Tinospora cordifolia (Giloy) is an herbal supplement commonly used in the Indian alternative medicine system Ayurveda. This herb has been promoted to the public in India as an immune booster to prevent novel coronavirus disease 2019. However, small reports have recently shown an association between Giloy use and the development of herb‐induced liver injury (HILI) with autoimmune features in some patients. This large retrospective Indian multicenter study spanning 13 centers at nine locations was designed to identify features and outcomes of HILI temporally associated with Giloy use. Chemical and toxicological analyses of retrieved Giloy samples using state‐of‐the‐art methods were also performed. We report 43 patients, of whom more than half were female, with a median time from initial Giloy consumption to symptom onset of 46 days. Patients presented with acute hepatitis, acute worsening of chronic liver disease (CLD, the most common clinical presentation), or acute liver failure. Causality assessment revealed probable liver injury in 67.4%. The most common autoantibody detected was anti‐nuclear antibody. Liver biopsy in a subset revealed HILI associated with autoimmune features and hepatocyte and canalicular cholestasis and neutrophilic and eosinophilic infiltration. Conclusion: Giloy is associated with acute hepatitis with autoimmune features and can unmask autoimmune hepatitis (AIH) in people with silent AIH‐related CLD. Further studies on the safety (and efficacy) of untested but heavily promoted herbals in alternative systems of medicine are an unmet need in the interests of public health and are especially important during this global health emergency.

Some people create their own storms and then get upset when it rains.-AnonymousWe welcome the opinions of Balkrishna et al. on our multicenter study, which demonstrated a strong association of Tinospora cordifolia (Giloy) and autoimmune-like hepatitis. [1] The authors' arguments supporting the "safety" of Giloy come from multiple preclinical sources; these unpublished, non-peer-reviewed work have misinterpreted published data on Giloy, or the lack of it, to suit their narrative. They claim that 40 ml/day of Giloy was akin to an "overdose" and provide a misleading citation. In fact, their own product page and that of the Ministry of Ayush Guidelines on coronavirus disease 2019 mention a maximum daily dose of 60-80 ml/day. [2,3] Nonetheless, the authors' claims are fictitious, as the efficacy and safety Giloy for the prevention or mitigation of any disease condition in humans is not yet identified through robust clinical trials.Contrary to what Balkrishna et al. argue, our patients consumed properly identified Giloy and authentically marketed Giloy-based products, which were advertised and recommended via public and private Ayush promotions. The presence of a pre-existing liver condition does not exclude Giloy liver injury, but enforces the importance of diagnosing herb-induced acute worsening of chronic liver disease, which is known to be associated with high mortality. [4] The type, concentration, effective dose, safety limits, and toxicity of bio-active phytocompounds in Giloy products should ideally be disclosed by the manufacturer. The authors lay out irrational arguments leveraged on their confirmation biases, in support of the safety of Giloy, using various preclinical rat models. However, it is well known that animal models have sizeable limitations for predicting toxicity in human clinical trials. [5] Balkrishna et al. appeal to ignorance regarding livertoxic furano-diterpenoids, based on inaccurate citations that do not support their claims that these hepatotoxic compounds are lost during purification. The preparatory process for various Giloy-based formulations is not standardized. Nonetheless, they have missed the fact that Ayush Ministry guidelines explicitly state the use of aqueous-base extracted Giloy and not alcohol or chloroform processed decoctions.