Phytomedicine 20 (2013) 1186–1189 Contents lists available at ScienceDirect Phytomedicine jou rn al h om e page: www.elsevier.de/phymed Short communication Is green tea a potential trigger for autoimmune hepatitis? Eugenia Gallo a,1 , Valentina Maggini a,∗,1 , Margherita Berardi b , Alessandra Pugi a , Rosario Notaro b , Giulia Talini b , Giancarlo Vannozzi c , Siro Bagnoli c , Paolo Forte c , Alessandro Mugelli a,d , Vito Annese c , Fabio Firenzuoli a,d , Alfredo Vannacci a,d a University of Florence, Department of Neuroscience, Psychology, Drug Research and Child Health (NeuroFarBa), Center of Molecular Medicine (CIMMBA), Florence, Italy b Cancer Genetics and Gene Transfer Unit, Core Research Laboratory - Istituto Toscano Tumori, AOUC, Florence, Italy c Gastroenterology Unit at the Careggi University Hospital of Florence, Italy d Center for Integrative Medicine, Careggi General Hospital, University of Florence, Italy a r t i c l e i n f o Article history: Received 14 March 2013 Received in revised form 24 May 2013 Accepted 2 July 2013 Keywords: Autoimmune hepatitis Catechin Green tea Single nucleotide polymorphism a b s t r a c t A case of autoimmune liver hepatitis is reported: the onset was triggered by consumption of green tea infusion in a patient taking oral contraceptives and irbesartan. We hypothesize that our patient, carrying genetic variant of hepatic metabolism making her particu- larly susceptible to oxidative stress, developed an abnormal response to a mild toxic insult, afforded by a combination of agents (oral contraceptives + irbesartan + green tea) that normally would not be able to cause damage. Her particular hepatic metabolism further increased the drugs’ concentration, favoring the haptenization of liver proteins, eventually leading to the development of an autoimmune hepatitis. © 2013 Elsevier GmbH. All rights reserved. Introduction Green tea (Camellia sinensis) is a worldwide consumed bever- age, used for almost 50 centuries. Green tea’s popularity recently increased with scientific evidences that demonstrate its ben- eficial health effects, such as reduced risk of cardiovascular and degenerative diseases, likely due to the antioxidant prop- erties of polyphenols. Among them, catechins, and in particular epigallocatechin-3-gallate (EGCG), seem to be the most effective compound in exerting the beneficial effects of green tea (Boehm et al. 2009). Although EGCG has widely demonstrated an antioxi- dant effect and radical scavenging activity, recent data suggest also a pro-oxidant activity (Forester and Lambert 2011). This oxidative effect may also exert some benefit, inducing apoptosis in tumor cells and, at the same time, stimulating endogenous antioxidant systems in normal tissues, potentially exerting protection against Abbreviations: EGCG, epigallocatechin-3-gallate; AIH, autoimmune like hep- atitis; ALT, alanine aminotransferase; GGT, glutamiltransferase; AP, alkaline phosphatase; CYP, cytochrome P450; UGT, UDP glucuronosyltransferase; GST, glutathione S-transferase; MDR, multidrug resistance; MTHFR, methylenetetra- hydrofolate reductase; SULT, sulfotransferase. ∗ Corresponding author at: University of Florence, Department of NeuroFarBa, CIMMBA, Viale Pieraccini 6, 50139, Italy. Tel.: +39 4271522; fax: +39 0554271280. E-mail address: valentina.maggini@unifi.it (V. Maggini). 1 These authors contributed equally to this study. carcinogenic insults (Forester and Lambert 2011). Despite its pos- itive effects and its wide consumption, recently, some reports of suspected green tea-related hepatic reactions have also been pub- lished; those were generally observed in subjects taking high doses of dietary supplements containing concentrated or purified tea preparations, even if one case study reported hepatotoxicity after consumption of 6 cups/day of green tea infusion (Mazzanti et al. 2009). The potential hepatotoxicity of green tea could be related to EGCG-induced oxidative stress with the main evidences suppor- ting an idiosyncratic or immune-mediated mechanism (Lambert et al. 2010). The major risk factors implicated in idiosyncratic drug induced liver injury are old age, female gender, high dose, drug interactions, cross-sensitizations, genetic factors, and hepatic metabolism of the compounds (Czaja 2011). In addition, as it hap- pens with other herbal remedies, green tea molecules may act as triggers for an immune process and may lead to an autoimmune like hepatitis (AIH) according to the ‘hapten hypothesis’ (Czaja 2011). Here we report a case of autoimmune liver hepatitis whose onset was triggered by consumption of green tea infusion in a patient taking oral contraceptives and irbesartan. Case presentation A 42-year-old woman was admitted to the Gastroenterology Unit of Careggi University Hospital of Florence for sudden onset of jaundice, without fever or abdominal pain. Laboratory analyses 0944-7113/$ – see front matter © 2013 Elsevier GmbH. All rights reserved. http://dx.doi.org/10.1016/j.phymed.2013.07.004