Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update.

Drug-induced liver injury (DILI) is an important adverse drug reaction that can lead to acute liver failure or even death in severe cases. Currently, the diagnosis of DILI still follows the strategy of exclusion. Therefore, a detailed history taking and a thorough and careful exclusion of other potential causes of liver injury is the key to correct diagnosis. This guideline was developed based on evidence-based medicine provided by the latest research advances and aims to provide professional guidance to clinicians on how to identify suspected DILI timely and standardize the diagnosis and management in clinical practice. Based on the clinical settings in China, the guideline also specifically focused on DILI in chronic liver disease, drug-induced viral hepatitis reactivation, common causing agents of DILI (herbal and dietary supplements, anti-tuberculosis drugs, and antineoplastic drugs), and signal of DILI in clinical trials and its assessment.

[Interpretation on Consensus on drug-induced liver injury by CIOMS Working Group:liver injury attributed to herbal and dietary supplements].

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.

The use of herbal and dietary supplements for COVID-19 prevention: A survey among the public in a Malaysian suburban town.

Introduction: The spread of the novel coronavirus disease (COVID-19) may lead people to seek preventative measures. The use of herbal and dietary supplements (HDS) may have become prevalent during the COVID-19 pandemic. This study aims to identify the prevalence, predictors, and patterns of HDS use for COVID-19 prevention in a sample of the general public in a suburban town in Malaysia. Methods: An online cross-sectional survey was conducted between May and June 2021 involving adults ≥ 18 years old. Data on the self-reported use of HDS for COVID-19 prevention were collected. Logistic regression analysis was conducted to determine the predictors of HDS use. Results: Overall, 41.9 % (168/401) reported using HDS to prevent COVID-19. Multivariate analysis showed that HDS users were more likely to be individuals ≥ 40 years old (adjusted odds ratio [aOR] = 1.774, 95 % confidence interval [CI] = 1.016 - 3.098), and to have had a history of HDS use prior to the pandemic (aOR = 19.378, 95 % CI = 5.901 - 63.639). Most HDS users referred to social media or websites (66.7 %, 112/168) for HDS information. Approximately half of them had consulted either pharmacists or doctors about their HDS use. Conclusion: HDS use to prevent COVID-19 was common among the respondents. Several issues - such as the concurrent use of HDS with conventional medications, the use of unreliable sources of information, and the lack of consultation with healthcare providers (HCPs) - indicate that HCPs should be more proactive in their consultative and information-providing roles regarding HDS use.

Interpretation on Consensus on drug-induced liver injury by CIOMS Working Group:liver injury attributed to herbal and dietary supplements / 中国中药杂志

With the increase in the medical level, the improvement of adverse drug reaction(ADR) monitoring systems, and the enhancement of public awareness of safe medication, drug safety incidents have been frequently reported. Drug-induced liver injury(DILI), especially liver injury attributed to herbal and dietary supplements(HDS), has globally attracted high attention, bringing great threats and severe challenges to the people for drug safety management such as clinical medication and medical supervision. Consensus on drug-induced liver injury had been published by the Council for International Organizations of Medical Sciences(CIOMS) in 2020. In this consensus, liver injury attributed to HDS was included in a special chapter for the first time. The hot topics, including the definition of HDS-induced liver injury, epidemiological history, potential risk factors, collection of related risk signals, causality assessment, risk prevention, control and management were discussed from a global perspective. Based on the previous works, some experts from China were invited by CIOMS to undertake the compilation of this chapter. Meanwhile, a new causality assessment in DILI based on the integrated evidence chain(iEC) method was widely recognized by experts in China and abroad, and was recommended by this consensus. This paper briefly introduced the main contents, background, and characteristics of the Consensus on drug-induced liver injury. Significantly, a brief interpretation was illustrated to analyze the special highlights of Chapter 8, "Liver injury attributed to HDS", so as to provide practical references for the medical staff and the researchers who worked on either Chinese or Western medicine in China.

Self-Learning about Herbal and Dietary Supplements: Perspectives Using the Theoretical Domains Framework.

