Ashwagandha-induced liver injury-A case series from India and literature review.

BACKGROUND: Ashwagandha herb is commonly used in Ayurveda and a "fad" dietary supplement for a host of indications based on low levels of evidence. Recently, ashwagandha was implicated in multiple reports of herb-induced liver injury (HILI), mainly from the United States. We present the first, and currently largest, series of ashwagandha-HILI from multiple centers in India. METHODS: We retrospectively analyzed the respective institutional electronic medical records for ashwagandha-HILI. Patients consuming ashwagandha as part of multiherbal formulations or along with other known hepatotoxic supplements or medicines were excluded. All patients underwent a detailed diagnostic workup to exclude competing causes reasonably. Where possible, the implicated herbal formulation was retrieved and subjected to chemical analysis. RESULTS: Out of 23 patients with liver injury from ashwagandha (January 2019 to December 2022), we report 8 patients with single-ingredient formulation-related HILI. Study cohort was male predominant, and cholestatic hepatitis was the commonest presentation. Five patients had underlying chronic liver disease; 3 presented with acute-on-chronic liver failure, and all 3 died on follow-up. In others, the liver injury was prolonged, nonetheless self-limiting. Liver biopsy revealed cholestatic features predominantly with hepatocellular necrosis and lymphocyte/eosinophil predominant portal-based inflammation. One patient progressed to chronic HILI. Chemical analysis revealed only natural phytochemicals without adulteration or contamination. CONCLUSIONS: Ashwagandha-HILI presents with cholestatic hepatitis and can lead to the syndrome of acute-on-chronic liver failure with high mortality in those with pre-existing liver disease. Educating the public on avoiding the use of potentially toxic and unrecommended herbal supplements can help mitigate the avoidable liver disease burden in the community.

Tinospora Cordifolia (Giloy)-Induced Liver Injury During the COVID-19 Pandemic-Multicenter Nationwide Study From India.

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.

Acute upper gastrointestinal bleed: An audit of the causes and outcomes from a tertiary care center in eastern India.

BACKGROUND/PURPOSE OF THE STUDY: Acute upper gastrointestinal (UGI) bleed is a life-threatening emergency carrying risks of rebleed and mortality despite standard pharmacological and endoscopic management. We aimed to determine etiologies of acute UGI bleed in hospitalized patients and outcomes (rebleed rates, 5-day mortality, in-hospital mortality, 6-week mortality, need for surgery) and to determine predictors of rebleed and mortality. METHODS: Clinical and endoscopic findings were recorded in patients aged > 12 years who presented within 72 h of onset of UGI bleed. Outcomes were recorded during the hospital stay and 6 weeks after discharge. RESULTS: A total of 305 patients were included in this study, mean age being 44 ± 17 years. Most common etiology of UGI bleed was portal hypertension (62.3%) followed by peptic ulcer disease (PUD) (16.7%). Rebleed rate within 6 weeks was 37.4% (portal hypertension 47.9%, PUD 21.6%, malignancy 71.4%). Five-day mortality was 2.3% (malignancy 14.3%, portal hypertension 3.2%); the in-hospital mortality rate was 3.0% (malignancy 14.3%, portal hypertension 3.2%, PUD 0.0%) and 4.9% at 6 weeks (malignancy 28.6%, portal hypertension 5.8%, PUD 0.0%). Surgery was required in 4.59% patients. On multivariate analysis, post-endoscopy Rockall score was significantly predictive of rebleed in both portal hypertension- and PUD-related rebleed. No factors were found predictive of mortality in multivariate analysis. CONCLUSION: Portal hypertension remains the commonest cause of UGI bleed in India and carries a higher risk of rebleed and mortality as compared to PUD-related bleed. Post-endoscopy Rockall score is a useful tool for clinicians to assess risk of rebleed.