Herbal And Dietary Supplements Research Articles

Investigation of the Role of Chemical Analysis in Causality Assessment of Herbal and Dietary Supplement-Induced Liver Injury.

The attribution of drug-induced liver injury (DILI) to specific herbal and dietary supplements (HDS) is confounded by inaccurate labels and undisclosed ingredients. The US Drug-Induced Liver Injury Network (DILIN) determines the attribution of injury to an agent through its structured expert opinion causality assessment process, but without the use of chemical analysis data of HDS. We aimed to determine the impact of chemical analysis of HDS products on prior causality assessment scores. Obtained samples of HDS consumed by DILIN-enrolled patients were analyzed by high-performance liquid chromatography-mass spectrometry (HPLC-MS). Chemical analysis data were compared to label accuracy and detect whether the product contained botanical and non-botanical compounds. A comparison of the causality scores reassessed with chemical analysis was compared with the original scores. A total of 54 previously adjudicated cases with chemical analysis available were reassessed for causality with chemical analysis data; reviewers were blinded to original causality scores. Using the chemical analysis data, 37% (n = 20) of the 54 cases were scored with a higher likelihood of DILI compared with the original causality scores; 14 of the 20 (70%) moved from probable to highly likely; 52% had no change in causality score; and 11% of cases were scored as a lower likelihood of DILI. Our study demonstrates that there is value in using HDS chemical analysis data in the causality assessment process for DILI. In more than a third of cases, chemical analysis of products led to an increased confidence in DILI attribution to HDS. These findings suggest that chemical analysis is an important tool in causality assessment for HDS agents, specifically in challenging situations, and further studies are needed to confirm its applicability in clinical practice.

Challenges in herbal-induced liver injury identification and prevention.

Herbal and dietary supplements (HDS) are being used worldwide at an increasing rate. Mirroring this trend, HDS-induced liver injury, also known as HDS-induced liver injury (HILI), has increased significantly over the past three decades in the Drug-Induced Liver Injury Network (DILIN), now accounting for 20% of cases of drug-induced liver injury (DILI). There are significant challenges in the identification and prevention of HILI due to varying presentations, ability to make clear diagnosis, identification of the responsible ingredient, lack of treatment, and lack of regulatory oversight of HDS products to confirm their ingredients and ensure safety. The major implicated agents include anabolic steroids, green tea extract, garcinia cambogia, kratom, ashwagandha, turmeric and multi-ingredient nutritional supplements. Fortunately, with the formation of major DILI consortiums across the world, the last decade has seen advances in the identification of at-risk genetic phenotypes, the use of chemical analysis on multi-ingredient nutritional supplements, and the publication of data/injury patterns of potentially risky HDS.

