendations 2007. Diabetes Care 2007;30:13~5.
21.Grundy. Erratum: Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines (Circulation (July 13, 2004) 110 (227-239)). Circulation 2004;110:763.
22.Haffner SM. Management of dyslipidemia in adults with diabetes. Diabetes Care 2003;26 Suppl 1:S83-6.
23.Haffner SM. Dyslipidemia management in adults with diabetes. Diabetes Care 2004;27 Suppl 1:S68-71.
24.Guan J-Z, Tamasawa N, Murakami H, et al. HMG-CoA Reductase inhibitor Simvastain Improves Reverse Cholesterol TRansport in Type 2 Diabetic Patients with Hyperlipidemia. Journal of Atherosclerosis and Thrombosis 2008;15:1-5.
25.Jerwood S, Cohen J. Unexpected antimicrobial effect of statins. J Antimicrob Chemother 2008;61:362-4.
26.Jasinska M, Owczarek J, Orszulak-Michalak D. Statins: a new insight into their mechanisms of action and consequent pleiotropic effects. Pharmacol Rep 2007;59:483-99.
27.Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003;361:2005-16.
28.Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 2008;371:117-25.
29.Chiang CW, Chiu HF, Chen CY, Wu HL, Yang CY. Trends in the use of lipid-lowering drugs by outpatients with diabetes in Taiwan, 1997-2003. Pharmacoepidemiology and Drug Safety 2008;17:62-9.
30.Bolego C, Baetta R, Bellosta S, Corsini A, Paoletti R. Safety considerations for statins. Curr Opin Lipidol 2002;13:637-44.
31.Farmer JA, Torre-Amione G. Comparative tolerability of the HMG-CoA reductase inhibitors. Drug Saf 2000;23:197-213.
32.Kiortsis DN, Filippatos TD, Mikhailidis DP, Elisaf MS, Liberopoulos EN. Statin-associated adverse effects beyond muscle and liver toxicity. Atherosclerosis 2007;195:7-16.
33.Pasternak RC, Smith SC, Jr., Bairey-Merz CN, Grundy SM, Cleeman JI, Lenfant C. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins. Stroke 2002;33:2337-41.
34.Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol 2006;97:52C-60C.
35.McKenney JM, Davidson MH, Jacobson TA, Guyton JR. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006;97:89C-94C.
36.Cziraky MJ, Willey VJ, McKenney JM, et al. Statin safety: an assessment using an administrative claims database. Am J Cardiol 2006;97:61C-8C.
37.Alsheikh-Ali AA, Karas RH. Adverse events with concomitant use of simvastatin or atorvastatin and thiazolidinediones. Am J Cardiol 2004;93:1417-8, A9.
38.Bottorff M. Concomitant use of cytochrome P450 3A4 inhibitors and simvastatin. Am J Cardiol 2000;85:1042-3.
39.Bottorff MB. Statin safety and drug interactions: clinical implications. Am J Cardiol 2006;97:27C-31C.
40.Chang CY, Schiano TD. Review article: drug hepatotoxicity. Aliment Pharmacol Ther 2007;25:1135-51.
41.Davidson MH, Clark JA, Glass LM, Kanumalla A. Statin safety: an appraisal from the adverse event reporting system. Am J Cardiol 2006;97:32C-43C.
42.Russo MW, Jacobson IM. How to use statins in patients with chronic liver disease. Cleve Clin J Med 2004;71:58-62.
43.CD Holt, Arriola E. Adverse Effects of Drugs on the Liver. In: Koda-Kimble MA YL, Kradjan WA, Guglielmo BJ, Alldredge BA, Corelli RL, ed. Applied Therapeutics: The Clinical Use of Drugs. 8 ed: Lippincott Williams & Wilkins; 2004:1-25.
44.RJ Temple, Himmel MH. Safety of newly approved drugs: implications for prescribing. JAM 2002;287:2273-5.
45.Y Meier, M Cavallaro, M Roos, al e. Incidence of Drug-induced Hepatic Injuries: A French Population-Based Study. Hepatology 2005;2002:451-5.
46.MacLaren R. Hepatic and Cholestatic Disease. In: Drug-Induced Disease:515-35.
47.Bénichou C. Criteria of drug-induced liver disorders : Report of an International Consensus Meeting. Journal of Hepatology 1990;11:272-6.
48.Lee WM. Drug-induced hepatotoxicity. N Engl J Med 2003;349:474-85.
49.Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 2006;80:565-81.
50.Ghali P, Lindor KD. Hepatotoxicity of drugs used for treatment of obesity and its comorbidities. Semin Liver Dis 2004;24:389-97.
