AACT Herbal Dietary Supplements SIG Abstracts July 2017 1. A nationwide study of the incidence rate of herb-induced liver injury in Korea. Cho JH, Oh DS, Hong SH, Ko H, Lee NH, Park SE, Han CW, Kim SM, Kim YC, Kim KS, Choi CW, Shin SM, Kim KT, Choi HS, Lee JH, Kim JY, Kang JY, Lee DS, Ahn YC, Son CG. Arch Toxicol. 2017 Jun 20. doi: 10.1007/s00204-017-2007-9. [Epub ahead of print] Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy's law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12-1.08; women: 0.95%, 95% CI 0.19-1.68] and described its features in hospitalized participants. DOI: 10.1007/s00204-017-2007-9 PMID: 28634823 2. Hepatotoxicity associated with weight loss or sports dietary supplements, including OxyELITE Pro™ - United States, 2013. Chatham-Stephens K, Taylor E, Chang A, Peterson A, Daniel J, Martin C, Deuster P, Noe R, Kieszak S, Schier J, Klontz K, Lewis L. Drug Test Anal. 2017 Jan;9(1):68-74. doi: 10.1002/dta.2036. Epub 2016 Aug 4. In September 2013, the Hawaii Department of Health (HDOH) was notified of seven adults who developed acute hepatitis after taking OxyELITE Pro™, a weight loss and sports dietary supplement. CDC assisted HDOH with their investigation, then conducted case-finding outside of Hawaii with FDA and the Department of Defense (DoD). We defined cases as acute hepatitis of unknown etiology that occurred from April 1, 2013, through December 5, 2013, following exposure to a weight loss or muscle-building dietary supplement, such as OxyELITE Pro™. We conducted case-finding through multiple sources, including data from poison centers (National Poison Data System [NPDS]) and FDA MedWatch. We identified 40 case-patients in 23 states and two military bases with acute hepatitis of unknown etiology and exposure to a weight loss or muscle building dietary supplement. Of 35 case-patients who reported their race, 15 (42.9%) reported white and 9 (25.7%) reported Asian. Commonly reported symptoms included jaundice, fatigue, and dark urine. Twenty-five (62.5%) case-patients reported taking OxyELITE Pro™. Of these 25 patients, 17 of 22 (77.3%) with available data were hospitalized and 1 received a liver transplant. NPDS and FDA MedWatch each captured seven (17.5%) case-patients. Improving the ability to search surveillance systems like NPDS and FDA MedWatch for individual and grouped dietary supplements, as well as coordinating case-finding with DoD, may benefit ongoing surveillance efforts and future outbreak responses involving adverse health effects from dietary supplements. This investigation highlights opportunities and challenges in using multiple sources to identify cases of suspected supplement associated adverse events. DOI: 10.1002/dta.2036 PMID: 27367536 [Indexed for MEDLINE] 3. Urgent Liver Transplantation for Dietary Supplements: An Under-Recognized Problem. Wong LL, Lacar L, Roytman M, Orloff SL. Transplant Proc. 2017 Mar;49(2):322-325. doi: 10.1016/j.transproceed.2016.11.041. BACKGROUND: The recent outbreak of acute liver failure caused by herbal/dietary supplements (HDS) in Hawaii prompted evaluation of those patients who underwent emergency liver transplantation (LT) for HDS in the United States. METHODS: We queried the Scientific Registry of Transplant Recipients (2003-2015) to identify patients who underwent urgent LT for acute hepatic necrosis (AHN) and identified those with HDS use. This group of patients was then characterized. RESULTS: Of 2408 adult cases, 625 were characterized as a drug-induced liver injury. The majority of cases (n = 300) were due to acetaminophen toxicity, but the fourth highest category was due to HDS (n = 21). Of these 21 cases caused by HDS, 13 did not list the specific agent responsible, mean age was 36 years, and all cases occurred after 2007. There probably are more cases because 25% of all LT cases in the study did not list a specific reason for liver failure and 20% of all drug-induced liver failure did not list a specific drug. CONCLUSIONS: Herbal/ supplement use is the fourth most common cause of drug-induced AHN requiring LT, albeit an underestimation of the problem. Detailed questioning of patients and their support systems regarding herbal/supplement use and better reporting are imperative to further define this problem and identify products that have the potential to lead to liver failure. DOI: 10.1016/j.transproceed.2016.11.041 PMID: 28219592 [Indexed for MEDLINE] 4. Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation. Lunsford KE, Bodzin AS, Reino DC, Wang HL, Busuttil RW. World J Gastroenterol. 2016 Dec 7;22(45):10071-10076. doi: 10.3748/wjg.v22.i45.10071. Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients. DOI: 10.3748/wjg.v22.i45.10071 PMCID: PMC5143754 PMID: 28018115 [Indexed for MEDLINE] 5. Hepatotoxicity by herbs: a practical review of a neglected disease. Donet JA, Sornmayura K, Gulau M, Schiff E. Rev Gastroenterol Peru. 2016 Oct-Dec;36(4):350-353. Herbs are commonly used worldwide for the treatment of various diseases, constituting a multi-billion dollar market. Unfortunately, hepatotoxicity induced by herbs is also common. The true incidence and prevalence are not known. There is need for more strict regulations andexperimental and pre-clinical studies regarding its efficacy and safety. There is no gold standard for the diagnosis of herbs-induced liver injury (HILI) and it constitutes a diagnostic challenge for the clinician, where establishing causality could be cumbersome. Clinical presentation varies from asymptomatic cases with mildly abnormal liver tests to fulminant liver failure requiring liver transplantation. In this review, we will discuss the epidemiology, clinical manifestations, challenges and diagnostic approach of HILI and will also present some exemplary cases from the University of Miami, Division of Hepatology. PMID: 28062872 [Indexed for MEDLINE] 6. Hepatotoxicity evaluation of traditional Chinese medicines using a computational molecular model. Zhao P, Liu B, Wang C; Acute Liver Failure Study Team (ALFST). Clin Toxicol (Phila). 2017 Jun 8:1. doi: 10.1080/15563650.2017.1333123. [Epub ahead of print] BACKGROUND: Liver injury caused by traditional Chinese medicines (TCMs) is reported from many countries around the world. TCM hepatotoxicity has attracted worldwide concerns. OBJECTIVE: This study aims to develop a more applicable and optimal tool to evaluate TCM hepatotoxicity. METHODS: A quantitative structure-activity relationship (QSAR) analysis was performed based on published data and U.S. Food and Drug Administration's Liver Toxicity Knowledge Base (LTKB). RESULTS: Eleven herbal ingredients with proven liver toxicity in the literature were added into the dataset besides chemicals from LTKB. The finally generated QSAR model yielded a sensitivity of 83.8%, a specificity of 70.1%, and an accuracy of 80.2%. Among the externally tested 20 ingredients from TCMs, 14 hepatotoxic ingredients were all accurately identified by the QSAR model derived from the dataset containing natural hepatotoxins. CONCLUSIONS: Adding natural hepatotoxins into the dataset makes the QSAR model more applicable for TCM hepatotoxicity assessment, which provides a right direction in the methodology study for TCM safety evaluation. The generated QSAR model has the practical value to prioritize the hepatotoxicity risk of TCM compounds. Furthermore, an open-access international specialized database on TCM hepatotoxicity should be quickly established. DOI: 10.1080/15563650.2017.1333123 PMID: 28594241 7. The Incidence of Drug- and Herbal and Dietary Supplement-Induced Liver Injury: Preliminary Findings from Gastroenterologist-Based Surveillance in the Population of the State of Delaware. Vega M, Verma M, Beswick D, Bey S, Hossack J, Merriman N, Shah A, Navarro V; Drug Induced Liver Injury Network (DILIN). Drug Saf. 2017 May 29. doi: 10.1007/s40264-017-0547-9. [Epub ahead of print] BACKGROUND AND AIM: The population-based incidence rate of drug-induced liver injury (DILI) in the USA is not known. The Drug-Induced Liver Injury Network (DILIN) accrues cases of hepatotoxicity due to medications and herbal and dietary supplements (HDS) from limited geographical areas. The current analysis was an ancillary study of DILIN aimed at determining the annual incidence of DILI in the USA on a population basis, through surveillance in the state of Delaware. METHODS: At the outset of the study, there were 41 gastroenterologists in the state of Delaware and all agreed to participate in surveillance for DILI, which comprised active reporting of suspected cases to the DILIN.