title: Drug-induced liver injury associated with Complementary and Alternative Medicine: a review of adverse event reports in an Asian community from 2009 to 2014.
abstract: BACKGROUND
  The use of Complementary and Alternative Medicine (CAM) has been increasing over the years. A recent review of adverse event reports (AERs) associated with CAM in Singapore found a notable number of AERs submitted. The objectives of this study are to analyse hepatotoxicity cases associated with CAM in Singapore based on spontaneous adverse event reporting to the Health Sciences Authority (HSA), and to highlight safety signals for specific herbal ingredients.
  
  
  METHODS
  AERs associated with CAM and hepatotoxicity submitted to the Vigilance and Compliance Branch (VCB) of the HSA from 2009 to 2014 were compiled. The following information was extracted and analysed: Demographic information; time to onset; hospitalisation status; outcome; type of hepatotoxicity; ingredients of CAM, and the total daily doses (TDD); concurrent western medicines and health supplements; and reporter details.
  
  
  RESULTS
  Fifty-seven reports were eligible for analysis. Thirty-five (61.4 %) cases involved Traditional Chinese Medicine (TCM). The Roussel Uclaf Causality Assessment Method was applied in 29 (82.9 %) of these cases, and the median score was 4 (range: 1-8). Chai Hu (Radix bupleuri) was suspected in 11 (31.4 %) cases. TDDs of most ingredients were within recommended doses of the Chinese Pharmacopoeia.
  
  
  CONCLUSIONS
  Drug-induced liver injury is still poorly understood and more objective assessments are warranted. Reporting of adverse events should be strongly advocated to facilitate future analyses and the understanding of risk-benefit profiles of CAM.
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A Level 3, 18 Science Drive 4, Singapore, S117543, Republic of Singapore.
authors.forename: Desmond Chun Hwee
authors.initials: DC
authors.lastname: Teo
authors.affiliation: Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667, Singapore.
authors.forename: Patricia Suet Leng
authors.initials: PS
authors.lastname: Ng
authors.affiliation: Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667, Singapore.
authors.forename: Siew Har
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667, Singapore.
authors.forename: Adena Theen
authors.initials: AT
authors.lastname: Lim
authors.affiliation: Vigilance and Compliance Branch, Health Sciences Authority Singapore, 11 Biopolis Way, #11-03, Helios, Singapore, 138667, Singapore.
authors.forename: Dorothy Su Lin
authors.initials: DS
authors.lastname: Toh
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A Level 3, 18 Science Drive 4, Singapore, S117543, Republic of Singapore.
authors.forename: Sui Yung
authors.initials: SY
authors.lastname: Chan
authors.affiliation: Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A Level 3, 18 Science Drive 4, Singapore, S117543, Republic of Singapore. hanhui_cheong@nus.edu.sg.|Department of Pharmacy, KK Women's and Children's Hospital, 100 Bukit Timah Road, Singapore, 229899, Singapore. hanhui_cheong@nus.edu.sg.
authors.forename: Han Hui
authors.identifier: http://orcid.org/0000-0002-8616-4529
authors.initials: HH
authors.lastname: Cheong
mesh_terms: D000293:Adolescent; D000328:Adult; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology*; D002648:Child; D002675:Child, Preschool; D000529:Complementary Therapies / Q000009:adverse effects* / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012846:Singapore / Q000453:epidemiology; D055815:Young Adult
keywords: Adverse event; Complementary and Alternative Medicine; Hepatotoxicity; Traditional Chinese Medicine