The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
HLA‐B*35:01 and Green Tea–Induced Liver Injury
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“HLA polymorphisms shown to be significantly associated with multiple drugs include HLA-A*02:01 for AC and cefazolin DILI and HLA-B*35:01 for multiple HDS products, including green tea extract, turmeric, and Polygonum multiform.”
From The contemporary epidemiology, causes, and management of drug-induced liver injury (2026) · cites this paper as [32]
In the citing paper
“Interestingly, HLA-B*35:01 was associated with turmeric hepatotoxicity, as it had been previously associated with green tea extract hepatotoxicity. 32”
From The contemporary epidemiology, causes, and management of drug-induced liver injury (2026) · cites this paper as [32]
In the citing paper
“A focused analysis of GTE cases enrolled in the DILIN has led to recognition of the typical presentation of GTE as being hepatocellular and sometimes fatal, with a strong genetic association with HLA‐B*35:01.72”
From AASLD practice guidance on drug, herbal, and dietary supplement–induced liver injury (2023) · cites this paper as [72]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin
study, F. T. D., Daly, A. K., International SAE Consortium, Donaldson, P. T., Bhatnagar, P., Shen, Y., Pe'er, I., Floratos, A., Daly, M. J., Goldstein, D. B., et al. (2009) · Nature Genetics · doi:10.1038/ng.379 · Cited by 944
Features and outcomes of 899 patients with drug-induced liver injury: the DILIN Prospective Study
Chalasani, N., Bonkovsky, H. L., Fontana, R., Lee, W., Stolz, A., Talwalkar, J., Reddy, K. R., Watkins, P. B., Navarro, V., Barnhart, H., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.03.006 · Cited by 925
Self-citationGreen Tea Consumption and Mortality Due to Cardiovascular Disease, Cancer, and All Causes in Japan
Kuriyama, S., Shimazu, T., Ohmori, K., Kikuchi, N., Nakaya, N., Nishino, Y., Tsubono, Y., & Tsuji, I. (2006) · JAMA · doi:10.1001/jama.296.10.1255 · Cited by 763
Drug-induced liver injury—types and phenotypes
Hoofnagle, J. H., & Björnsson, E. S. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1816149 · Cited by 652
Self-citationDrug-Induced Liver Injury Network (DILIN) Prospective Study: Rationale, Design and Conduct
Fontana, R. J., Watkins, P. B., Bonkovsky, H. L., Chalasani, N., Davern, T., Serrano, J., & Rochon, J. (2009) · Drug Safety · doi:10.2165/00002018-200932010-00005 · Cited by 486
Self-citationLiver injury from herbal and dietary supplements
Navarro, V. J., Khan, I., Björnsson, E., Seeff, L. B., Serrano, J., & Hoofnagle, J. H. (2017) · Hepatology · doi:10.1002/hep.28813 · Cited by 462
Self-citationHepatotoxicity of high oral dose (−)-epigallocatechin-3-gallate in mice
Lambert, J. D., Kennett, M. J., Sang, S., Reuhl, K. R., Ju, J., & Yang, C. S. (2009) · Food and Chemical Toxicology · doi:10.1016/j.fct.2009.10.030 · Cited by 436
HIBAG—HLA genotype imputation with attribute bagging
Zheng, X., Shen, J., Cox, C. J., Wakefield, J. C., Ehm, M. G., Nelson, M. R., & Weir, B. S. (2013) · The Pharmacogenomics Journal · doi:10.1038/tpj.2013.18 · Cited by 427
Hepatotoxicity from green tea: a review of the literature and two unpublished cases
Mazzanti, G., Menniti‐Ippolito, F., Moro, P. A., Cassetti, F., Raschetti, R., Santuccio, C., & Mastrangelo, S. (2009) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-008-0610-7 · Cited by 421
Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network
Navarro, V. J., Barnhart, H., Bonkovsky, H. L., Davern, T., Fontana, R. J., Grant, L., Reddy, R. K., Seeff, L. B., Serrano, J., Sherker, A. H., et al. (2014) · Hepatology · doi:10.1002/hep.27317 · Cited by 418
Self-citationKleiner, D. E., Chalasani, N. P., Lee, W. M., Fontana, R. J., Bonkovsky, H. L., Watkins, P. B., Hayashi, P. H., Davern, T. J., Navarro, V., Reddy, R., et al. (2014) · Hepatology · doi:10.1002/hep.26709 · Cited by 396
Self-citationCellular and in vivo hepatotoxicity caused by green tea phenolic acids and catechins
Galati, G., Lin, A. L., Sultan, A. M., & O'Brien, P. J. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.09.014 · Cited by 383
