Herbal Products and the Liver: A Review of Adverse Effects and Mechanisms

Seeff, Leonard B.; Bonkovsky, Herbert L.; Navarro, Victor J.; Wang, Guqi

doi:10.1053/j.gastro.2014.12.004

Cited by 101 publications

(83 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In recent years, there is an increasing evidence of adverse reactions to these products (Menniti-Ippolito et al 2008;Vitalone et al 2011Vitalone et al , 2012Koncic and Tomczyk 2013;Seeff et al 2014). Herbal supplements are prone to induce toxicity firstly because of their complexity and variability.…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity of green tea: an update

2015

View full text Add to dashboard Cite

Green tea (GT), obtained from the leaves of Camellia sinensis (L.) Kuntze (Fam. Theaceae), is largely used for its potential health benefits such as reduction in risk of cardiovascular diseases and weight loss. Nevertheless, it is suspected to induce liver damage. Present work reviews the hepatic adverse reactions associated with GT-based herbal supplements, published by the end of 2008 to March 2015. A systematic research was carried out on PubMed, MedlinePlus, Scopus and Google Scholar databases, without any language restriction. Moreover, some accessible databases on pharmacovigilance or phytovigilance were consulted. The causality assessment was performed using the CIOMS/RUCAM score. Nineteen cases of hepatotoxicity related to the consumption of herbal products containing GT were identified. The hepatic reactions involved mostly women (16/19); the kind of liver damage was generally classified as hepatocellular (16/19). The causality assessment between consumption of herbal preparation and hepatic reaction resulted as probable in eight cases and as possible in eleven cases. In seven cases, patients used preparations containing only GT, while twelve reactions involved patients who took multicomponent preparations (MC). The reactions induced by GT had a generally long latency (179.1 ± 58.95 days), and the outcome was always resolution, with recovery time of 64.6 ± 17.78 days. On the contrary, liver injury associated with MC had a shorter latency (44.7 ± 13.85 days) and was more serious in four cases that required liver transplantation and, when resolution occurred, the recovery time was longer (118.9 ± 38.79). MC preparations contained numerous other components, many of which are suspected to induce liver damage, so it is difficult to ascribe the toxicity to one specific component, e.g., GT. Present data confirm a certain safety concern with GT, even if the number of hepatic reactions reported is low considering the great extent of use of this supplement. The mechanism of GT hepatotoxicity remains unclear, but factors related to the patient are becoming predominant. A major safety concern exists when GT is associated with other ingredients that can interact between them and with GT, enhancing the risk of liver damage. Patients should be discouraged from using herbal or dietary supplements containing complex mixtures and should be encouraged to use herbal and dietary supplement possibly under supervision of healthcare professionals.

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity of green tea: an update

2015

View full text Add to dashboard Cite

show abstract

“…Among the major findings of this Network has been the realization that most idiosyncratic, non-dose related and unpredictable DILI is due to host immune responses to the causative drugs, herbals, or dietary supplements. Another has been that herbals and dietary supplements are becoming more frequent as causes (Navarro et al 2014; Seeff et al 2015). …”

Section: Introductionmentioning

confidence: 99%

Development of a modified lymphocyte transformation test for diagnosing drug-induced liver injury associated with an adaptive immune response

Whritenour

Zong

et al. 2017

Journal of Immunotoxicology

Self Cite

View full text Add to dashboard Cite

Drug induced liver injury (DILI) is a growing problem. Diagnostic methods to differentiate DILI caused by an adaptive immune response from liver injury of other causes or to identify the responsible drug in patients receiving multiple drugs, herbals, and/or dietary supplements (polypharmacy) have not yet been established. The lymphocyte transformation test (LTT) has been proposed as a diagnostic method to determine if a subject with an apparent hypersensitivity reaction has become sensitized to a specific drug. In this test, peripheral blood mononuclear cells (PBMC) collected from a subject are incubated with drug(s) suspected of causing the reaction. Cell proliferation, measured by the incorporation of [3H]-thymidine into new DNA, is considered evidence of a drug-specific immune response. The objectives of the current studies were to: 1) develop and optimize a modified version of the LTT (mLTT) and 2) investigate the feasibility of using the mLTT for diagnosing DILI associated with an adaptive immune response and identifying the responsible drug. PBMC collected from donors with a history of drug hypersensitivity reactions to specific drugs (manifested as skin rash) were used as positive controls for assay optimization. Following optimization, samples collected from 24 subjects enrolled in the U.S. Drug-Induced Liver Injury Network (DILIN) were tested in the mLTT. Using cytokine and granzyme B production as the primary endpoints to demonstrate lymphocyte sensitization to a specific drug, most samples from the DILIN subjects failed to respond. However, robust positive mLTT responses were observed for two of four samples from three DILIN subjects with hepatitis due to isoniazid (INH). We conclude that the mLTT, as performed here on frozen and thawed PBMC, is not a reliable test for diagnosing DILI caused by all drugs, but that it may be useful for confirming the role of the adaptive immune response in DILI ascribed to INH.

show abstract

“…2,4 Indeed, herbs and dietary supplements are a growing cause of liver injury (HILI) worlwide. 6,7 Whereas the first cohort was homogenous owing to specific inclusion of only cases with idiosyncratic liver injury, 3 the second cohort also included acetaminophen cases that allowed separate assessments. 4 The most important new finding of clinical relevance in the DILIN cohort is the observation in a subgroup that the mortality rate from DILI is significantly higher in patients with preexisting liver disease (16% vs 5.2%), 3 which is a long-standing clinical assumption that never had been verified.…”

mentioning

confidence: 99%