Background: Self-learning (SL) is a process in which individuals take the initiative to acquire knowledge with or without the help of others. Knowledge about herbal and dietary supplements (HDS) is important for pharmacists. Unfortunately, there is limited coverage of topics relating to HDS in the pharmacy curricula. The present focus group study applies the Theoretical Domains Framework (TDF) to explore pharmacy students' practices and beliefs regarding SL about HDS (SL-HDS). Methods: Focus group interviews (FGIs) were conducted between April and May 2019 among a sample of undergraduate pharmacy students at a public university (n = 20). Four FGI sessions were conducted, each lasting about 60 to 75 min, and all the sessions were audio-recorded. The interviews were transcribed verbatim and analysed using thematic content analysis. Results: Beliefs about SL-HDS were categorised into 12 domains based on the TDF. Students showed positive attitudes towards SL-HDS and agreed that their involvement in SL-HDS was instrumental in improving their knowledge about various aspects of HDS including indications, adverse effects, and HDS-drug interactions. Various facilitators and barriers influencing students' participation in SL-HDS were uncovered (e.g., access to the internet, time, availability of reference resources). The students demanded to be equipped with critical appraisal skills, as they had limited confidence in assessing literature or information about HDS. Conclusion: This study revealed that the students saw the benefits of SL-HDS. They also perceived that engaging in SL-HDS is compatible with the role of pharmacy students. The findings showed students' readiness and willingness to conduct SL-HDS.

Why Did I Consult My Pharmacist about Herbal and Dietary Supplements? An Online Survey Amid the COVID-19 Pandemic in Malaysia.

Herbal and dietary supplements (HDSs) are frequently obtained from community pharmacies, but community pharmacists (CPs) have been underutilized for information regarding them. This study aimed to determine the prevalence of, factors behind, and reasons for consultation with CPs among HDS consumers in Malaysia. A cross-sectional study using an online survey was conducted among conveniently sampled individuals in Malaysia. Reasons for consultation or non-consultation with CPs about HDSs were sought from the respondents. A logistic regression analysis was conducted to determine the predictors of consultation with CPs. Overall, 40.3% (239/593) of participants consulted CPs about the HDSs that they purchased. The participants were predominantly unmarried (362/588, 61.6%) and belonged to the 18-29 age group (332/593, 56%). The multivariate analysis showed that a suburban residential setting was the only significant predictor for consultation with CPs (adjusted odds ratio = 0.390, 95% CI = 0.260-0.583). Respondents who consulted CPs generally agreed that the CPs were the right people to consult on HDSs (mean = 4.37, SD = 0.73). However, their discussion with CPs regarding HDSs mostly revolved around the benefits and directions for use, but little on the potential risks. Meanwhile, most respondents who did not consult CPs agreed that they had never thought of consulting CPs about their HDS use (mean = 3.45, SD = 1.02). The majority of them referred to the Internet (61.3%, 217/354) and social media (59.9%, 212/354) for information about HDSs. The findings from this study show that more efforts are warranted in encouraging consumers to consult CPs about their HDS use and to enhance their awareness of the roles of CPs in ensuring the safe use of HDSs.

Herbal and Dietary Supplements-Induced Liver Injury in Latin America: Experience From the LATINDILI Network.

BACKGROUND: Herbal and dietary supplements (HDS) consumption, a growing cause of hepatotoxicity, is a common practice among Latin-American populations. OBJECTIVES: To evaluate clinical, laboratory features and outcome in HDS-hepatotoxicity included in the Latin America-Drug Induced Liver Injury (LATINDILI) Network. METHODS: A total of 29 adjudicated cases of HDS hepatotoxicity reported to the LATINDILI Network from October 2011 through December 2019 were compared with 322 DILI cases due to conventional drugs and 16 due to anabolic steroids as well as with other series of HDS-hepatotoxicity. RESULTS: From 367 DILI cases, 8% were attributed to HDS. An increasing trend in HDS-hepatotoxicity was noted over time (p = .04). Camellia sinensis, Herbalife® products, and Garcinia cambogia, mostly used for weight loss, were the most frequently adjudicated causative agents. Mean age was 45 years (66% female). Median time to onset was 31 days. Patients presented typically with hepatocellular injury (83%) and jaundice (66%). Five cases (17%) developed acute liver failure. Compared to conventional medications and anabolic steroids, HDS hepatotoxicity cases had the highest levels of aspartate and alanine transaminase (p = .008 and p = .021, respectively), had more re-exposure events to the culprit HDS (14% vs 3% vs 0%; p = .026), and had more severe and fatal/liver transplantation outcomes (21% vs 12% vs 13%; p = .005). Compared to other DILI cohorts, less HDS hepatotoxicity cases in Latin America were hospitalized (41%). CONCLUSIONS: HDS-hepatotoxicity in Latin-America affects mainly young women, manifests mostly with hepatocellular injury and is associated with higher frequency of accidental re-exposure. HDS hepatotoxicity is more serious with a higher chance of death/liver transplantation than DILI related to conventional drugs.

