臺灣博碩士論文加值系統

過去幾年中草藥使用逐漸風行，同時中藥引發健康危害也越來越被關注。世界上很少有有關於中草藥與肝不良反應的流行病學研究。中醫藥是台灣健康照護系統上的一個重要角色，全民健康保險給付幾乎所有的濃縮中藥。我們使用個案交叉研究來分析1997-2002年全民健保20萬抽樣歸人，試圖觀察中草藥處方與急性肝炎住院間的關連。
結果發現30天應該是處方後到急性肝炎間的時間。調整後顯著效應的是其他急性肝炎，以及急性B型肝炎兩組，勝算比分別是5.53 (95％信賴區間是2.05到14.89) 及2.17 (95％信賴區間是1.01到4.68)。以時序性，累積劑量跟再服用來分析可能肝毒性中藥與西藥在這兩個族群的服用狀況，我們發現其中12位個案服用可能肝毒性中藥，與住院可能有因果關係，其中8位住院超過一個禮拜。之前研究過可能肝毒性中藥，黃芩，柴胡，麻黃，白朮，甘草，牡丹皮，白鮮皮，芍藥，在我們研究中也發現可能與住院有關。另外，延胡索，黃連，茵陳，川楝子這些之前很少或沒報導過的中藥也懷疑與住院有關。
我們的研究提供了在中國社會關於中草藥使用者一些安全資訊，證明使用中草藥增加急性肝炎住院危險。民眾與醫師應該注意這個發現，並在服用中草藥，特別是這些肝毒性中草藥時要注意。我們建議未來進一步進行系統性對這些肝毒性中草藥不良反應通報與主動監測。

Although the increase in popularity of herbal products in past years, there has been a growing concern about health hazards caused by Chinese herbs. There are few epidemiological studies addressing the relationship between Chinese herbs and hepatic adverse effects worldwide. In Taiwan, Chinese herbal medicines (CHMs) play an important role of health care system and payments of Bureau of National Health Insurance apply to most CHMs in concentrated form. We attempted to determine the relation between the hospitalization related to acute hepatitis and CHMs prescriptions. We designed a case-crossover study by using the database of 200,000 people randomly sampled from the National Health Insurance during 1997-2002.
We found 30 days were the most probable time to event. The significant adjusted odds ratio was the population of other acute hepatitis, 5.53 (95% confidence interval: 2.05 to 14.89) and acute hepatitis B 2.17 (95% confidence interval: 1.01 to 4.68). By the temporal sequence, cumulative dose and challenge assessment of 32 case with hepatoxic CHMs and western medicines in two groups, we found 12 cases having relation with hepatoxic CHMs possibly and eight of them were admitted for more than one week. The hepatoxic CHMs that had been reported, Radix Scutellariae, Radix Bupleuri, Herba Ephedrae, Rhizoma Atracylodis Macrocephalac, Radix Glycyrrhizae, Cortex Moutan, Cortex Dictamni, and Radix Paeoniae was also possibly causal to hospitalization. Further, Corydalis decumbens, Herba Artemisiae Scopariae, Rhizoma Coptidis and Fructus Toosendan less or no reported previously were suspected with causal relation to hospitalization.
Our results can provide some safety information about CHMs users in Chinese society to demonstrate increased hospitalization related to acute hepatitis in Chinese herbs users. People and physicians should take into account this finding and should be aware of possible ingestion of herbal medicines, especially these suspected hepatoxic CHMs. We recommend that it is important to conduct systematic Chinese herbal pharmacovigilance and active surveillance study for these hepatotoxic CHMs in the near future.

LIST OF TABLES 4
ABSTRACT 5
INTRODUCTION 8
MATERIAL AND METHODS 10
Data sources 10
Study subjects 11
Case-crossover design 11
Time windows 12
The exposure window 12
The washout period 12
Time series 12
Covariates 13
Western medicines with hepatotoxicity 13
Chinese herbal medicines 13
Case assessments 14
Statistical methods 15
RESULTS 16
DISCUSSION 19
CONCLUSIONS AND IMPLICATIONS 26
REFERENCES 27
APPENDICES 37
Table 3 37
Table 4 40

