HLA-B*35:01 and Green Tea-Induced Liver Injury.


Journal

Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946

Informations de publication

Date de publication:
06 2021
Historique:
revised: 25 07 2020
received: 04 06 2020
accepted: 16 08 2020
pubmed: 7 9 2020
medline: 8 1 2022
entrez: 6 9 2020
Statut: ppublish

Résumé

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. 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). 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.

Sections du résumé

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.

Identifiants

pubmed: 32892374
doi: 10.1002/hep.31538
pmc: PMC8052949
mid: NIHMS1681562
doi:

Substances chimiques

HLA-B Antigens 0
Tea 0
Transaminases EC 2.6.1.-

Types de publication

Journal Article Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2484-2493

Subventions

Organisme : NIDDK NIH HHS
ID : P30 DK123704
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK065176
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK083020
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM130457
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK065184
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK065211
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK083027
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK065201
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK100928
Pays : United States

Informations de copyright

© 2020 by the American Association for the Study of Liver Diseases.

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Auteurs

Jay H Hoofnagle (JH)

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.

Herbert L Bonkovsky (HL)

National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD.
Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.

Elizabeth J Phillips (EJ)

Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.

Yi-Ju Li (YJ)

Duke Clinical Research Institute, Duke University, Durham, NC.

Jawad Ahmad (J)

Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

Huiman Barnhart (H)

Duke Clinical Research Institute, Duke University, Durham, NC.

Francisco Durazo (F)

University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA.

Robert J Fontana (RJ)

Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI.

Jiezhun Gu (J)

Duke Clinical Research Institute, Duke University, Durham, NC.

Ikhlas Khan (I)

National Center for Natural Products Research, University of Mississippi, University, MI.

David E Kleiner (DE)

The Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD.

Christopher Koh (C)

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD.

Don C Rockey (DC)

Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC.

Leonard B Seeff (LB)

Department of Medicine, Einstein Healthcare Network, Philadelphia, PA.

Jose Serrano (J)

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.

Andrew Stolz (A)

Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA.

Hans L Tillmann (HL)

Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, NC.

Raj Vuppalanchi (R)

Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.

Victor J Navarro (VJ)

Department of Medicine, Einstein Healthcare Network, Philadelphia, PA.

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