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Clinical Features and Outcomes of Complementary and Alternative Medicine Induced Acute Liver Failure and Injury

Hillman, Luke MD1; Gottfried, Michelle MS2; Whitsett, Maureen MD1; Rakela, Jorge MD3; Schilsky, Michael MD4; Lee, William M MD5; Ganger, Daniel MD6

American Journal of Gastroenterology: July 2016 - Volume 111 - Issue 7 - p 958–965
doi: 10.1038/ajg.2016.114

OBJECTIVES: The increasing use of complementary and alternative medicines (CAMs) has been associated with a rising incidence of CAM-induced drug-induced liver injury (DILI). The aim of this study was to examine the clinical features and outcomes among patients with acute liver failure (ALF) and acute liver injury (ALI) enrolled in the Acute Liver Failure Study Group database, comparing CAM-induced with prescription medicine (PM)-induced DILI.

METHODS: A total of 2,626 hospitalized patients with ALF/ALI of any etiology were prospectively enrolled between 1998 and 2015 from 32 academic transplant centers. Only those with CAM or PM-induced ALI/ALF were selected for analysis.

RESULTS: A total of 253 (9.6%) subjects were found to have idiosyncratic DILI, of which 41 (16.3%) were from CAM and 210 (83.7%) were due to PM. The fraction of DILI-ALF/ALI cases due to CAM increased from 1998–2007 to 2007–2015 (12.4 vs. 21.1%,P=0.047). There was no difference in the type of liver injury—hepatocellular, cholestatic, or mixed—between groups as determined byRscore (P=0.26). PM-induced DILI showed higher serum alkaline phosphatase levels compared with the CAM group (median IU/L, 171 vs. 125,P=0.003). The CAM population had fewer comorbid conditions (1.0 vs. 2.0,P<0.005), higher transplantation rates (56 vs. 32%,P<0.005), and a lower ALF-specific 21-day transplant-free survival (17 vs. 34%,P=0.044).

CONCLUSIONS: CAM-induced DILI is at least as severe in presentation as that observed due to PM with higher rates of transplantation and lower transplant-free survival in those who progress to ALF. This study highlights the increasing incidence of CAM-induced liver injury and emphasizes the importance of early referral and evaluation for liver transplantation when CAM-induced liver injury is suspected.

1Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

2Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA

3Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, Arizona, USA

4Division of Digestive Diseases and Transplantation and Immunology, Departments of Medicine and Surgery, Yale University, New Haven, Connecticut, USA

5Department of Medicine, Division of Digestive and Liver Diseases, UT Southwestern Medical Center at Dallas, Dallas, Texas, USA

6Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

Correspondence: Luke Hillman, MD, Department of Medicine, Northwestern University Feinberg School of Medicine, 251 E Huron Street, Galter Suite 3-150, Chicago, Illinois, USA. E-mail:

SUPPLEMENTARY MATERIAL accompanies this paper at

Received 01 January 2016; accepted 02 February 2016

Guarantors of the article: Luke Hillman, MD and Daniel Ganger, MD.

Specific author contributions: Statistical analysis: Luke Hillman, Michelle Gottfried, and Daniel Ganger. All authors participated in data acquisition, analysis or interpretation of data. All authors were responsible for drafting, critical revision, and approval of the final manuscript.

Financial support: The Acute Liver Failure Study Group is funded principally by the National Institutes of Health, under grant U01 DK058369.

Potential competing interests: William M. Lee provides consulting services to Novartis, Sanofi and Lilly and receives research support from BMS, Gilead and Merck. The remaining authors declare no conflict of interest.

© The American College of Gastroenterology 2016. All Rights Reserved.
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