Drug-Induced Liver Injury from Herbal Liver Detoxification Tea.

The increasing consumption of unregulated herbal and dietary supplements has presented clinicians with new challenges in assessing and managing acute liver injury. Patients may present in various ways ranging from asymptomatic transaminitis to acute liver failure. Several natural products have been found to mitigate drug-induced liver injury, which has led to the creation of numerous registries to outline all its aspects further. We describe the case of a 36-year-old female who developed a clinically significant acute liver injury with a cholestatic pattern due to an over-the-counter herbal liver detox tea. This is the first case reported of a hepatotoxic effect from any of these compounds or ingredients in the detox tea: burdock root, stinging nettle leaf, cleavers herb, dandelion root, lemon peel, and lemon myrtle leaf (Backhousia citriodora). Idiosyncratic drug-induced liver injury (DILI) remains poorly understood; however, recognizing potential toxins is imperative to understanding toxicogenomics and identifying those at risk.

Metabolic Activation of the Toxic Natural Products From Herbal and Dietary Supplements Leading to Toxicities.

Currently, herbal and dietary supplements have been widely applied to prevent and treat various diseases. However, the potential toxicities and adverse reactions of herbal and dietary supplements have been increasingly reported, and have gradually attracted widespread attention from clinical pharmacists and physicians. Metabolic activation of specific natural products from herbal and dietary supplements is mediated by hepatic cytochrome P450 or intestinal bacteria, and generates chemical reactive/toxic metabolites that bind to cellular reduced glutathione or macromolecules, and form reactive metabolites-glutathione/protein/DNA adducts, and these protein/DNA adducts can result in toxicities. The present review focuses on the relation between metabolic activation and toxicities of natural products, and provides updated, comprehensive and critical comment on the toxic mechanisms of reactive metabolites. The key inductive role of metabolic activation in toxicity is highlighted, and frequently toxic functional groups of toxic natural products were summarized. The biotransformation of drug cytochrome P450 or intestinal bacteria involved in metabolic activation were clarified, the reactive metabolites-protein adducts were selected as biomarkers for predicting toxicity. And finally, further perspectives between metabolic activation and toxicities of natural products from herbal and dietary supplements are discussed, to provide a reference for the reasonable and safe usage of herbal and dietary supplements.

Herbal and dietary supplement-induced liver injury in Taiwan: comparison with conventional drug-induced liver injury.

BACKGROUND AND AIMS: Whether herbal and dietary supplements (HDS) are safer than Western conventional drugs is controversial. The aim of this study was to explore the characteristics and risk factors for HDS-induced liver injury (HILI) in Taiwan. METHODS: This is a 9-year multi-center prospective study conducted in Taiwan from 2011 to 2019. Patients with HILI were compared to those with conventional drug-induced liver injury (CILI). RESULTS: A total of 1,297 patients were enrolled, of whom 285 (22.0%) had HILI and 1,012 (78.0%) had CILI. Compared to the CILI group, the HILI group had higher initial serum alanine aminotransferase, alkaline phosphatase (ALP), peak ALP and bilirubin levels, and higher rates of jaundice, ascites, encephalopathy, coagulopathy, sepsis and acute liver failure. In addition, the HILI group had a higher mortality rate than the CILI group (12.6 vs. 8.0%, p = 0.016). Hepatitis B carrier status, elevated baseline liver biochemical tests and the use of crude herbs (without processing) were associated with an increased risk of HILI-related mortality (adjusted hazard ratios [95% confidence intervals]: 2.90 [1.43-5.99], 2.40 [1.01-5.68] and 2.94 [1.45-5.97], respectively). CONCLUSIONS: HDS are popular and incriminated in more than one-fifth of drug-induced liver injuries in Taiwan. The patients with HILI were more severe than those with CILI in terms of liver biochemical tests, complications and mortality. Hepatitis B carriers, those with elevated baseline liver tests and crude herb users may have a higher risk of HILI-related mortality. The prudent use of HDS is suggested in these high-risk subjects.