Hy's law: predicting serious hepatotoxicity
Temple, R. (2006) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.1211 · Cited by 354
Rockey, D. C., Seeff, L. B., Rochon, J., Freston, J., Chalasani, N., Bonacini, M., Fontana, R. J., & Hayashi, P. H. (2010) · Hepatology · doi:10.1002/hep.23577 · Cited by 313
Self-citationSafety of Green Tea Extracts: A Systematic Review by the US Pharmacopeia
Sarma, D. N., Barrett, M. L., Chavez, M. L., Gardiner, P., Ko, R., Mahady, G. B., Marles, R. J., Pellicore, L. S., Giancaspro, G. I., & Low Dog, T. (2008) · Drug Safety · doi:10.2165/00002018-200831060-00003 · Cited by 308
Henning, S. M., Fajardo-Lira, C., Lee, H. W., Youssefian, A. A., Go, V. L. W., & Heber, D. (2003) · Nutrition and Cancer · doi:10.1207/s15327914nc4502_13 · Cited by 266
Saeed, M., Naveed, M., Arif, M. A., Kakar, M. U., Manzoor, R., El-Hack, M. E. A., Alagawany, M. M., Tiwari, R., Khandia, R., Munjal, A. K., et al. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.09.024 · Cited by 252
Nicoletti, P., Aithal, G. P., Bjornsson, E. S., Andrade, R. J., Sawle, A., Arrese, M., Barnhart, H. X., Bondon-Guitton, E., Hayashi, P. H., Bessone, F., et al. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.12.016 · Cited by 221
Self-citationHepatotoxicity Associated with Supplements Containing Chinese Green Tea (Camellia sinensis)
Bonkovsky, H. L. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-144-1-200601030-00020 · Cited by 192
Self-citationHepatotoxicity of green tea: an update
Mazzanti, G., Di Sotto, A., & Vitalone, A. (2015) · Archives of Toxicology · doi:10.1007/s00204-015-1521-x · Cited by 189
United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts
Oketch-Rabah, H. A., Roe, A. L., Rider, C. V., Bonkovsky, H. L., Giancaspro, G. I., Navarro, V., Paine, M. F., Betz, J. M., Marles, R. J., Casper, S., et al. (2020) · Toxicology Reports · doi:10.1016/j.toxrep.2020.02.008 · Cited by 168
Self-citationHepatotoxicity Due to Hydroxycut: A Case Series
Fong, T., Klontz, K. C., Cañas-Coto, A., Casper, S. J., Durazo, F. A., Davern, T. J., Hayashi, P. H., Lee, W. M., & Seeff, L. B. (2010) · The American Journal of Gastroenterology · doi:10.1038/ajg.2010.5 · Cited by 145
Self-citationDara, L., Hewett, J., & Lim, J. K. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.6999 · Cited by 138
Li, C., Rao, T., Chen, X., Zou, Z., Wei, A., Tang, J., Xiong, P., Li, P., Jing, J., He, T., et al. (2019) · Hepatology · doi:10.1002/hep.30660 · Cited by 138
For the Drug Induced Liver Injury Network (DILIN), Vega, M., Verma, M., Beswick, D., Bey, S., Hossack, J., Merriman, N., Shah, A., & Navarro, V. (2017) · Drug Safety · doi:10.1007/s40264-017-0547-9 · Cited by 120
Self-citationDiverse antioxidants protect against acetaminophen hepatotoxicity
Oz, H. S., McClain, C. J., Nagasawa, H. T., Ray, M. B., de Villiers, W. J. S., & Chen, T. S. (2005) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.20042 · Cited by 106
Acute hepatitis associated with the use of green tea infusions
Jimenez-Saenz, M., & Martinez-Sanchez, M. D. C. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2005.11.041 · Cited by 95
Yu, Z., Samavat, H., Dostal, A. M., Wang, R., Torkelson, C. J., Yang, C. S., Butler, L. M., Kensler, T. W., Wu, A. H., Kurzer, M. S., et al. (2017) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-17-0160 · Cited by 68
The role of HLA-A*33:01 in patients with cholestatic hepatitis attributed to terbinafine
Fontana, R. J., Cirulli, E. T., Gu, J., Kleiner, D. E., Ostrov, D. A., Phillips, E. J., Schutte, R. J., Barnhart, H. X., Chalasani, N., Watkins, P. B., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.08.004 · Cited by 54
Self-citationNavarro, V., Avula, B., Khan, I., Verma, M., Seeff, L., Serrano, J., Stolz, A., Fontana, R., & Ahmad, J. (2019) · Hepatology Communications · doi:10.1002/hep4.1346 · Cited by 52
Self-citationSerious adverse liver reactions associated with herbal weight-loss supplements
Bjornsson, E. S., & Olsson, R. (2007) · Journal of Hepatology · doi:10.1016/j.jhep.2007.05.010 · Cited by 51
