{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:14:51Z","timestamp":1787026491818,"version":"build-2736575974"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Gastroenterol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Complementary and alternative medicine (CAM)-related hepatotoxicity is a growing global concern. We utilized multi-modal analysis to characterize CAM product safety and identify predictors of severe liver injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study analyzed 386 CAM products from 91 consecutive patients (mean 4.2 products\/patient) presenting with CAM-related adverse events at a tertiary center in South India (2021\u20132023). Product-level analyses characterize the CAM supply chain while patient-level analyses inform clinical outcome associations. Investigations included ingredient documentation, heavy metal quantification, and GC-MS compound profiling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The mean patient age was 48.2 years (75.8% male). ACLF occurred in 39.6% of all patients (36\/91) and 41.9% of those with hepatic adverse events (36\/86), with associated mortality of 38.9% (14\/36) compared to 10.9% (6\/55) in non-ACLF presentations (OR 5.20, P = 0.004). Heavy metals exceeded WHO limits in many products: mercury (34%), cadmium (25%), arsenic (21%), and lead (14%). Cadmium exposure exceeding WHO limits showed a strong association with ACLF (75.9% vs 22.6%, P&amp;lt;0.001, FDR q&amp;lt;0.001). The association with mortality did not reach statistical significance after correction for multiple comparisons (34.5% vs 16.1%, uncorrected P = 0.061, FDR q=0.24). Undeclared pharmaceutical adulteration (at least one adulterant found in 27.7% of products; exposure to at least one adulterated product in 46.2% of patients) and animal-derived content (31.3%) were prevalent. Notably, unlabeled product consumption significantly predicted mortality (P = 0.025).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CAM-associated liver injury frequently manifests as ACLF with high mortality, driven by pervasive heavy metal contamination and adulteration. Unlabeled product exposure is a strong mortality predictor, highlighting the urgent need for mandatory product surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgstr.2026.1784785","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:37:02Z","timestamp":1773207422000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Analysis of 386 alternative medicinal products implicated in liver injury reveal clinically relevant associations with potentially hepatotoxic botanicals, pharmaceutical adulteration, heavy metal contamination, and undisclosed animal content"],"prefix":"10.3389","volume":"5","author":[{"given":"Cyriac Abby","family":"Philips","sequence":"first","affiliation":[{"name":"Department of Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]},{"name":"Clinical Research Division, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]},{"name":"Division of Complementary and Alternative Medicine and The Liver, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharun Tom","family":"Oommen","sequence":"additional","affiliation":[{"name":"Department of Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]},{"name":"Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif Hussain","family":"Theruvath","sequence":"additional","affiliation":[{"name":"Clinical Research Division, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]},{"name":"Division of Complementary and Alternative Medicine and The Liver, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryalakshmi","family":"Sreemohan","sequence":"additional","affiliation":[{"name":"Clinical Research Division, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]},{"name":"Division of Complementary and Alternative Medicine and The Liver, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambily","family":"Baby","sequence":"additional","affiliation":[{"name":"Clinical Research Division, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]},{"name":"Division of Complementary and Alternative Medicine and The Liver, The Liver Institute, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwan","family":"Ahamed","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajit","family":"Tharakan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Augustine","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Advanced GI Endoscopy, Center of Excellence in Gastrointestinal Sciences, Rajagiri Hospital","place":["Aluva, Kerala, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2425822","DOI":"10.1001\/jamanetworkopen.2024.25822","article-title":"Estimated exposure to 6 potentially hepatotoxic botanicals in US adults","volume":"7","author":"Likhitsup","year":"2024","journal-title":"JAMA Netw Open"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2025.11.004","article-title":"The DILI-Inpt prognostic score to Identify hospitalized Idiosyncratic DILI patients at risk for Adverse outcomes","author":"Likhitsup","year":"2025","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e70327","DOI":"10.1111\/liv.70327","article-title":"DILI is an important cause of hepatocellular and mixed liver injury-a nationwide prospective study on elevated liver enzymes","volume":"45","author":"Sigurdarson","year":"2025","journal-title":"Liver Int"},{"key":"B4","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.cgh.2024.06.030","article-title":"Drug-induced liver injury in Latin America: 10-year experience of the Latin American DILI (LATINDILI) network","volume":"23","author":"Bessone","year":"2025","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-021-10144-3","article-title":"Drug-induced liver injury: Asia Pacific Association of Study of Liver consensus guidelines","volume":"15","author":"Devarbhavi","year":"2021","journal-title":"Hepatol Int"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000000201","article-title":"Drug-induced acute-on-chronic liver failure in asian patients","volume":"114","author":"Devarbhavi","year":"2019","journal-title":"Am J