Screening of hepatotoxic compounds in Psoralea corylifolia L., a traditional Chinese herbal and dietary supplement, using high-resolution mass spectrometry and high-content imaging.

Owing to the complexity of the composition of herbal and dietary supplements, it is a challenging problem to efficiently screen and identify active or toxic compounds. Psoralea corylifolia L. (PCL) was selected as the subbject to establish a methodology for rapid screening and identification of hepatotoxic compounds. High-content imaging, ultra-performance liquid chromatography and high-resolution mass spectrometry were used in this study to detect the hepatotoxicity and identify unknown compounds in PCL samples. Then, putative toxic compounds which are highly related to hepatotoxicity were screened by spectrum-toxicity correlation analysis, and the toxicity intensity verified by high-content imaging. The maximum nontoxic dose of processed samples with good detoxification effect reduced more than 9 times compared with unprocessed raw medicinal materials. Spectrum-toxicity correlation analysis showed that bavachinin A, bavachin, isobavachalcone and neobavaisoflavone had high correlation with the hepatotoxicity of PCL, and psoralen and isopsoralen had low correlation with hepatotoxicity. This study verified the hepatotoxicity of these six putative compound monomers, proving the results of spectrum-toxicity correlation analysis. Based on the correlation analysis of high-resolution mass spectrometry of detection compounds and high-content imaging of hepatocyte toxicity data, the potential toxic compound of herbal and dietary supplement products can be quickly and accurately screened.

Profile of herbal and dietary supplements induced liver injury in Latin America: A systematic review of published reports.

Hepatotoxicity related to HDS is a growing global health issue. We have undertaken a systematic review of published case reports and case series from LA from 1976 to 2020 to describe the clinical features of HDS related hepatotoxicity in this region. We search in PubMed, Web of Science, Scopus and specific LA databases according to PRISMA guidelines. Only HILI cases published in LA that met criteria for DILI definition were included. Duplicate records or reports that lacked relevant data that precluded establishing causality were excluded. Finally, 17 records (23 cases) were included in this review. Centella asiatica, Carthamus tinctorius, and Herbalife® were the most reported HDS culprit products, the main reason for HDS consumption was weight loss. The clinical characteristics of HDS hepatotoxicity in our study were compared to those of other studies in the USA, Europe and China showing a similar signature with predominance of young females, hepatocellular damage, a high rate of ALF and mortality, more frequent inadvertent re-challenge and chronic damage. This study underscores the challenge in causality assessment when multi-ingredients HDS are taken and the need for consistent publication practice when reporting hepatotoxicity cases due to HDS, to foster HDS liver safety particularly in LA.

Integrative medicine smart phrase pilot study: Evaluating an EHR tool to improve providers' attitudes, knowledge and use of herbal and dietary supplements.

