Chundamannil Eapen Eapen

Background: Acute liver dysfunction may impair sedative drug metabolism in the liver and lead to sedative overdose, leading to drowsiness, respiratory depression, and contributing to mortality. This study aims to analyze the use of sedatives in patients with rodenticidal hepatotoxicity. Materials and Methods: Details of sedative use and inhospital outcomes were studied from inpatient records of patients with rodenticidal ingestion admitted under department of Hepatology (2014–2021). Results: Of 114 patients with rodenticidal hepatotoxicity, the worst clinical syndrome during the hospital stay was acute liver injury in 73 (64%) and acute liver failure in 41 (36%), with the worst MELD being 29 (6–50) (median, range). No patient underwent liver transplantation. 25/114 (22%) patients received sedatives (all intravenously) – dexmedetomidine (nine patients), midazolam (9), haloperidol (9), lorazepam (5) and fentanyl (5). Indications for sedative use: agitation (19), endotracheal intubation (12). All received standard doses of sedatives. 15/25 (60%) patients who received sedatives had worsening oxygen saturation and worsening sensorium, and all 15 patients died. Mortality was significantly higher in patients with sedative use (15/25, 60%) as compared to patients with no sedative use (9/89, 10.1%) ( P < 0.001). Of 21 patients who had low sensorium at admission, there was only 1 death in 8 patients (12.5%) who did not receive sedatives compared to 8/13 (61.5%) deaths in those who received sedatives. Conclusion: Most (79%) rodenticidal hepatotoxicity patients were managed without sedatives in this analysis. Sedative use was associated with respiratory depression, worsening sensorium, and increased risk of death. Our study findings suggest the “restricted sedative use” policy of Tamil Nadu Government – National Health Mission Guidelines to manage rodenticidal hepatotoxicity patients may improve native liver survival.

Plasma exchange (PLEX) improves survival in acute liver failure (ALF); however, there is no study specifically analyzing its utility in hepatitis A virus-related ALF (HAV-ALF). A few reports suggest that ALF patients who are not on inotropes tolerate PLEX better. We aimed at comparing the efficacy of PLEX and of standard medical treatment (SMT) to treat HAV-ALF. We retrospectively compared consecutive HAV-ALF patients treated with PLEX (2018-2024) vs. SMT (2011-2024) at 13 centers across India. We compared in-hospital native liver survival in both groups. In the subset of patients not on inotropes, we compared survival and assessed predictors of poor outcome in PLEX and SMT groups. Eighty-four HAV-ALF patients in PLEX group (61 males; age = 23.5 [21-33] years, median [IQR]; King's College Criteria [KCC] fulfilled = 22 patients, 26.2%) and 150 HAV-ALF in SMT group (101 males; 24 [19-32.3] years; KCC fulfilled = 16, 10.7%) were studied. Overall survival was comparable in PLEX (70.2%) and SMT groups (65.3%) (p-value = 0.47). In a sub-group of hemodynamically stable patients not on inotropes, univariate analysis showed better survival in PLEX group (52/54, 96.3%) as compared to SMT group (81/104, 77.9%; OR = 0.135, 95% CI = 0.03-0.6; p-value = 0.002). However, this benefit was not noted in propensity score matched/regression analyses. While PLEX did not influence in-hospital outcome across all HAV-ALF patients, it may confer survival benefit in a sub-group who remained hemodynamically stable not requiring inotropes. Studies with larger patient numbers are needed to explore this hypothesis.