Estimated Exposure to 6 Potentially Hepatotoxic Botanicals in US Adults

Use of herbal and dietary supplements (HDSs) accounts for an increasing proportion of drug hepatotoxicity cases. Turmeric or curcumin, green tea extract, Garcinia cambogia, black cohosh, red yeast rice, and ashwagandha are the most frequently reported hepatoxic botanicals, but their prevalence and reasons for use in the general population are unknown. To assess the prevalence and clinical characteristics of adult consumers of 6 potentially hepatoxic botanicals. This survey study analyzed nationally representative data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative, cross-sectional survey of the general US population. Prescription drug and HDS exposure data in the past 30 days were analyzed, and 2020 US Census data were used for population estimates. Data were analyzed July 1, 2023, to February 1, 2024. Adult NHANES participants enrolled between January 2017 and March 2020. Baseline weighted characteristics of HDS users and users of 6 potentially hepatotoxic botanical products were compared with non-HDS users. Multivariable analysis was undertaken to identify factors associated with HDS use or at-risk botanical use. Among 9685 adults enrolled in this NHANES cohort, the mean (SE) age was 47.5 (0.5) years, and 51.8% (95% CI, 50.2%-53.4%) were female. The overall prevalence of HDS product use was 57.6% (95% CI, 55.9%-59.4%), while the prevalence of using the 6 botanicals of interest was 4.7% (95% CI, 3.9%-5.7%). Turmeric-containing botanicals were most commonly used (n = 236), followed by products containing green tea (n = 92), ashwagandha (n = 28), Garcinia cambogia (n = 20), red yeast rice (n = 20), and black cohosh (n = 19). Consumers of these 6 botanicals were significantly older (adjusted odds ratio [AOR], 2.36 [95% CI, 1.06-5.25]; P = .04 for 40-59 years of age and AOR, 3.96 [95% CI, 1.93-8.11]; P = .001 for ≥60 years of age), had a higher educational level (AOR, 4.78 [95% CI, 2.62-8.75]; P < .001), and were more likely to have arthritis (AOR, 2.27 [95% CI, 1.62-3.29]; P < .001) compared with non-HDS users. An estimated 15 584 599 (95% CI, 13 047 571-18 648 801) US adults used at least 1 of the 6 botanical products within the past 30 days, which was similar to the estimated number of patients prescribed potentially hepatotoxic drugs, including simvastatin (14 036 024 [95% CI, 11 202 460-17 594 452]) and nonsteroidal anti-inflammatory drugs (14 793 837 [95% CI, 13 014 623-16 671 897]). The most common reason for consuming turmeric and green tea was to improve or maintain health. In this survey study, an estimated 15.6 million US adults consumed at least 1 botanical product with liver liability within the past 30 days, comparable with the number of people who consumed nonsteroidal anti-inflammatory drugs and a commonly prescribed hypolipidemic drug. Given a lack of regulatory oversight on the manufacturing and testing of botanical products, clinicians should be aware of possible adverse events from consumption of these largely unregulated products.

Turmeric-Induced Liver Injury in a Patient with Concurrent Semaglutide Use

Turmeric has surged in popularity as one of the most widely used dietary supplements in the United States. Recognized for its antiinflammatory and antioxidant properties, it has traditionally been regarded as safe. Recent literature and reports in LiverTox have documented over a dozen cases of acute liver injury associated with the use of turmeric supplements. However, potential drug interactions with turmeric have been described but not well-documented. Thus, we present a case of drug-induced liver injury (DILI) correlated with turmeric supplement use and the concurrent use of semaglutide. INTRODUCTION Drug-induced liver injury (DILI) from herbal and dietary supplements (HDS) in the United States has increased as the usage of HDS has become more popular. According to the United States Drug-Induced Liver Injury Network (DILIN), approximately 20% of cases of DILI can be attributed to HDS, an increase from 7% in 2004.1 Turmeric supplements have become one of the top selling HDS in the United States. It is promoted for arthritis, pain, and digestive disorders. Common side effects include dermatitis and gastrointestinal upset, while instances of hepatotoxicity are rare. Different formulations that increase the bioavailability of curcumin, the active ingredient in turmeric, have been linked to cases of liver injury and acute hepatitis outbreaks outside of the United States.2 Possible interactions between turmeric and other drugs, such as anticoagulants, antiplatelets, antidiabetics, and chemotherapeutic agents, have been described in in vitro and animal studies, but have not been well studied in humans.3 In this report, we describe a possible drug interaction in a patient who had been using turmeric supplements and semaglutide injections and presented with elevated liver transaminases and bilirubin, with improvement upon cessation of the supplement.

