Risk of liver injury associated with Chinese herbal products containing radix bupleuri in 639,779 patients with hepatitis B virus infection.
BACKGROUND
Chinese herbal products (CHPs) containing radix bupleuri are often prescribed for chronic hepatitis. There have been no epidemiological studies in populations with hepatitis B virus (HBV) infection. Our study was conducted to determine the association between the use of CHPs containing radix bupleuri and the risk of hospitalisation related to liver injury among HBV-infected patients in Taiwan.


METHODS
From a total of 639,779 patients with diagnoses related to HBV infection, we included hospitalised adult cases with a primary diagnosis of liver injury in the database of Taiwan's national health insurance during the period 1997-2004. Case-control and case-crossover designs were used to assess the risk of hospitalisation with conditional logistic regression models constructed and adjusted for 270 conventionally hepatotoxic drugs. Cumulative doses of these CHPs and radix bupleuri were assessed for any dose-response relationship.


RESULTS
In total, we collected 1,080 cases fulfilled the inclusion criteria. In the case-control design, the adjusted odds ratio was 1.90 (95% confidence interval [CI]: 1.30 to 2.77). The risks from prescribing the CHPs Xiao-Chai-Hu-Tang and Long-Dan-Xie-Gan-Tang were significantly high, and dose-response relationships were found. The risk of adding each 19 gm dose of radix bupleuri was 2.19 (95% CI: 1.66 to 2.89). The results using the case-crossover design remained similar.


CONCLUSIONS
Prescribing Xiao-Chai-Hu-Tang, Long-Dan-Xie-Gan-Tang, or CHPs containing more than 19 gram of radix bupleuri in HBV-infected patients might increase their risks of liver injury. Further studies are indicated to corroborate the above findings.
Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan.
Chang-Hsing
CH
Lee
Jung-Der
JD
Wang
Pau-Chung
PC
Chen
D000293:Adolescent; D000328:Adult; D029972:Bupleurum / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy / Q000453:epidemiology*; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D010936:Plant Extracts / Q000009:adverse effects*; D012306:Risk; D013624:Taiwan; D055815:Young Adult
C051274:Bupleurum root extract; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts
J Chin Med Assoc. 2006 Feb;69(2):86-8
16570576
Semin Liver Dis. 2002;22(2):145-55
12016546
Phytomedicine. 2002 May;9(4):280-7
12120808
Cancer. 1995 Sep 1;76(5):743-9
8625175
Lancet. 1990 Jul 21;336(8708):177
1973490
JAMA. 1999 Jul 7;282(1):28-9
10404907
Aliment Pharmacol Ther. 2006 Oct 15;24(8):1179-86
17014576
Hepatology. 2004 May;39(5):1196
15122745
Am J Gastroenterol. 1997 Apr;92(4):703-4
9128330
J Ethnopharmacol. 2008 Apr 17;117(1):84-91
18321671
Hum Exp Toxicol. 2006 Aug;25(8):481-94
16937920
Gut. 1995 Jan;36(1):146-7
7890220
Am J Gastroenterol. 2001 May;96(5):1654-5
11374728
Complement Ther Med. 2005 Sep;13(3):175-82
16150371
Dig Dis Sci. 1995 Aug;40(8):1845-8
7648990
West J Med. 2002 Jan;176(1):39-44
11788538
J Altern Complement Med. 2006 Apr;12(3):233-6
16646721
J Clin Epidemiol. 1992 Jun;45(6):613-9
1607900
J Gastroenterol Hepatol. 2001 Jan;16(1):115-7
11206309
Antivir Ther. 2007;12(3):285-95
17591018