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. Export

The reported burden of multidrug-resistant organism (MDRO) infections is highest in patients with cirrhosis from India. We evaluated whether colonisation at multiple barriers predisposes to such infections and poor outcomes in patients with cirrhosis. We prospectively performed swab cultures, antimicrobial susceptibility testing (AST), and genotype testing for MDROs from various sites (rectum, nose, composite-skin, and central-line) in patients with cirrhosis (2020–2021) on admission and follow-up at a tertiary institute. We analysed clinical data, risk factors for MDROs, and patient outcomes. Of 125 patients aged 49 years, 85.6% males, 60.8% with acute-on-chronic liver failure, 99 (79.2%) were identified as ‘colonisers’. MDRO-colonisation at rectum, nose, skin, or central line was observed in 72.7% (88/121), 30.0% (36/120), 14.9% (18/121), and 3.3% (4/121) patients, respectively. Patients were colonised with the following types of bacteria: extended-spectrum beta-lactamase (71/125), carbapenem-resistant Enterobacterales (67/125), MDR-Enterococcus (48/125), MDR-Acinetobacter (21/125), or methicillin-resistant Staphylococcus aureus (4/125). Multiple precipitants of acute-decompensation (odds ratio [OR]: 3.4, p = 0.042), norfloxacin prophylaxis (OR: 3.9, p = 0.008), and MDRO infection at admission (OR: 8.9, p = 0.041) were the independent predictors of colonisation. Colonisation increased the risk of infection by MDROs at admission (OR: 8.5, p = 0.017) and follow up (OR: 7.5, p <0.001). Although any-site colonisers were at greater risk of cerebral failure and poorer Child–Pugh scores, the nasal and skin colonisers were at higher risk of cerebral and circulatory failures than non-colonisers (p <0.05).Patients with more than one site colonisation (prevalence: 30%) developed multi-organ failure (p <0.05), MDRO infection (OR: 7.9, p <0.001), and poorer 30-day survival (hazard ratio: 2.0, p = 0.005). A strikingly high burden of MDRO colonisation among patients with cirrhosis in India necessitates urgent control measures. Multiple-site colonisation increases the risk of MDR-infections, multi-organ failure, and mortality in patients with cirrhosis. Infections by bacteria resistant to multiple antibiotics are an emerging cause of death in cirrhosis. We showed that ∼70–80% of critically ill hospitalised patients with cirrhosis carry such bacteria with the highest rate in the rectum, nose, skin, and central line port. Carbapenem-resistant and vancomycin-resistant bacteria were amongst the most common colonising bacteria. The presence of these bacteria at multiple sites increased the risk of multidrug-resistant infections, multiple organ failures, and death in patients with cirrhosis.

Hepatocellular carcinoma (HCC) is often recognized as an inflammation-linked cancer, which possesses an immunosuppressive tumor microenvironment. Curative treatments such as surgical resection, liver transplantation, and percutaneous ablation are mainly applicable in the early stage and demonstrate significant improvement of survival rate in most patients. However, 70–80% of patients report HCC recurrence within 5 years of curative treatment, representing an important clinical issue. However, there is no effective recurrence marker after surgical and locoregional therapies, thus, tumor size, number, and histological features such as cancer cell differentiation are often considered as risk factors for HCC recurrence. Host immunity plays a critical role in regulating carcinogenesis, and the immune microenvironment characterized by its composition, functional status, and density undergoes significant alterations in each stage of cancer progression. Recent studies reported that analysis of immune contexture could yield valuable information regarding the treatment response, prognosis and recurrence. This review emphasizes the prognostic value of tumors associated with immune factors in HCC recurrence after curative treatment. In particular, we review the immune landscape and immunological factors contributing to early-stage HCC recurrence, and discuss the immunotherapeutic interventions to prevent tumor recurrence following curative treatments.

INTRODUCTION: Hospitalized patients with acute decompensation (AD) of cirrhosis are at risk of progressing to acute-on-chronic liver failure (ACLF), significantly increasing their mortality. The aim of this study was to identify key predictors and patient trajectories predisposing to ACLF. METHODS: In this multicenter, prospective study spanning 2 years, clinical, biochemical, and 90-day survival data were collected from 625 patients with AD (European Association for the Study of the Liver criteria) across North, South, and East India. We divided the cohort into a Derivation cohort (DC: 318 patients) and a Validation cohort (VC: 307 patients). Predictive models for pre-ACLF were derived, validated, and compared with established scores such as model for end-stage liver disease (MELD) 3.0 and chronic liver failure Consortium acute decompensation. RESULTS: Of 625 patients (mean age 49 years, 83% male, 77.5% with alcohol-related liver disease), 32.2% progressed to ACLF. Patients progressing to ACLF showed significantly higher bilirubin (10.9 vs 8.1 mg/dL), leukocyte counts (9,400 vs 8,000 per mm³), international normalized ratio (1.9 vs 1.8), and MELD 3.0 (28 vs 25) but lower sodium (131 vs 134 mEq/L) and survival (62% vs 86%) compared with those without progression (P < 0.05) in the DC. Consistent results were noted with alcohol-associated hepatitis, infection and hepatic encephalopathy as additional risk factors in VC. Liver failure at presentation (odds ratio: 2.4 [in DC], 6.9 [in VC]) and the 7-day trajectories of bilirubin, international normalized ratio, and MELD 3.0 significantly predicted ACLF progression (P < 0.001). A new pre-ACLF model showed superior predictive capability (area under the curve of 0.71 in DC and 0.82 in VC) compared with MELD 3.0 and chronic liver failure Consortium acute decompensation scores (P < 0.05). DISCUSSION: Approximately one-third of AD patients in this Indian cohort rapidly progressed to ACLF, resulting in high mortality. Early identification of patients at risk can guide targeted interventions to prevent ACLF.