Short communicationIs green tea a potential trigger for autoimmune hepatitis?
Introduction
Green tea (Camellia sinensis) is a worldwide consumed beverage, used for almost 50 centuries. Green tea's popularity recently increased with scientific evidences that demonstrate its beneficial health effects, such as reduced risk of cardiovascular and degenerative diseases, likely due to the antioxidant properties 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 antioxidant 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 carcinogenic insults (Forester and Lambert 2011). Despite its positive effects and its wide consumption, recently, some reports of suspected green tea-related hepatic reactions have also been published; 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 supporting 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 happens 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.
Section snippets
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 revealed total bilirubin level 31 mg/dl, direct bilirubin 21 mg/dl, aspartate aminotransferase 1447 U/l; alanine aminotransferase (ALT), 1618 U/l, γ glutamiltransferase (GGT) 158 UI/l, alkaline phosphatase (AP) 115 U/l, γ-globulin 20%. An extensive diagnostic workup discarded any other known etiology for liver
Discussion
Since the patient presented with an acute liver damage, our first diagnostic hypothesis was an acute toxic hepatitis. This was also compatible with the histological findings at liver biopsy. Nevertheless, since the clinical features of the patient markedly improved after steroid treatment and worsened again after steroid withdrawal, a diagnosis of autoimmune hepatitis, triggered by an acute toxic damage, was finally performed.
The patient was taking since a long time irbesartan and a combination
Conclusions
With respect to the drugs assumed by the patient, estrogen and irbesartan were associated to the onset of hepatic injury also autoimmune-like type (Navarro and Senior 2006). On the other hand irbesartan and oral contraceptives were well tolerated by the patient for several years, suggesting that they were not sufficient to cause AIH.
Most drug-induced liver injuries have an acute onset and manifest histological patterns that can be categorized as hepatocellular, cholestatic, or mixed.
Funding
This work is supported by a grant from the Italian Ministry of Health (“Progetto Giovani Ricercatori” 2007).
Conflict of interest
None.
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United States Pharmacopeia (USP) comprehensive review of the hepatotoxicity of green tea extracts
2020, Toxicology ReportsCitation Excerpt :To eliminate the possible effects of other ingredients in the involved products, only cases associated with products containing GTE as a single ingredient (35 cases out of 75 cases) were analyzed to determine the causal relationship between the product and hepatotoxicity. Of the 51 published reports of liver injury associated with intake of products containing GTE found during the literature search, [5–7,12,128–156]; fifteen articles describing 20 cases were reported in a non-English language and were translated to English by co-authors and then analyzed [42,43,45,157–169]. All case reports were categorized into two groups; those associated with single ingredient dietary supplements (SIDS) (N = 35) and those associated with multiple ingredient dietary supplements (MIDS) (N = 40).
Bioactive nutrients - Time for tolerable upper intake levels to address safety
2017, Regulatory Toxicology and PharmacologyCitation Excerpt :Given the limitations of the Kim et al. study (small sample size, short duration), and the absence of liver adverse effects below 600 mg/day, an uncertainty factor (UF) of 2 was selected, resulting in a proposed EGCG UL of 300 mg/day based on human intervention data. A total of 22 published case reports involving green tea and liver injury were identified in PubMed (Abu el Wafa et al., 2005; Amariles et al., 2009; Bergman and Schjøtt, 2009; Bonkovsky, 2006; Chen et al., 2010; Federico et al., 2007; Gallo et al., 2013; Gloro et al., 2005; Javaid and Bonkovsky, 2006; Jimenez-Saenz and Martinez-Sanchez, 2006; Jiménez-Encarnación et al., 2012; Lugg et al., 2015; Manso et al., 2011; Martínez-Sierra et al., 2006; Mazzanti et al., 2009; Molinari et al., 2006; Patel et al., 2013; Pillukat et al., 2014; Rohde et al., 2011; Vanstraelen et al., 2008; Verhelst et al., 2009; Yellapu et al., 2011). The post market surveillance (adverse event) data set included cases from 2006 to date (10 years) from the FDA, Health Canada, TGA, and WHO databases (FAERS, 2016; Health Canada, 2015; DAEN, 2016; WHO, 2016).
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These authors contributed equally to this study.