CONTEXT: While many patients use herbal and dietary supplements (H/DS) for wellness, disease prevention and treatment, providers still cite a lack of resources and formal training as barriers to responding to patients' inquiries about H/DS. Although the federal government, academic institutions and the private sector now offer more opportunities for education and research on H/DS, greater support in real time is needed to facilitate providers during the clinical encounter. OBJECTIVE: This small, pilot study evaluates the effects of implementation of smart phrases in the electronic health record (EHR) and an educational intervention on providers' knowledge, attitude and use of H/DS in the clinical encounter. DESIGN, SETTING AND PARTICIPANTS: The study was conducted at The Institute for Family Health (IFH), a Federally Qualified Health Center and academic health center which operates the Department of Family Medicine and Community Health in affiliation with the Icahn School of Medicine at Mount Sinai. Baseline and post-intervention surveys were conducted to explore providers' attitudes, knowledge and use of integrative medicine (IM) smart phrases on H/DS. MAIN OUTCOME MEASURES: Providers' awareness of smart phrases of H/DS, knowledge of the content, confidence in using smart phrases to discuss H/DS, self-reported use of smart phrases were measured. RESULTS: A total of 32 subjects participated in the intervention and completed the baseline survey. Only half of the participants were familiar with the IM smart phrases in our system and 12.5% felt they were aware of the information covered in these smart phrases. Eighteen of 32 participants completed the post-intervention assessment. The intervention was successful in statistically increasing participants' self-reported awareness of the information covered in the IM smart phrases (p<0.01). Increased confidence in using IM smart phrases to initiate patients on a new supplement showed statistical significance (p=0.03). There were no clear patterns in reported behavior changes following the training with the exception of a significant increase in the self-reported frequency of past month use of IM smart phrases during a patient visit (p=0.01). Lastly, there were no changes in the frequency of smart phrase use in the EHR. CONCLUSION: The implementation and adoption of evidence-based use of H/DS in the clinical encounter requires a sustained educational component to make the availability of smart phrases via technology (EHR) an effective strategy.

Monocyte-Derived Hepatocyte-Like Cell Test: A Novel Tool for in vitro Identification of Drug-Induced Liver Injury in Patients with Herbal or Dietary Supplements.

BACKGROUND: Drug-induced liver injury caused by herbal and dietary supplements (HDS) has been an increasingly important phenomenon in recent years. Diagnosis is the major challenge. Definite causality assessment, especially in patients with concomitant prescription medicine or other potential causes of liver injury, can be impossible. OBJECTIVES: We investigated the usefulness of an in vitro test on the basis of peripheral monocytes of the individual patients in patients with acute liver injury consuming HDS. METHOD: Patients with acute liver injury who had been prospectively recruited by the University Hospital Munich (LMU, Munich) and the Chinese University of Hong Kong (CUHK) and who took at least 1 HDS were selected for this analysis. Diagnosis of drug-induced liver injury (DILI) was based on local expert adjudication, Roussel Uclaf Causality Assessment Method (RUCAM) score, and course of the disease and was supported by the monocyte-derived hepatocyte-like (MH) cell test. RESULTS: We identified 47 patients with liver injury and intake of at least 1 HDS: 32 (68%) were diagnosed with DILI. HDS was determined as the causative agent in 28 out of those 32 patients. The MH cell test could correctly identify 29 out of those 32 DILI cases and showed false positive results in only 2 out of the 15 non-DILI patients. The MH cell test therefore reached a sensitivity and specificity of 90.6 and 86.7%, respectively, in patients with acute liver injury and HDS intake. CONCLUSIONS: Our data provide evidence that the MH cell test can be a useful tool to identify the role of HDS in causing DILI and therefore support causality assessment in patients consuming HDS.

Epigallocatechin Gallate During Dietary Restriction - Potential Mechanisms of Enhanced Liver Injury.

Green tea extract (GTE) is popular in weight loss, and epigallocatechin gallate (EGCG) is considered as the main active component. However, GTE is the primary cause of herbal and dietary supplement-induced liver injury in the United States. Whether there is a greater risk of liver injury when EGCG is consumed during dieting for weight loss has not been previously reported. This study found for the first time that EGCG could induce enhanced lipid metabolism pathways, suggesting that EGCG had the so-called "fat burning" effect, although EGCG did not cause liver injury at doses of 400 or 800 mg/kg in normal mice. Intriguingly, we found that EGCG caused dose-dependent hepatotoxicity on mice under dietary restriction, suggesting the potential combination effects of dietary restriction and EGCG. The combination effect between EGCG and dietary restriction led to overactivation of linoleic acid and arachidonic acid oxidation pathways, significantly increasing the accumulation of pro-inflammatory lipid metabolites and thus mediating liver injury. We also found that the disruption of Lands' cycle and sphingomyelin-ceramides cycle and the high expression of taurine-conjugated bile acids were important metabolomic characteristics in EGCG-induced liver injury under dietary restriction. This original discovery suggests that people should not go on a diet while consuming EGCG for weight loss; otherwise the risk of liver injury will be significantly increased. This discovery provides new evidence for understanding the "drug-host" interaction hypothesis of drug hepatotoxicity and provides experimental reference for clinical safe use of green tea-related dietary supplements.