51.Bhardwaj SS, Chalasani N. Lipid-lowering agents that cause drug-induced hepatotoxicity. Clin Liver Dis 2007;11:597-613, vii.
52.Parra JL, Reddy KR. Hepatotoxicity of hypolipidemic drugs. Clin Liver Dis 2003;7:415-33.
53.Chalasani N, Aljadhey H, Kesterson J, Murray MD, Hall SD. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology 2004;126:1287-92.
54.Vuppalanchi R, Teal E, Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes. Am J Med Sci 2005;329:62-5.
55.OPDRA safety review: statins and hepatotoxicity. AERS Food and Drug Administration, 2000. (Accessed May 1, 2000., at http://www.fdagov/medwatch/safety /2000.)
56.Deambrosis P, Saramin C, Terrazzani G, et al. Evaluation of the prescription and utilization patterns of statins in an Italian local health unit during the period 1994-2003. Eur J Clin Pharmacol 2007;63:197-203.
57.WHO Collaborating Centre for Drug Statistics Methodology. (Accessed at http://www.whocc.no/atcddd/.)
58.Danan G, Benichou C. Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol 1993;46:1323-30.
59.Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.
60.Linden A. Measuring diagnostic and predictive accuracy in disease management: an introduction to receiver operating characteristic (ROC) analysis. J Eval Clin Pract 2006;12:132-9.
61.台灣地區各類法定傳染病個案報告表. 2008. (Accessed May, 2, 2008, at https://teb.cdc.gov.tw/upload/doc/21232_台灣地區各類法定傳染病個案報告表.pdf.)
62.國際疫情及新知. 2008. (Accessed May, 2, 2008, at http://teb.cdc.gov.tw:8080/CDC_KSP/readFile.)
63.Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med 1998;339:1349-57.
64.Pedersen TR, Kjekshus J, Berg K, et al. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). 1994. Atheroscler Suppl 2004;5:81-7.
65.Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996;335:1001-9.
66.Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA 2001;285:1711-8.
67.Shear CL, Franklin FA, Stinnett S, et al. Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. Effect of patient characteristics on lovastatin-induced changes in plasma concentrations of lipids and lipoproteins. Circulation 1992;85:1293-303.
68.Tonkin AM. Management of the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study after the Scandinavian Simvastatin Survival Study (4S). Am J Cardiol 1995;76:107C-12C.
69.Clark JM, Diehl AM. Hepatic steatosis and type 2 diabetes mellitus. Curr Diab Rep 2002;2:210-5.
70.Hickman IJ, Macdonald GA. Impact of diabetes on the severity of liver disease. Am J Med 2007;120:829-34.
71.Hoppin AG. Obesity and the liver: developmental perspectives. Semin Liver Dis 2004;24:381-7.
72.Moran A, Jacobs DR, Jr., Steinberger J, et al. Changes in insulin resistance and cardiovascular risk during adolescence: establishment of differential risk in males and females. Circulation 2008;117:2361-8.
73.Chiu KC, Cohan P, Lee NP, Chuang LM. Insulin sensitivity differs among ethnic groups with a compensatory response in beta-cell function. Diabetes Care 2000;23:1353-8.
74.Donahue RP, Bean JA, Donahue RA, Goldberg RB, Prineas RJ. Insulin response in a triethnic population: effects of sex, ethnic origin, and body fat. Miami Community Health Study. Diabetes Care 1997;20:1670-76.
75.Sumner AE, Kushner H, Sherif KD, Tulenko TN, Falkner B, Marsh JB. Sex differences in African-Americans regarding sensitivity to insulin''s glucoregulatory and antilipolytic actions. Diabetes Care 1999;22:71-7.
76.Rincon J, Holmang A, Wahlstrom EO, et al. Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment. Diabetes 1996;45:615-21.
77.吳家雯. 全民健康保險研究資料庫HMG-CoA Reductase Inhibitors處方型態及用藥安全性分析:自藥品交互作用觀點探討. In: 國立台灣大學醫學院臨床藥學研究所; 2005.
78.Ratz Bravo AE, Tchambaz L, Krahenbuhl-Melcher A, Hess L, Schlienger RG, Krahenbuhl S. Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy. Drug Saf 2005;28:263-75.
79.Efficacy of atorvastatin in primary hypercholesterolemia. Japan Cholesterol Lowering Atorvastatin Study (J-CLAS) Group. Am J Cardiol 1997;79:1248-52.
80.Pravastatin use and risk of coronary events and cerebral infarction in japanese men with moderate hypercholesterolemia: the Kyushu Lipid Intervention Study. J Atheroscler Thromb 2000;7:110-21.
81.Nakamura H. Primary prevention of cardiovascular diseases among hypercholesterolemic Japanese with a low dose of pravastatin. Atheroscler Suppl 2007;8:13-7.
