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Publication Information
Affiliation
Liver Disease Research Branch, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Bethesda, MD.
2National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD.
3Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
4Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
5Duke Clinical Research Institute, Duke University, Durham, NC.
6Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
7University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA.
8Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI.
9National Center for Natural Products Research, University of Mississippi, University, MI.
10The Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD.
11Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD.
12Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC.
13Department of Medicine, Einstein Healthcare Network, Philadelphia, PA.
14Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA.
15Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, NC.
16Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
Authors
Ahmad J, Barnhart H, Bonkovsky HL, Durazo F, Fontana RJ, Gu J, Hoofnagle JH, Khan I, Kleiner DE, Koh C, Li Y-J, Navarro VJ, Phillips EJ, Rockey DC, Seeff LB, Serrano J, Stolz A, Tillmann HL, Vuppalanchi R
Studies
Abstract
Background and aims: Herbal supplements, and particularly multi-ingredient products, have become increasingly common causes of acute liver injury. Green tea is a frequent component in implicated products, but its role in liver injury is controversial. The aim of this study was to better characterize the clinical features, outcomes, and pathogenesis of green tea-associated liver injury.
Approach and results: Among 1,414 patients enrolled in the U.S. Drug-Induced Liver Injury Network who underwent formal causality assessment, 40 cases (3%) were attributed to green tea, 202 to dietary supplements without green tea, and 1,142 to conventional drugs. The clinical features of green tea cases and representation of human leukocyte antigen (HLA) class I and II alleles in cases and control were analyzed in detail. Patients with green tea-associated liver injury ranged in age from 17 to 69 years (median = 40) and developed symptoms 15-448 days (median = 72) after starting the implicated agent. The liver injury was typically hepatocellular (95%) with marked serum aminotransferase elevations and only modest increases in alkaline phosphatase. Most patients were jaundiced (83%) and symptomatic (88%). The course was judged as severe in 14 patients (35%), necessitating liver transplantation in 3 (8%), but rarely resulting in chronic injury (3%). In three instances, injury recurred upon re-exposure to green tea with similar clinical features, but shorter time to onset. HLA typing revealed a high prevalence of HLA-B*35:01, found in 72% (95% confidence interval [CI], 58-87) of green tea cases, but only 15% (95% CI, 10-20) caused by other supplements and 12% (95% CI, 10-14) attributed to drugs, the latter rate being similar to population controls (11%; 95% CI, 10.5-11.5).
Conclusions: Green tea-related liver injury has distinctive clinical features and close association with HLA-B*35:01, suggesting that it is idiosyncratic and immune mediated.