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

Published:January 09, 2021DOI:


      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.


      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.


      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%).


      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.

      Graphical abstract


      Abbreviations used in this paper:

      AAS (anabolic androgenic steroids), ALF (acute liver failure), ALP (alkaline phosphatase), ALT (alanine transaminase), DILI (drug-induced liver injury), DILIN (Drug-Induced Liver Injury Network), HDS (herbal and dietary supplements), HILI (herbal-induced liver injury), LATINDILIN (Latin America DILI Network), RUCAM (Roussel Uclaf Causality Assessment Method)
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        • Calitz C.
        • Du Plessis L.
        • Gouws C.
        • et al.
        Herbal hepatotoxicity: current status, examples, and challenges.
        Expert Opin Drug Metab Toxicol. 2015; 11: 1551-1565
        • Navarro V.J.
        • Khan I.
        • Björnsson E.
        • et al.
        Liver injury from herbal and dietary supplements.
        Hepatology. 2017; 65: 363-373
        • Matthews H.B.
        • Lucier G.W.
        • Fisher K.D.
        Medicinal herbs in the United States: research needs.
        Environ Health Perspect. 1999; 107: 773-778
        • Navarro V.J.
        • Barnhart H.
        • Bonkovsky H.L.
        • et al.
        Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network.
        Hepatology. 2014; 60: 1399-1408
        • Björnsson E.S.
        • Bergmann O.M.
        • Björnsson H.K.
        • et al.
        Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of iceland.
        Gastroenterology. 2013; 144: 1419-1425.e3
        • Vega M.
        • Verma M.
        • Beswick D.
        • et al.
        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.
        Drug Saf. 2017; 40: 783-787
        • Medina-Caliz I.
        • Garcia-Cortes M.
        • Gonzalez-Jimenez A.
        • et al.
        Herbal and dietary supplement-induced liver injuries in the Spanish DILI registry.
        Clin Gastroenterol Hepatol. 2018; 16: 1495-1502
        • Douros A.
        • Bronder E.
        • Andersohn F.
        • et al.
        Herb-induced liver injury in the berlin case-control surveillance study.
        Int J Mol Sci. 2016; 17: 1-11
        • Andrade R.J.
        • Medina-Caliz I.
        • Gonzalez-Jimenez A.
        • et al.
        Hepatic damage by natural remedies.
        Semin Liver Dis. 2018; 38: 21-40
        • Devarbhavi H.
        • Dierkhising R.
        • Kremers W.K.
        • et al.
        Single-center experience with drug-induced liver injury from India: causes, outcome, prognosis, and predictors of mortality.
        Am J Gastroenterol. 2010; 105: 2396-2404
        • Daǧ M.S.
        • Aydinli M.
        • Öztürk Z.A.
        • et al.
        Drug- and herb-induced liver injury: a case series from a single center.
        Turkish J Gastroenterol. 2014; 25: 41-45
        • Zhu Y.
        • Niu M.
        • Chen J.
        • et al.
        Hepatobiliary and pancreatic: comparison between Chinese herbal medicine and Western medicine-induced liver injury of 1985 patients.
        J Gastroenterol Hepatol. 2016; 31: 1476-1482
        • Wai C.T.
        • Tan B.H.
        • Chan C.L.
        • et al.
        Drug-induced liver injury at an Asian center: a prospective study.
        Liver Int. 2007; 27: 465-474
        • Suk K.T.
        • Kim D.J.
        • Kim C.H.
        • et al.
        A prospective nationwide study of drug-induced liver injury in Korea.
        Am J Gastroenterol. 2012; 107: 1380-1387
        • WHO
        WHO traditional medicine strategy: 2014-2023.
        (Available at:)
        • Bessone F.
        • Hernandez N.
        • Lucena M.I.
        • et al.
        The Latin American DILI Registry experience: a successful ongoing collaborative strategic initiative.
        Int J Mol Sci. 2016; 17: 313
        • Bessone F.
        • Hernandez N.
        • Mendizabal M.
        • et al.
        When the creation of a consortium provides useful answers: experience of the Latin American DILI Network (LATINDILIN).
        Clin Liver Dis. 2019; 13: 51-57
        • Santos G.
        • Gasca J.
