ABSTRACT
Title
Acute Hepatitis associated with use of green tea and oral contraceptives: a case report
Authors
1E. Gallo,1A. Pugi, 1V. Maggini,1G. Pieraccini, 2R. Notaro,1L. Longo, 3V. Annese,3G. Vannozzi, 1,4F. Firenzuoli, 1,4A. Mugelli,1,4A. Vannacci
1 University of Florence, Department of Pharmacology, CIMMBA, Florence
2 Istituto Toscano Tumori, ITT, Firenze, Italy
3 Gastroenterology Unit at the Careggi University Hospital Of Florence
4 Centre for Integrative Medicine, Careggi General Hospital, University of Florence
1 University of Florence, Department of Pharmacology, CIMMBA, Florence
2 Istituto Toscano Tumori, ITT, Firenze, Italy
3 Gastroenterology Unit at the Careggi University Hospital Of Florence
4 Centre for Integrative Medicine, Careggi General Hospital, University of Florence
Abstract
Green tea (Camellia sinensis) is one of the most consumed beverages in the world, especially in Asian countries. Historically, green tea has been lauded for various beneficial health effects, and more recently its biological activities have been investigated. Some studies have shown that green tea consumption is associated with a reduced risk of cardiovascular diseases, degenerative diseases, and cancer [Boehm K et al, 2009]. The potential health benefits associated with green tea consumption have been partially attributed to the antioxidative properties of polyphenols, particularly to catechins, among which Epigallocatechin-3-gallate(EGCG) is the most effective. Unfortunately, some reports of adverse effects, mainly hepatitis, associated to the consumption of green tea preparations (extract or infusion) have been published [Mazzanti et al2009]. Since then, much attention has been given to the possible hepatotoxic effects of green tea. Here, we report a case of acute liver dysfunction caused by consumption of green tea infusion in a patient taking oral contraceptives (ethinylestradiol, gestodene).
Case presentation
A 42-year-old woman with jaundice was admitted to the Gastroenterology Unit of Careggi University Hospital of Florence. Laboratory analysis revealed total bilirubin level 31 mg/dL,direct bilirubin 21mg/dL,aspartate aminotransferase, 1447 U/L; alanine aminotransferase, 1618 U/L and a liver biopsy showed hepatocellular necrosis and mixed inflammatory infiltrate. An extensive diagnostic workup discarded any other known etiology for her liver disease. Viral serology for active hepatitis A,B,C, and extensive toxicology screening were all negative. A detailed history revealed that the patient had been drinking Japanese matcha green tea (micronized water-soluble powder of Camellia sinensis) every other day for 10 days. Green tea was withdrawn and liver functions tests normalized within some months.
Discussion
Although tea beverages have been consumed for almost 50 centuries, the co-assumption ofgreen tea and oral contraceptive needs to be considered potentially hepatotoxic since being involved in some cases of toxic hepatitis[Mazzanti et al,2009; Navarro et al, 2006 ]. The mechanism of toxicity of green tea is unclear, the possibility of idiosyncratic, or immune-mediated mechanism, was suggested. Given the relative rarity of the reaction it seems likely that host genetic factors could been important in modulating patient susceptibility to herb-drug interaction. In vitro and in vivo animal experiments and clinical trials have shown some evidence of a green tea interaction with the CYP3A4 activity [Colalto C 2010]. CYP3A4 mediated also the oxidative metabolism of the oral contraceptive [Zhang, 2007].
A possible explanation may be that green tea (EGCG) inhibits the metabolic degradation via CYP3A4 of oral contraceptives with consequent increased bioavailability and relative toxicity.
This case report could confirm that green tea, even conventional infusions, may induce severe acute mixed liver injury in predisposed individuals. A possible pharmacogenetic predisposition (e.g. green tea/oral contraceptive interaction) as well as possible contaminations during the growth of the leaves or during productionof the product were investigated with appropriate techniques. Results of these investigations will be reported in the present communication.
References
Boehm K et al, 2009, Cochrane Database Syst Rev. 2009 Jul 8;(3):CD005004.
Colalto C. 2010 Pharmacol Res. Sep;62(3):207-27.
Mazzanti G, et al 2009 Eur J Clin Pharmacol. Apr;65(4):331-41
Navarro VJ, et al 2006 N Engl J Med. Feb 16;354(7):731-9.
Zhang H et al 2007 Clin Pharmacokinet.;46(2):133-57.
Case presentation
A 42-year-old woman with jaundice was admitted to the Gastroenterology Unit of Careggi University Hospital of Florence. Laboratory analysis revealed total bilirubin level 31 mg/dL,direct bilirubin 21mg/dL,aspartate aminotransferase, 1447 U/L; alanine aminotransferase, 1618 U/L and a liver biopsy showed hepatocellular necrosis and mixed inflammatory infiltrate. An extensive diagnostic workup discarded any other known etiology for her liver disease. Viral serology for active hepatitis A,B,C, and extensive toxicology screening were all negative. A detailed history revealed that the patient had been drinking Japanese matcha green tea (micronized water-soluble powder of Camellia sinensis) every other day for 10 days. Green tea was withdrawn and liver functions tests normalized within some months.
Discussion
Although tea beverages have been consumed for almost 50 centuries, the co-assumption ofgreen tea and oral contraceptive needs to be considered potentially hepatotoxic since being involved in some cases of toxic hepatitis[Mazzanti et al,2009; Navarro et al, 2006 ]. The mechanism of toxicity of green tea is unclear, the possibility of idiosyncratic, or immune-mediated mechanism, was suggested. Given the relative rarity of the reaction it seems likely that host genetic factors could been important in modulating patient susceptibility to herb-drug interaction. In vitro and in vivo animal experiments and clinical trials have shown some evidence of a green tea interaction with the CYP3A4 activity [Colalto C 2010]. CYP3A4 mediated also the oxidative metabolism of the oral contraceptive [Zhang, 2007].
A possible explanation may be that green tea (EGCG) inhibits the metabolic degradation via CYP3A4 of oral contraceptives with consequent increased bioavailability and relative toxicity.
This case report could confirm that green tea, even conventional infusions, may induce severe acute mixed liver injury in predisposed individuals. A possible pharmacogenetic predisposition (e.g. green tea/oral contraceptive interaction) as well as possible contaminations during the growth of the leaves or during productionof the product were investigated with appropriate techniques. Results of these investigations will be reported in the present communication.
References
Boehm K et al, 2009, Cochrane Database Syst Rev. 2009 Jul 8;(3):CD005004.
Colalto C. 2010 Pharmacol Res. Sep;62(3):207-27.
Mazzanti G, et al 2009 Eur J Clin Pharmacol. Apr;65(4):331-41
Navarro VJ, et al 2006 N Engl J Med. Feb 16;354(7):731-9.
Zhang H et al 2007 Clin Pharmacokinet.;46(2):133-57.