Twee patiënten met acute toxische hepatitis na recente inname van thee

Two patients with toxic hepatitis after tea ingestion Drug-induced liver injury (DILI) is common and can manifest in various degrees: from asymptomatic increased transaminases to hepatocellular jaundice with an elevated total and direct bilirubin to acute liver failure. When accompanied by jaundice, there is a mortality rate of 10%. In acute liver failure, referral to a tertiary centre is necessary. This article emphasizes the consideration of herbal and dietary supplements (HDS). The use of HDS in Europe and the US is rising. Some studies state that 1 out of 3 to 1 out of 2 Americans take dietary supplements, which raises concerns about HDS-related toxic hepatitis. HDS involve any supplement that could cause liver damage, including herbs, vitamins, minerals, amino acids and proteins. The prevalence of hepatotoxicity is underestimated. DILI is a diagnosis of exclusion. Diseases that should be excluded, are viral hepatitis, non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), hereditary hemochromatosis, autoimmune hepatitis, Wilson’s disease and alpha-1 antitrypsin deficiency. If there is an increased total and direct bilirubin with or without cholestasis, bile duct stones and hepatobiliary malignancies should be excluded. A liver biopsy may be necessary if the diagnosis is unclear or when several diagnoses are plausible. Liver damage usually occurs within 1 to 6 months after starting the product and is usually reversible. It is important to bear in mind HDS when considering DILI as the incidence of HDS is clearly increasing.

Clinical characteristics and prognosis of non-APAP drug-induced acute liver failure: a large multicenter cohort study

BackgroundThere is growing recognition of natural history, complications, and outcomes of patients who develop non-acetaminophen (APAP) drug-induced acute liver failure (ALF). To clarify high-risk factors and develop a nomogram model to predict transplant-free survival (TFS) in patients with non-APAP drug-induced ALF.MethodsPatients with non-APAP drug-induced ALF from 5 participating centers were retrospectively analyzed. The primary endpoint was 21-day TFS. Total sample size was 482 patients.ResultsRegarding causative agents, the most common implicated drugs were herbal and dietary supplements (HDS) (57.0%). The hepatocellular type (R ≥ 5) was the main liver injury pattern (69.0%). International normalized ratio, hepatic encephalopathy grades, the use of vasopressor, N-acetylcysteine, or artificial liver support system were associated with TFS and incorporated to construct a nomogram model (drug-induced acute liver failure-5, DIALF-5). The AUROC of DIALF-5 for 7-day, 21-day, 60-day, and 90-day TFS in the internal cohort were 0.886, 0.915, 0.920, and 0.912, respectively. Moreover, the AUROC of DIALF-5 for 21-day TFS had the highest AUROC, which was significantly higher than 0.725 of MELD and 0.519 of KCC (p < 0.05), numerically higher than 0.905 of ALFSG-PI but without statistical difference (p > 0.05). These results were successfully validated in the external cohort (147 patients).ConclusionsBased on easily identifiable clinical data, the novel DIALF-5 model was developed to predict transplant-free survival in non-APAP drug-induced ALF, which was superior to KCC, MELD and had a similar prediction performance to ALFSG-PI but is more convenient, which can directly calculate TFS at multiple time points.

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, &quot;Liver injury attributed to HDS&quot;, 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

IntroductionThe 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. MethodsAn 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. ResultsOverall, 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. ConclusionHDS 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.

S3072 Liver Injury Caused by a Weight Loss Supplement Containing Green Tea Extract and Garcinia Cambogia