82.Saito Y, Goto Y, Dane A, Strutt K, Raza A. Randomized dose-response study of rosuvastatin in Japanese patients with hypercholesterolemia. J Atheroscler Thromb 2003;10:329-36.
83.Sasaki J, Arakawa K, Iwashita M, Matsushita Y, Kono S. Reduction in serum total cholesterol and risks of coronary events and cerebral infarction in Japanese men: the Kyushu Lipid Intervention Study. Circ J 2003;67:473-8.
84.Wang KY, Ting CT. A randomized, double-blind, placebo-controlled, 8-week study to evaluate the efficacy and safety of once daily atorvastatin (10 mg) in patients with elevated LDL-cholesterol. Jpn Heart J 2001;42:725-38.
85.Wu CC, Sy R, Tanphaichitr V, Hin AT, Suyono S, Lee YT. Comparing the efficacy and safety of atorvastatin and simvastatin in Asians with elevated low-density lipoprotein-cholesterol--a multinational, multicenter, double-blind study. J Formos Med Assoc 2002;101:478-87.
86.Yamamoto A, Arakawa K, Sasaki J, et al. Clinical effects of rosuvastatin, a new HMG-CoA reductase inhibitor, in Japanese patients with primary hypercholesterolemia: an early phase II study. J Atheroscler Thromb 2002;9:48-56.
87.Saito M, Hirata-Koizumi M, Urano T, Miyake S, Hasegawa R. A literature search on pharmacokinetic drug interactions of statins and analysis of how such interactions are reflected in package inserts in Japan. J Clin Pharm Ther 2005;30:21-37.
88.Romero-Gomez M, Miralles EJ, EG D. Hepatotoxicity induced by fosinopril. J Hepatol 2001;35:309.
89.Jeserich M, Ihling C, H-P A. Acute liver failure due to enalapril. HERZ 2000; 25(7):689-693.
90.Bristol-Myers Squibb Co. Product Information: Capoten(R), captopril. . 1996.
91.Hagley MT, Hulisz DT, CM: B. Hepatotoxicity associated with angiotensin-converting enzyme inhibitors. . Ann Pharmacother 1993;27:228.
92.Nunes ACR, Amaro P, F M. Fosinopril-induced prolonged cholestatic jaundice and pruritus: first case report. Eur J Gastroenterolo Hepatol 2001;13:279.
93.Deira JL, Corbacho L, A B. Captopril hepatotoxicity in a case of renal crisis due to systemic sclerosis Nephrol Dial Transplant 1997;12:1717.
94.Guo JJ, Wigle PR, Lammers K, Vu O. Comparison of potentially hepatotoxic drugs among major US drug compendia. Res Social Adm Pharm 2005;1:460-79.
95.Hilburn RB, Bookstaver D, WL W. Comment: angiotensin-converting enzyme inhibitor hepatotoxicity: further insights Ann Pharmacother 1993;27:1142.
96.MICROMEDEX 2008. (Accessed May,15, 2008, at
97.Andrade RJ, Lucena MI, Fernandez MC, et al. Cholestatic hepatitis related to use of irbesartan: a case report and a literature review of angiotensin II antagonist-associated hepatotoxicity. Eur J Gastroenterol Hepatol 2002;14:887-90.
98.Basile G, Villari D, Gangemi S, Ferrara T, Accetta MG, Nicita-Mauro V. Candesartan cilexetil-induced severe hepatotoxicity. J Clin Gastroenterol 2003;36:273-5.
99.Bosch X. Losartan-induced hepatotoxicity. JAMA 1997;278:1572.
100.Lahoti S, Lee WM. Hepatotoxicity of anticholesterol, cardiovascular, and endocrine drugs and hormonal agents. Gastroenterol Clin North Am 1995;24:907-22.
101.Nygaard B, Strandgaard S. Marked hepatotoxicity associated with losartan treatment. Blood Press 1996;5:190-1.
102.Herman RJ. Drug interactions and the statins. CMAJ 1999;161:1281-6.
103.de Arriba G, Garcia-Martin F, Sanchez-Heras M, Aldeguer M, Tejero E, Jarillo MD. Hepatotoxicity due to verapamil hydrochloride. Eur J Med 1993;2:179-81.
104.Kumar KL, Colley CA. Verapamil-induced hepatotoxicity. West J Med 1994;160:485-6.
105.Lafuente NG. Calcium channel blockers and hepatotoxicity. Am J Gastroenterol 2000;95:2145.
106.Stravitz RT, Sanyal AJ. Drug-induced steatohepatitis. Clin Liver Dis 2003;7:435-51.
