A series of homeopathic remedies-related severe drug-induced liver injury from South India

Abstract

Introduction: Homeopathic remedies are highly diluted formulations without proven clinical benefits, traditionally believed not to cause adverse events. Nonetheless, published literature reveals severe local and non–liver-related systemic side effects. We present the first series on homeopathy-related severe drug-induced liver injury (DILI) from a single center. Methods: A retrospective review of records from January 2019 to February 2022 identified 9 patients with liver injury attributed to homeopathic formulations. Competing causes were comprehensively excluded. Chemical analysis was performed on retrieved formulations using triple quadrupole gas chromatography-mass spectrometry and inductively coupled plasma atomic emission spectroscopy. Results: Males predominated with a median age of 54 years. The most typical clinical presentation was acute hepatitis, followed by acute on chronic liver failure. All patients developed jaundice, and ascites were notable in one-third of the patients. Five patients had underlying chronic liver disease. COVID-19 prevention was the most common indication for homeopathic use. Probable DILI was seen in 77.8%, and hepatocellular injury predominated (66.7%). Four (44.4%) patients died (3 with chronic liver disease) at a median follow-up of 194 days. Liver histopathology showed necrosis, portal and lobular neutrophilic inflammation, and eosinophilic infiltration with cholestasis. A total of 29 remedies were consumed between 9 patients, and 15 formulations were analyzed. Toxicology revealed industrial solvents, corticosteroids, antibiotics, sedatives, synthetic opioids, heavy metals, and toxic phyto-compounds, even in ‘supposed’ ultra-dilute formulations. Conclusion: Homeopathic remedies potentially result in severe liver injury, leading to death in those with underlying liver disease. The use of mother tinctures, insufficient dilution, poor manufacturing practices, adulteration and contamination, and the presence of direct hepatotoxic herbals were the reasons for toxicity. Physicians, the public, and patients must realize that Homeopathic drugs are not ‘gentle placebos.’

Letter to the Editor: Homeopathic drug-induced liver injury—an example of biases pertaining to Roussel Uclaf causality assessment method

“… If any patients receive any comedication or dietary supplements, individual RUCAM assessment needs to be done for those comedications, which was not done in 4 patients. It should also be noted that the Methods section 1 has explained that those patients taking comedications were excluded. Still, the analysis includes them (Supplemental Table S3, http://links.lww.com/HC9/A317 ).…”

“… The histopathology data are irrelevant for diagnosing DILI as per the updated RUCAM, 2 as it has many similar features of primary hepatic or biliary diseases. 3 However, in the discussion part, 1 authors are trying to substantiate that the liver histopathologies identified are supposed to be due to homeopathic drugs. …”

“…Altogether the article has shown enough examples of selection and information biases with a weak causality link between homeopathic remedies and DILIs. From the overall review, it is understood that the conclusions derived from the given article 1 are irrelevant.…”

“…The study published by Theruvath et al 1 showed some serious flaws in data capturing and depiction. The authors should have depicted the data appropriately, especially concerning the Roussel Uclaf Causality Assessment Method (RUCAM) and observations related to gas chromatography-mass spectroscopy analysis (GC/MS).…”

A comprehensive review on the hepatotoxicity of herbs used in the Indian (Ayush) systems of alternative medicine

“…[7][8][9] Furthermore, a large series of patients with "Ayush-immune boosting" and homeopathic remediesrelated liver injury were recently published from the Indian subcontinent. [10,11] The Asia-Pacific Association for Study of Liver (APASL) drug-induced liver injury (DILI) guidelines faculty coined the term "Ayush-liver injury" for liver injury originating specifically from Indian CAM. [12] A multicentre study from the APASL demonstrated that ACLF in Asia-Pacific countries was predominantly due to CAM (inclusive of Ayurvedic herbs and herbal and dietary supplements) in approximately 72% of patients.…”