Introduction: Herbal-induced liver injury (HILI) is a growing topic worldwide, and herbal and dietary supplements (HDS) are the second leading class of compounds after antimicrobials causing liver injury in the United States. It is thought that many cases go unrecognized, as patients fail to mention their use of HDS. This is a case of mild liver injury in a young woman after taking a short course of a weight loss supplement containing a garcinia cambogia (GC) and green tea extract (GTE). Case Description/Methods: A 45-year-old female with a history of obesity presented to clinic with elevated liver enzymes identified on routine labs from two weeks prior. Medication reconciliation revealed that one month prior, she started a 15-day course of Revert 10.0 by Natureal for weight loss. She stopped taking the supplement on her own as she felt it was not helpful. Her only prescription medication was her oral contraceptive pill. She was born in the United States and denied any prior history of liver disease. She was asymptomatic with no nausea, abdominal pain, or jaundice. Her physical exam was unremarkable. Baseline laboratory values from six months prior showed AST 18 U/L (normal < 40), ALT 14 U/L (normal < 32), ALP 76 U/L (normal 39-117), TBili 0.4 mg/dL (normal < 1.2). Her liver tests after one week of using Revert 10.0 revealed elevations of AST to 49 and ALT to 83, with normal ALP 61, and TBili 0.2. LFTs after two weeks showed further rises in AST to 66, and ALT to 112, with normal ALP 66, and TBili 0.2. Her viral hepatitis panel was non-reactive. An abdominal ultrasound and CT scan of the abdomen/pelvis showed no abnormalities with normal echogenicity and liver morphology. Two weeks after withdrawing the supplement, her LFTs had returned to normal, AST 24, ALT 26, ALP 72, and TBili 0.2. (Figure) Discussion: This is the first report of liver injury from Revert 10.0. We encourage clinicians to consider HILI in patients with even mild laboratory abnormalities, and to conduct thorough history-taking. While GC and GTE are both known hepatotoxins, there are no cases reported of the two agents working in conjunction to cause HILI. Furthermore, the Roussel Uclaf Causality Assessment Method, the gold standard for HILI diagnosis does not consider the potential for synergy between multiple known hepatotoxic agents. Our case highlights that further research should explore how synergy of multiple supplements can affect presentation of HILI.Figure 1.: Liver Enzyme Trend Over Time

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.

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.

AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury.

AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury.

Herbal and Dietary Supplement Use among Adult Patients Undergoing Treatment at a Tertiary Hospital Cancer Center

AbstractThe use of herbal and dietary supplement in cancer patients has been increasing over the past years, while the risk of its adverse effects and undesirable reactions with conventional treatment has also been accumulating. Limited studies involving perception of herbal and dietary supplements (HDS) by cancer patients have been conducted in our setting. An initial survey was conducted among adult cancer patients undergoing treatment at the Zamboanga City Medical Center (ZCMC) Cancer Institute. HDS users were recruited for focus group discussion (FGD) via purposive sampling. A total of four groups were conducted. Clinical and demographic data were presented through descriptive statistics while data from the FGD were subjected to coding and thematic analysis. Among 22 respondents, more than half (65.4%) of the participants were noted to have used HDS and most (54.5%) were breast cancer patients with stage-II and -III disease. Treatment of cancer, coping with chemotherapy, and relief of symptoms were the major reasons for use. Majority (36.36%) were influenced by the media/internet and most (50%) did not disclose information to their physician. Eight respondents, whose income were below minimum wage, spent more than 25% of their income on HDS, with some having spent more than 50%. This may seriously limit funds and result in failure to adhere to treatment. Among cancer patients in ZCMC, HDS use is widely practiced and half of them do not disclose this information to their physicians. The expenditure on HDS consumes 25 to 50% of the population's meager monthly income. The secrecy surrounding its use and attendant cost may possibly limit adherence and adversely affect outcomes.

Setting up criteria for drug-induced autoimmune-like hepatitis through a systematic analysis of published reports.

