PMID- 32892374 OWN - NLM STAT- MEDLINE DCOM- 20220107 LR - 20220107 IS - 1527-3350 (Electronic) IS - 0270-9139 (Print) IS - 0270-9139 (Linking) VI - 73 IP - 6 DP - 2021 Jun TI - HLA-B*35:01 and Green Tea-Induced Liver Injury. PG - 2484-2493 LID - 10.1002/hep.31538 [doi] AB - 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. CI - (c) 2020 by the American Association for the Study of Liver Diseases. FAU - Hoofnagle, Jay H AU - Hoofnagle JH AD - 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. FAU - Bonkovsky, Herbert L AU - Bonkovsky HL AD - National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD. AD - Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC. FAU - Phillips, Elizabeth J AU - Phillips EJ AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. FAU - Li, Yi-Ju AU - Li YJ AD - Duke Clinical Research Institute, Duke University, Durham, NC. FAU - Ahmad, Jawad AU - Ahmad J AD - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. FAU - Barnhart, Huiman AU - Barnhart H AD - Duke Clinical Research Institute, Duke University, Durham, NC. FAU - Durazo, Francisco AU - Durazo F AD - University of California Los Angeles, David Geffen School of Medicine, Los Angeles, CA. FAU - Fontana, Robert J AU - Fontana RJ AD - Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI. FAU - Gu, Jiezhun AU - Gu J AD - Duke Clinical Research Institute, Duke University, Durham, NC. FAU - Khan, Ikhlas AU - Khan I AD - National Center for Natural Products Research, University of Mississippi, University, MI. FAU - Kleiner, David E AU - Kleiner DE AD - The Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD. FAU - Koh, Christopher AU - Koh C AD - Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, MD. FAU - Rockey, Don C AU - Rockey DC AD - Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC. FAU - Seeff, Leonard B AU - Seeff LB AD - Department of Medicine, Einstein Healthcare Network, Philadelphia, PA. FAU - Serrano, Jose AU - Serrano J AD - 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. FAU - Stolz, Andrew AU - Stolz A AD - Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA. FAU - Tillmann, Hans L AU - Tillmann HL AD - Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, East Carolina University, Greenville, NC. FAU - Vuppalanchi, Raj AU - Vuppalanchi R AUID- ORCID: 0000-0003-0637-1577 AD - Department of Medicine, Indiana University School of Medicine, Indianapolis, IN. FAU - Navarro, Victor J AU - Navarro VJ AD - Department of Medicine, Einstein Healthcare Network, Philadelphia, PA. CN - Drug-Induced Liver Injury Network LA - eng GR - P30 DK123704/DK/NIDDK NIH HHS/United States GR - U24 DK065176/DK/NIDDK NIH HHS/United States GR - U01 DK083020/DK/NIDDK NIH HHS/United States GR - P20 GM130457/GM/NIGMS NIH HHS/United States GR - U01 DK065184/DK/NIDDK NIH HHS/United States GR - U01 DK065211/DK/NIDDK NIH HHS/United States GR - U01 DK083027/DK/NIDDK NIH HHS/United States GR - U01 DK065201/DK/NIDDK NIH HHS/United States GR - U01 DK100928/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural DEP - 20210517 PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 RN - 0 (HLA-B Antigens) RN - 0 (Tea) RN - EC 2.6.1.- (Transaminases) SB - IM MH - Adult MH - Causality MH - *Chemical and Drug Induced Liver Injury/epidemiology/etiology/immunology/therapy MH - Dietary Supplements/*adverse effects MH - Drug-Related Side Effects and Adverse Reactions/*epidemiology MH - Female MH - HLA-B Antigens/*analysis MH - Humans MH - Incidence MH - Liver Function Tests/methods/statistics & numerical data MH - Liver Transplantation/statistics & numerical data MH - Male MH - Prospective Studies MH - Severity of Illness Index MH - *Tea/adverse effects/immunology MH - Transaminases/blood MH - United States/epidemiology PMC - PMC8052949 MID - NIHMS1681562 EDAT- 2020/09/07 06:00 MHDA- 2022/01/08 06:00 PMCR- 2021/06/22 CRDT- 2020/09/06 20:37 PHST- 2020/07/25 00:00 [revised] PHST- 2020/06/04 00:00 [received] PHST- 2020/08/16 00:00 [accepted] PHST- 2020/09/07 06:00 [pubmed] PHST- 2022/01/08 06:00 [medline] PHST- 2020/09/06 20:37 [entrez] PHST- 2021/06/22 00:00 [pmc-release] AID - 10.1002/hep.31538 [doi] PST - ppublish SO - Hepatology. 2021 Jun;73(6):2484-2493. doi: 10.1002/hep.31538. Epub 2021 May 17.