The Dietary Supplement Label Database: Recent Developments and Applications
Dwyer, J. T., Bailen, R. A., Saldanha, L. G., et al. (2018) · Journal of Nutrition · doi:10.1093/jn/nxy082 · Cited by 28
Zheng, E. X., Rossi, S., Fontana, R. J., Vuppalanchi, R., Hoofnagle, J. H., Khan, I. A., & Navarro, V. J. (2016) · Drug Safety · doi:10.1007/s40264-016-0428-7 · Cited by 25
Self-citationThe Opportunity of CBD — Reforming the Law
Cohen, P. A., & Sharfstein, J. (2019) · New England Journal of Medicine · doi:10.1056/nejmp1906409 · Cited by 17
Fulminant Hepatic Failure After Use of the Herbal Weight-Loss Supplement Exilis
McDonnell, W. M., Bhattacharya, R., & Halldorson, J. B. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-151-9-200911030-00021 · Cited by 16
Research works printed but not linked: 2
- 2010, Black cohosh products and liver toxicity: update, Can Adverse Reaction Newsletter, 20, 1
- 2015, Drug‐induced liver injury in the United States: a report of 899 events prospectively assessed, Gastroenterology, 148, 1340
Cited by
ACG Clinical Guideline: Diagnosis and Management of Idiosyncratic Drug-Induced Liver Injury
Chalasani, N. P., Maddur, H., Russo, M. W., Wong, R. J., Reddy, K. R., & on behalf of the Practice Parameters Committee of the American College of Gastroenterology (2021) · American Journal of Gastroenterology · doi:10.14309/ajg.0000000000001259 · Cited by 430
AASLD practice guidance on drug, herbal, and dietary supplement–induced liver injury
Fontana, R. J., Liou, I., Reuben, A., Suzuki, A., Fiel, M. I., Lee, W., & Navarro, V. (2023) · Hepatology · doi:10.1002/hep.32689 · Cited by 340
Self-citationIncidence and risk factors of drug‐induced liver injury
Li, X., Tang, J., & Mao, Y. (2022) · Liver International · doi:10.1111/liv.15262 · Cited by 158
Halegoua-DeMarzio, D., Navarro, V., Ahmad, J., Avula, B., Barnhart, H., Barritt, A. S., Bonkovsky, H. L., Fontana, R. J., Ghabril, M. S., Hoofnagle, J. H., et al. (2023) · The American Journal of Medicine · doi:10.1016/j.amjmed.2022.09.026 · Cited by 119
Self-citationEstimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults
Likhitsup, A., Chen, V. L., & Fontana, R. J. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.25822 · Cited by 30
Self-citation
Metadata
- Authors
- Hoofnagle, J. H., Bonkovsky, H. L., Phillips, E. J., Li, Y., Ahmad, J., Barnhart, H., Durazo, F., Fontana, R. J., Gu, J., Khan, I., Kleiner, D. E., Koh, C., Rockey, D. C., Seeff, L. B., Serrano, J., Stolz, A., Tillmann, H. L., Vuppalanchi, R., Navarro, V. J., & for the Drug‐Induced Liver Injury Network
- Affiliations
- 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
- National Cancer Institute,National Institutes of Health (NIH),Bethesda,MD
- Department of Medicine,Vanderbilt University Medical Center,Nashville,TN
- Duke Clinical Research Institute,Duke University,Durham,NC
- Department of Medicine,Icahn School of Medicine at Mount Sinai,New York,NY
- University of California Los Angeles,David Geffen School of Medicine,Los Angeles,CA
- Department of Medicine,University of Michigan School of Medicine,Ann Arbor,MI
- National Center for Natural Products Research,University of Mississippi,University,MI
- The Laboratory of Pathology,National Cancer Institute, NIH,Bethesda,MD
- Liver Diseases Branch,National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),Bethesda,MD
- Digestive Disease Research Center,Medical University of South Carolina,Charleston,SC
- Department of Medicine,Einstein Healthcare Network,Philadelphia,PA
- Department of Medicine,University of Southern California School of Medicine,Los Angeles,CA
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine,East Carolina University,Greenville,NC
- Department of Medicine,Indiana University School of Medicine,Indianapolis,IN
- ORCID
- Vuppalanchi, Raj
- Venue
- Hepatology
- Published
- 2021-05-17
- Volume
- 73
- Issue
- 6
- Pages
- 2484-2493
- ISSN
- 0270-9139
- 1527-3350
- PMC
- PMC8052949
- Cited by
- 98
- References
- 36
- Language
- en
- Licence
- onlinelibrary.wiley.com/termsAndConditions#vor (vor)
- doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.