Nitrofurantoin, minocycline, methyldopa and infliximab, have been found to induce autoimmune‐like hepatitis (DI‐AILH). Evidence for other drugs and herbal and dietary supplements (HDS) is unclear. The aims of the study were to establish criteria to define and review the published evidence of suspected DI‐AILH. Search was undertaken in Pubmed using search terms “drug‐induced liver injury,” “autoimmune hepatitis,” and “drug‐induced autoimmune hepatitis.” DI‐AILH was defined as (1) drug as a potential trigger of liver injury with autoimmune features and histological findings compatible with AIH; (2) no or incomplete recovery or worsening of liver tests after discontinuation of the drug; (3) corticosteroids requirement or spontaneous recovery; (4) follow‐up without immunosuppression (IS) and no relapse of AIH at least 6 months after discontinuation of IS; and (5) drugs potentially inducing AILH with a chronic course. Cases fulfilling the first four criteria were considered probable DI‐AILH with three possible DI‐AILH. A total of 186 case reports were identified for conventional drugs (n = 148; females 79%; latency 2.6 months) and HDS (n = 38; females 50%). The most commonly reported agents of DI‐AILH were interferons (n = 37), statins (n = 24), methylprednisolone (MPS) (n = 16), adalimumab (n = 10), imatinib (n = 8), and diclofenac (n = 7). Tinospora cordifolia and Khat were the only HDS with probable DI‐AILH cases. No relapses of AIH were observed when IS was stopped after interferons, imatinib, diclofenac, and methylprednisolone. Conclusion: Beyond well‐recognized nitrofurantoin, methyldopa, hydralazine, minocycline, and infliximab as causes of DI‐AILH, interferons, imatinib, adalimumab, and MPS were the best‐documented agents leading to probable DI‐AILH. Khat and Tinospora cordifolia were the only HDS found to be able to induce DI‐AILH. Long‐term immunosuppression appears to be rarely required in patients with DI‐AILH due to these drugs.

Trends in Herbal and Dietary Supplement Use Among U. S. Adults with Chronic Liver Disease

Herbal and dietary supplements (HDS) are used by over 50% of Americans, but commonly their use is not reported to healthcare providers. The aim of this study is to determine the prevalence of HDS use among patients with Chronic Liver Disease (CLD), with a focus on those using supplements known to cause hepatotoxicity. We accessed 61,951 individuals polled in the NHANES database between 2001-2011, which represented a population size of 1,763,482,931. 573 respondents reported a history of CLD (population size of 19,998,331.655). Of those 573 respondents, 41 respondents (population size 1,399,884) endorsed using HDS that are associated with causing hepatotoxicity, which are listed under the NIH complied master list. Our study demonstrates the need for better counseling of patients on the potential risks of these readily available products.

Liver Transplantation for Acute Liver Injury in Asians Is More Likely Due to Herbal and Dietary Supplements.

Drug-induced liver injury (DILI) due to medications and herbal and dietary supplements (HDSs) is a major cause of acute liver injury leading to liver transplantation (LT). This study used United Network for Organ Sharing LT data to analyze severe HDS-induced acute liver injury in the United States. By convention, patients with acute DILI are listed as "Acute Hepatic Necrosis" (AHN) under the subheading "AHN: Drug Other Specify." All patients waitlisted from 1994 to 2020 were divided into 3 subgroups: "HDS DILI," "Non-HDS DILI," and "AHN: unknown drug." Analyses were performed to identify epidemiologic differences between patients with HDS DILI and non-HDS DILI. A subanalysis was performed for transplanted patients, including longitudinal changes. Of 1875 patients waitlisted for LT, 736 (39.2%) underwent LT. The proportion of Asian patients in the HDS DILI group was significantly higher compared with that in the non-HDS DILI group (17.4% versus 3.8%; P<0.001). Excluding acetaminophen cases, the proportion of Black patients in the HDS DILI versus non-HDS group was significantly lower (8.7% versus 25.3%; P<0.001). Waitlisted patients with HDS DILI were significantly older (median age, 38 years for HDS DILI versus 31 years for non-HDS DILI; P=0.03). Lastly, the number of patients requiring LT due to HDS DILI increased significantly over time with more than 70% of cases occurring in the last 10years (2010-2020) compared with the prior 15years (1994-2009; Ptrend =0.001). Ethnicity may help in identifying the cause of severe acute DILI, a growing problem as more patients experiment with HDS.