Gastroenterol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2020.08.008","article-title":"Outcomes and predictors of mortality in patients with drug-induced liver injury at a tertiary hospital in South India: A Single-Centre Experience","volume":"11","author":"Sunil Kumar","year":"2021","journal-title":"J Clin Exp Hepatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e0270","DOI":"10.1097\/HC9.0000000000000270","article-title":"Ashwagandha-induced liver injury-A case series from India and literature review","volume":"7","author":"Philips","year":"2023","journal-title":"Hepatol Commun"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e0064","DOI":"10.1097\/HC9.0000000000000064","article-title":"A series of homeopathic remedies-related severe drug-induced liver injury from South India","volume":"7","author":"Theruvath","year":"2023","journal-title":"Hepatol Commun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2021.06.021","article-title":"Herbal immune booster-induced liver injury in the COVID-19 pandemic - a case series","volume":"11","author":"Nagral","year":"2021","journal-title":"J Clin Exp Hepatol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1355","article-title":"A single-center experience on outcomes of complementary and alternative medicine use among patients with cirrhosis","volume":"3","author":"Philips","year":"2019","journal-title":"Hepatol Commun"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastrohep.2025.502520","article-title":"Unveiling the hidden risk: Herbal and dietary supplement consumption in liver disease patients","volume":"48","author":"Canga","year":"2025","journal-title":"Gastroenterol Hepatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/srep17475","article-title":"toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM)","volume":"5","author":"Coghlan","year":"2015","journal-title":"Sci Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s00228-012-1353-z","article-title":"Contamination and adulteration of herbal medicinal products (HMPs): an overview of systematic reviews","volume":"69","author":"Posadzki","year":"2013","journal-title":"Eur J Clin Pharmacol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-024-01484-8","article-title":"Investigation of the role of chemical analysis in causality assessment of herbal and dietary supplement-induced liver injury","volume":"48","author":"Halegoua-DeMarzio","year":"2025","journal-title":"Drug Saf"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001259","article-title":"ACG clinical guideline: diagnosis and management of idiosyncratic drug-induced liver injury","volume":"116","author":"Chalasani","year":"2021","journal-title":"Am J Gastroenterol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1001\/jama.300.8.915","article-title":"Lead, mercury, and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the Internet","volume":"300","author":"Saper","year":"2008","journal-title":"JAMA"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/toxics12060388","article-title":"Cadmium exposure: mechanisms and pathways of toxicity and implications for human health","volume":"12","author":"Qu","year":"2024","journal-title":"Toxics"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2025.105942","article-title":"The association between cadmium exposure and the risk of early liver disease: A systematic review and meta-analysis","volume":"163","author":"Zhang","year":"2025","journal-title":"Regul Toxicol Pharmacol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32689","article-title":"AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury","volume":"77","author":"Fontana","year":"2023","journal-title":"Hepatology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(00)01972-6","article-title":"Toxic heavy metals and undeclared drugs in Asian herbal medicines","volume":"23","author":"Ernst","year":"2002","journal-title":"Trends Pharmacol Sci"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.595335","article-title":"Heavy metal contaminations in herbal medicines: determination, comprehensive risk assessments, and solutions","volume":"11","author":"Luo","year":"2021","journal-title":"Front Pharmacol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.2147\/DHPS.S305953","article-title":"Adulterated traditional-herbal medicinal products and its safety signals in Malaysia","volume":"13","author":"Ariffin","year":"2021","journal-title":"Drug Healthc Patient Saf"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v13.i9.1019","article-title":"Herbal and dietary supplement induced liver injury: Highlights from the recent literature","volume":"13","author":"Woo","year":"2021","journal-title":"World J Hepatol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"39S","DOI":"10.1177\/0148607115595978","article-title":"Phytosterols, lipid administration, and liver disease during parenteral nutrition","volume":"39","author":"Zaloga","year":"2015","journal-title":"JPEN J Parenter Enteral Nutr"},{"key":"B26","doi-asserted-by":"publisher","first-page":"206ra137","DOI":"10.1126\/scitranslmed.3006898","article-title":"Phytosterols promote liver injury and Kupffer cell activation in parenteral nutrition-associated liver disease","volume":"5","author":"El Kasmi","year":"2013","journal-title":"Sci Transl Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/807354","article-title":"Linoleic acid induced acute hepatitis: A case report and review of the literature","volume":"2015","author":"Bilal","year":"2015","journal-title":"Case Rep Hepatol"}],"container-title":["Frontiers in Gastroenterology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgstr.2026.1784785\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:37:03Z","timestamp":1773207423000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgstr.2026.1784785\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":27,"alternative-id":["10.3389\/fgstr.2026.1784785"],"URL":"https:\/\/doi.org\/10.3389\/fgstr.2026.1784785","relation":{},"ISSN":["2813-1169"],"issn-type":[{"value":"2813-1169","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"article-number":"1784785"}}