107.Chon EM, Middleton RK. Labetalol hepatotoxicity. Ann Pharmacother 1992;26:344-5.
108.Hagmeyer KO, Stein J. Hepatotoxicity associated with carvedilol. Ann Pharmacother 2001;35:1364-6.
109.Marinella MA. Labetalol-induced hepatitis in a patient with chronic hepatitis B infection. J Clin Hypertens (Greenwich) 2002;4:120-1.
110.Isley WL. Hepatotoxicity of thiazolidinediones. Expert Opin Drug Saf 2003;2:581-6.
111.Alsheikh-Ali AA, Abourjaily HM, Karas RH. Risk of adverse events with concomitant use of atorvastatin or simvastatin and glucose-lowering drugs (thiazolidinediones, metformin, sulfonylurea, insulin, and acarbose). Am J Cardiol 2002;89:1308-10.
112. Alander SW, Dowd MD, Bratton SL, Kearns GL. Pediatric acetaminophen overdose: risk factors associated with hepatocellular injury. Arch Pediatr Adolesc Med 2000;154:346-50.
113. Bongiovanni M, Cicconi P, Landonio S, et al. Predictive factors of lopinavir/ritonavir discontinuation for drug-related toxicity: results from a cohort of 416 multi-experienced HIV-infected individuals. Int J Antimicrob Agents 2005;26:88-91.
114. Gil AC, Lorenzetti R, Mendes GB, et al. Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy. Sao Paulo Med J 2007;125:205-9.
115. Schaberg T, Rebhan K, Lode H. Risk factors for side-effects of isoniazid, rifampin and pyrazinamide in patients hospitalized for pulmonary tuberculosis. Eur Respir J 1996;9:2026-30.
116. .羅敏. 結合病人使用抗結核藥物所致肝毒性之回溯性分析研究. 台灣大學碩士論文 1999.
117. Wang P. Epidemiology and control of tuberculosis in Taipei. J infect 2002;45:82.
118. 陳映蓉. 抗結核藥物致肝毒性之前瞻性研究. 國立台灣大學碩士論文 2002.
119. 蕭斐元. 預測抗結核藥物治療期間肝毒性之評分系統的建立. 台北醫學大學碩士論文 2003. 120. Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. . Am J Respir crit Care Med 2003;167:1472.
121. Tedaldi EM, Absalon J, Thomas AJ, Shlay JC, van den Berg-Wolf M. Ethnicity, race, and gender. Differences in serious adverse events among participants in an antiretroviral initiation trial: results of CPCRA 058 (FIRST Study). J Acquir Immune Defic Syndr 2008;47:441-8
122. Abboud G, Kaplowitz N. Drug-induced liver injury. Drug Safty 2007;30:277-94.
123. 蔡春玉, 曾彥閔, 陳玉瑩, 許光陽, 陳恆德. 使用HMG-CoA 還原酶抑制劑病患的肝功能檢測之探討--以某醫學中心為例. Drug Safety Newsletter 2006;14.
124. Andrade SE, Donahue JG, Chan KA, Watson DJ, Platt R. Liver function testing in patients on HMG-CoA reductase inhibitors. Pharmacoepidemiol Drug Saf 2003;12:307-13.
125.中央健保局.藥品使用量分析.2003.(Accessed May, 28, 2008, at http://www.nhi.gov.tw/webdata/webdata.asp?menu=1&menu_id=56&webdata_id=1172&WD_ID=.)
126. National Cancer Institution. Common Terminology Criteria for Adverse Events v3.0(CTCAE). 2006. (Accessed at http://ctep.cancer.gov/forms/CTCAEv3.pdf.)
127. Yang SY, Kao Yang YH, Chong MY, Yang YH, Chang WH, Lai CS. Risk of extrapyramidal syndrome in schizophrenic patients treated with antipsychotics: a population-based study. Clin Pharmacol Ther 2007;81:586-94.
128. Patten S, Cipriani A, Brambilla P, Nose M, Barbui C. International dosage differences in fluoxetine clinical trials. Can J Psychiatry 2005;50:31-8.
129. Thomas SV, Koshy S, Nair CR, Sarma SP. Frequent seizures and polytherapy can impair quality of life in persons with epilepsy. Neurol India 2005;53:46-50.
130. Hach I, Maywald U, Meusel D, Konig JU, Kirch W. Continuity of long-term medication use after surgical hospital stay. Eur J Clin Pharmacol 2005;61:433-8.
131. Talmor D, Jones AE, Rubinson L, Howell MD, Shapiro NI. Simple triage scoring system predicting death and the need for critical care resources for use during epidemics. Crit Care Med 2007;35:1251-6.
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