Garcinia cambogia, Either Alone or in Combination With Green Tea, Causes Moderate to Severe Liver Injury

Garcinia cambogia, either alone or with green tea, is commonly promoted for weight loss. Sporadic cases of liver failure from G cambogia have been reported, but its role in liver injury is controversial.Among 1418 patients enrolled in the Drug-Induced Liver Injury Network (DILIN) from 2004 to 2018, we identified 22 cases (adjudicated with high confidence) of liver injury from G cambogia either alone (n = 5) or in combination with green tea (n = 16) or Ashwagandha (n = 1). Control groups consisted of 57 patients with liver injury from herbal and dietary supplements (HDS) containing green tea without G cambogia and 103 patients from other HDS.Patients who took G cambogia were between 17 and 54 years, with liver injury arising 13-223 days (median = 51) after the start. One patient died, one required liver transplantation, and 91% were hospitalized. The liver injury was hepatocellular with jaundice. Although the peak values of aminotransferases were significantly higher (2001 ± 1386 U/L) in G cambogia group (P < .018), the median time for improvement in total bilirubin was significantly lower compared with the control groups (10 vs 17 and 13 days; P = .03). The presence of HLA-B∗35:01 allele was significantly higher in the G cambogia containing HDS (55%) compared with patients because of other HDS (19%) (P = .002) and those with acute liver injury from conventional drugs (12%) (P = 2.55 × 10-6).The liver injury caused by G cambogia and green tea is clinically indistinguishable. The possible association with HLA-B∗35:01 allele suggests an immune-mediated mechanism of injury.gov number: NCT00345930.

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

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. 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). 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). 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.

Drug-induced liver failure secondary to Psoralea corylifolia: a case report and literature review

Background: We present a case of a 56-year-old male presenting with acute liver failure requiring transplantation after intake of Psoralea corylifolia for five weeks. Acute liver injury secondary to herbal and dietary supplements (HDS) should be suspected in patients presenting with acute liver failure. Awareness of HDS’s associated risk is important in the setting of their increasing use, with at least 23% of adults in the United States reporting using alternative therapies. One such implicated remedy is the plant Psoralea corylifolia, used in Ayurvedic medicine as an alternative treatment for conditions including psoriasis and vitiligo. Aims and methods: A literature review using Ovid-Medline was undertaken to identify similar cases. Other potential causes were excluded clinically, radiologically and serologically to establish causality. Sections of the recipient liver were formalin-fixed and paraffin-embedded for staining with haematoxylin and eosin and other routine special stains. Results and conclusions: Sections of the liver showed extensive necrosis varying from submassive to massive. No other cause for the liver injury was identified on clinical correlation. Thus histological findings were compatible with a clinical history of drug induced liver injury. This report highlights a case of Psoralea corylifolia-induced acute liver failure requiring transplantation, compared to seven other cases in the literature, with one reported subsequent death. The popularity of Psoralea corylifolia as an Ayurvedic remedy highlights the clinical significance of its potential hepatotoxicity. A clinician should have a high index of suspicion for HDS use with patients presenting with acute liver failure.

Evaluation of drug-induced liver injury as etiology for acute liver failure in Brazil

Introduction and objectivesLittle is known about the etiology of acute liver failure (ALF) in Latin America. The objective of this paper is to investigate the main etiologies of ALF in Brazil, including Drug Induced Liver Injury (DILI) using stringent causality criteria. Patients or material and methodsAll the cases of individuals who underwent liver transplantation (LT) in 12 centers in Brazil for ALF were reviewed. When DILI was stated as the cause of ALF, causality criteria were applied on site by the main investigator in order to rule out other etiologies. Results325 individuals had ALF mainly for unknown reasons (34%), DILI (27%) and AIH (18%). Reassessment of the 89 cases of DILI, using stringent causality criteria, revealed that in only 42 subjects could DILI be confirmed as the cause of ALF. Acetaminophen (APAP) toxicity (n = 3) or DILI due to herbal and dietary supplements (HDS) (n = 2) were not commonly observed. ConclusionsUndetermined etiology and DILI are the main causes of ALF in Brazil. However, APAP toxicity and DILI due to HDS are mostly uncommon.