Development and validation of novel scales to determine pharmacist's care for herbal and dietary supplement users.

BACKGROUND: The factors associated with the provision of pharmacist's care (PCare) for herbal and dietary supplement (HDS) users are multidimensional. These factors should be investigated to assess the needs for community pharmacists (CPs) to provide the service. However, at present, there are no validated and reliable theory-based instruments to measure the factors. OBJECTIVES: The study aims to develop and validate scales (direct and indirect) based on a modified Theory of Planned Behavior (TPB) to measure factors associated with the provision of PCare for HDS users by Thai CPs. METHOD: Item generation for the scales was based on the theoretical constructs of the modified TPB framework, literature review, and authors' previous qualitative study. Draft items were then subjected to content validity and face validity. Psychometric testing was carried out among CPs in Bangkok, Thailand. Refinement of the scales utilized factor analysis and validity was assessed using factor analysis and Rasch analysis. Internal consistency reliability and construct reliability were used to assess the scales' reliability. RESULTS: Initially, the direct and indirect scales contained 15 and 28 items, respectively and were reduced to 12 and 16 items, after experts' review. Factor analysis further reduced the number of items of the indirect scale to 13. For both scales, confirmatory factor analysis showed model-data fit. Each construct of the direct scale was significant predictors of intention. Moreover, each construct of the direct scale correlated positively and significantly with the respective construct of the indirect scale, signifying concurrent validity. No misfit item was identified in the Rasch analysis and the majority of items were invariant across gender. Internal consistency reliability and construct reliability of the scales were acceptable. CONCLUSION: This study presents the development and validation of theoretically-grounded scales to measure the factors associated with the provision of PCare for HDS users by Thai CPs.

The landscape of hepatobiliary adverse reactions across 53 herbal and dietary supplements reveals immune-mediated injury as a common cause of hepatitis.

Recent evidence suggests herbal-induced liver injury (HILI) to account for 20% of cases among the U.S. Drug-Induced-Liver-Injury-Network. To define injury patterns of HILI, we reviewed the clinical data of 413 patients exposed to 53 HDS products by considering the evidence for HILI and its grades of severity. Outstandingly, females developed HILI more rapidly (p = 0.018) and the time to recovery was significantly increased (p = 0.0153). > 90% of reported cases were severe and half of HDS products caused acute liver failure (ALF) requiring liver transplantation or resulted in fatal outcomes. Liver biopsies of 243 patients defined 13 histological features; two-thirds of products elicited immune-mediated hepatitis and included 154 Hy's law positive cases. The histological injury patterns were confirmed among unrelated patients, while accidental re-challenges evidenced culprits as causative. Furthermore, one-fifth of patients presented elevated autoantibody titres indicative of autoimmune-like HILI, and one-third of the products were linked to chronic hepatitis and cholestatic injuries not resolving within 6 months. Lastly, INR and TBL are critical laboratory parameters to predict progression of severe HILI to ALF. Our study highlights the need for a regulatory framework to minimize the risk for HILI. Better education of the public and a physician-supervised self-medication plan will be important measures to abate risk of HILI.

Severe liver injury due to herbal and dietary supplements and the role of liver transplantation.

Herbal and dietary supplements (HDS) are increasingly used worldwide for numerous, mainly unproven health benefits. The HDS industry is poorly regulated compared to prescription medicines and most products are easily obtainable. Drug induced liver injury (DILI) is a well-recognized entity associated with prescription and over the counter medications and many reports have emerged of potential HDS-related DILI. There is considerable geographic variability in the risk and severity of DILI associated with HDS but the presentation of severe liver injury is similar with a hepatocellular pattern accompanied by jaundice. This type of injury can lead to acute liver failure and the need for liver transplantation. Patients will often fail to mention their use of HDS, considering it natural and therefore harmless. Hence physicians should understand that these products can be associated with DILI and explicitly ask about HDS use in any patient with otherwise unexplained acute liver injury.