1.Kessler RC, Davis RB, Foster DF et al. Long-term trends in the use of complementary and alternative medical therapies in the United States. Ann Intern Med 2001;135(4):262-268.
2.Deng JF, Lin TJ, Kao WF, Chen SS. The difficulty in handling poisonings associated with Chinese traditional medicine: a poison control center experience for 1991-1993. Vet Hum Toxicol 1997;39(2):106-114.
3.De Smet PA. Health risks of herbal remedies. Drug Saf 1995;13(2):81-93.
4.Haller CA, Dyer JE, Ko R, Olson KR. Making a diagnosis of herbal-related toxic hepatitis. West J Med 2002;176(1):39-44.
5.Chen CJ, Wang LY, Chien YC. News from Taiwan. Hepatology 2004;39(5):1196.
6.Strader DB, Bacon BR, Lindsay KL et al. Use of complementary and alternative medicine in patients with liver disease. Am J Gastroenterol 2002;97(9):2391-2397.
7.Chen TJ, Chou LF, Hwang SJ. Utilization of hepatoprotectants within the National Health Insurance in Taiwan. J Gastroenterol Hepatol 2003;18(7):868-872.
8.Maclure M. The case-crossover design: a method for studying transient effects on the risk of acute events. Am J Epidemiol 1991;133(2):144-153.
9.Wang PS, Schneeweiss S, Glynn RJ, Mogun H, Avorn J. Use of the case-crossover design to study prolonged drug exposures and insidious outcomes. Ann Epidemiol 2004;14(4):296-303.
10.Itoh S, Marutani K, Nishijima T, Matsuo S, Itabashi M. Liver injuries induced by herbal medicine, syo-saiko-to (xiao-chai-hu-tang). Dig Dis Sci 1995;40(8):1845-1848.
11.Borum ML. Fulminant exacerbation of autoimmune hepatitis after the use of ma huang. Am J Gastroenterol 2001;96(5):1654-1655.
12.Park GJ, Mann SP, Ngu MC. Acute hepatitis induced by Shou-Wu-Pian, a herbal product derived from Polygonum multiflorum. J Gastroenterol Hepatol 2001;16(1):115-117.
13.Melchart D, Linde K, Weidenhammer W, Hager S, Shaw D, Bauer R. Liver enzyme elevations in patients treated with traditional Chinese medicine. JAMA 1999;282(1):28-29.
14.Kane JA, Kane SP, Jain S. Hepatitis induced by traditional Chinese herbs; possible toxic components. Gut 1995;36(1):146-147.
15.Wen KC. The Turnover Rate of Marker Constituents in TCM. J Food and Drug Anal 2000;8(4):207-277.
16.Department of Health T. Health and national health insurance annual statistics in Taiwan. Available at: http://www.doh.gov.tw/statistic/index.htm Accessed May 16, 2005
17.Nguyen MH, Garcia G. Does isoniazid cause more serious hepatotoxicity in hepatitis B virus carriers? Am J Gastroenterol 2002;97(5):1092-1093.
18.Siddiqui U, Weinshel EH, Bini EJ. Prevalence and predictors of herbal medication use in veterans with chronic hepatitis C. J Clin Gastroenterol 2004;38(7):605-610.
19.Schneeweiss S STMM. Case-crossover and case-time-control designs as alternatives in pharmacoepidemiologic research. Pharmacoepidemiol Drug Saf 1997; Suppl 3(6):S51-S59.
20.Suissa S. The case-time-control design. Epidemiology 1995;6(3):248-253.
21.Greenland S. Confounding and exposure trends in case-crossover and case-time-control designs. Epidemiology 1996;7(3):231-239.
22.Kamiyama T, Nouchi T, Kojima S, Murata N, Ikeda T, Sato C. Autoimmune hepatitis triggered by administration of an herbal medicine. Am J Gastroenterol 1997;92(4):703-704.
23.Yeung CY, Lee FT, Wong HN. Effect of a popular Chinese herb on neonatal bilirubin protein binding. Biol Neonate 1990;58(2):98-103.
24.Gorey JD WMBNW. Adverse reaction to a Chinese herbal remedy. Med J Aust 1992;157:484-486..
25.Horowitz RS, Feldhaus K, Dart RC, Stermitz FR, Beck JJ. The clinical spectrum of Jin Bu Huan toxicity. Arch Intern Med 1996;156(8):899-903.
26.Unerversity of Wstern Syndey CMUA, editor. Chinese Herbal Medicines Toxicology Database. Ku lian gen pi. 2001.
27.Donnan PT, Wang J. The case-crossover and case-time-control designs in pharmacoepidemiology. pharmacoepidemiology. Pharmacoepidemiol Drug Saf 2001;10(3):259-262.
28.Perharic L, Shaw D, Colbridge M, House I, Leon C, Murray V. Toxicological problems resulting from exposure to traditional remedies and food supplements. Drug Saf 1994;11(4):284-294.