        • Parana R.
        • et al.
        Profile of herbal and dietary supplements induced liver injury in Latin America: a systematic review of published reports.
        Phyther Res. 2020;
        • Aithal G.P.
        • Watkins P.B.
        • Andrade R.J.
        • et al.
        Case definition and phenotype standardization in drug-induced liver injury.
        Clin Pharmacol Ther. 2011; 89: 806-815
        • Robles-Diaz M.
        • Lucena M.I.
        • Kaplowitz N.
        • et al.
        Use of hy’s law and a new composite algorithm to predict acute liver failure in patients with drug-induced liver injury.
        Gastroenterology. 2014; 147: 109-118.e5
        • Navarro V.J.
        • Lucena M.I.
        Hepatotoxicity induced by herbal and dietary supplements.
        Semin Liver Dis. 2014; 34: 172-193
        • Teschke R.
        • Eickhoff A.
        Herbal hepatotoxicity in traditional and modern medicine: actual key issues and new encouraging steps.
        Front Pharmacol. 2015; 6: 72
        • Larrey D.
        • Faure S.
        Herbal medicine hepatotoxicity: a new step with development of specific biomarkers.
        J Hepatol. 2011; 54: 599-601
        • Navarro V.
        • Avula B.
        • Khan I.
        • et al.
        The contents of herbal and dietary supplements implicated in liver injury in the United States are frequently mislabeled.
        Hepatol Commun. 2019; 3: 792-794
        • Björnsson E.
        • Talwalkar J.
        • Treeprasertsuk S.
        • et al.
        Drug-induced autoimmune hepatitis: clinical characteristics and prognosis.
        Hepatology. 2010; 51: 2040-2048
        • Lucena M.I.
        • Kaplowitz N.
        • Hallal H.
        • et al.
        Recurrent drug-induced liver injury (DILI) with different drugs in the Spanish Registry: the dilemma of the relationship to autoimmune hepatitis.
        J Hepatol. 2011; 55: 820-827
        • Suzuki A.
        • Brunt E.M.
        • Kleiner D.E.
        • et al.
        The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury.
        Hepatology. 2011; 54: 931-939
        • Wang Y.
        • Wang L.
        • Saxena R.
        • et al.
        Clinicopathological features of He Shou Wu-induced liver injury: this ancient anti-aging therapy is not liver-friendly.
        Liver Int. 2019; 39: 389-400
        • Manso G.
        • López-Rivas L.
        • Salgueiro M.E.
        • et al.
        Continuous reporting of new cases in Spain supports the relationship between Herbalife products and liver injury.
        Pharmacoepidemiol Drug Saf. 2011; 20: 1080-1087
        • Li C.
        • Rao T.
        • Chen X.
        • et al.
        HLA-B∗35:01 allele is a potential biomarker for predicting Polygonum multiflorum–induced liver injury in humans.
        Hepatology. 2019; 70: 346-357
        • Hillman L.
        • Gottfried M.
        • Whitsett M.
        • et al.
        Clinical features and outcomes of complementary and alternative medicine induced acute liver failure and injury.
        Am J Gastroenterol. 2016; 111: 958-965
        • Hayashi P.H.
        • Rockey D.C.
        • Fontana R.J.
        • et al.
        Death and liver transplantation within 2 years of onset of drug-induced liver injury.
        Hepatology. 2017; 66: 1275-1285
        • Aiso M.
        • Takikawa H.
        • Tsuji K.
        • et al.
        Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan.
        Hepatol Res. 2019; 49: 105-110
        • Lee B.M.
        • Lee W.C.
        • Jang J.Y.
        • et al.
        Clinical features of drug-induced liver injury according to etiology.
        J Korean Med Sci. 2015; 30: 1815-1820
        • Zhu Y.
        • Niu M.
        • Wang J.B.
        • et al.
        Predictors of poor outcomes in 488 patients with herb induced liver injury.
        Turkish J Gastroenterol. 2019; 30: 47-58
        • Chen S.S.
        • Yu K.K.
        • Huang C.
        • et al.
        The characteristics and clinical outcome of drug-induced liver injury in a Chinese hospital: a retrospective cohort study.
        Med (United States). 2016; 95e4683
        • Abid A.
        • Subhani F.
        • Kayani F.
        • et al.
        Drug induced liver injury is associated with high mortality: a study from a tertiary care hospital in Pakistan.
        PLoS One. 2020; 15e0231398