INTRODUCTION: Nosocomial infections (NIs) in cirrhosis are associated with high mortality but could be preventable. Logistic regression (LR) models have failed to identify high-risk patients. We aimed to develop machine learning (ML) models to predict NI. METHODS: The CLEARED consortium consists of prospectively enrolled cirrhosis inpatients from >120 centers. Using day-of-admission clinical data, 3 ML approaches (random forest [RF], extreme gradient boosting, and neural networks [NNs]) were used to predict NI. Data were split 80:20 for training and testing stratified by the outcome. Models were compared using area under the receiver operating characteristic curve (AUC). RESULTS: In total, 8,263 patients (55.90 ± 13.34 years; 64.1% men) from 127 centers in 37 countries were included. NI developed in 869 (10.5%), a median of 6 (4–11) days of postadmission. Major NIs were respiratory (29.6%) and urinary tract infection (15.7%), and spontaneous bacterial peritonitis (13.5%). NIs occurred more frequently in patients from low/low-middle income countries and those with severe liver disease, alcohol etiology, and admission infections. NIs were associated with inpatient mortality (31.9% vs 8.1%, P < 0.001) and liver transplantation (4.8% vs 1.9%, P < 0.001). Although the RF model (AUC 0.69) showed good calibration (Brier score 0.09), outperforming extreme gradient boosting, neural network, and LR models (AUC 0.66 for all; LR comparison P = 0.043), no model achieved AUC ≥0.80 for clinical utility. At 10% predicted probability threshold, the RF model demonstrated only 75.4% sensitivity, 52.9% specificity, and 15.9% positive predictive value (PPV). DISCUSSION: NIs cannot be accurately predicted from day-of-admission data using ML models, even in a large, prospective, global cirrhosis cohort. Every hospitalized patient with cirrhosis should receive protocolized infection control measures.

Background Acute-on-chronic liver failure (ACLF) is a rapidly progressive syndrome marked by high short-term mortality. While diabetes mellitus (DM) is known to worsen liver-related outcomes, its specific impact on alcohol-related ACLF (ALD-ACLF) remains underexplored. This study aimed to assess the prognostic impact of DM on 90-day outcomes in ALD-ACLF using data from the APASL ACLF Research Consortium (AARC) database. Methods This observational study involved data from 5612 ACLF patients with documented 90-day outcomes. We identified 2096 patients with ALD-ACLF precipitated by alcoholic hepatitis. Patients with non-ALD etiologies, mixed etiologies, or non-alcoholic precipitants were excluded. Diabetic and non-diabetic patients were compared using 1:2 propensity score matching based on key baseline covariates. Survival outcomes were assessed using Kaplan–Meier analysis and multivariable Cox regression. Results After matching, 109 diabetic patients were compared with 218 well-matched non-diabetic controls. Diabetic patients had significantly lower overall survival (32 vs. 57%) and transplant-free survival (31 vs. 50%) compared to non-diabetics (log-rank p < 0.001). On multivariable Cox regression, DM was independently associated with increased 90-day mortality (HR 1.739, 95% CI 1.262–2.395, p < 0.001), along with elevated serum lactate (HR 1.187 per mmol/L, p < 0.001) and creatinine (HR 1.267 per mg/dL, p < 0.001). Conclusion Diabetes mellitus is a significant independent predictor of mortality in patients with ALD-ACLF. These findings highlight the need for early identification and integrated management of diabetes in ACLF care pathways to improve clinical outcomes.

Objective Severe alcohol-associated hepatitis (AAH) driven acute-on-chronic liver failure (ACLF) carries high short-term mortality, where corticosteroids offer limited benefit. This study evaluated the safety and impact of therapeutic plasma exchange (PLEX) in this setting. Design/method This prospective multicentre study included adults with severe AAH precipitating Asian Pacific Association for the Study of the Liver (APASL)-defined ACLF who received PLEX across 12 tertiary hospitals in Tamil Nadu, India. The primary outcome was 1-month transplant-free survival. Secondary outcomes included changes in disease severity scores after PLEX, survival predictors and adverse events. Results Over 3 months (June–August 2024), 51 patients (98% male, mean age 44 years) underwent PLEX; none received corticosteroids beforehand. 1-month transplant-free survival was 78.4%. Most patients (88.2%) received early PLEX (≤5 days from hospital admission); 74.5% received low-volume PLEX. Low-dose corticosteroids were used with PLEX in 82.4%. Post-PLEX, disease severity scores declined significantly (mean Model for End-Stage Liver Disease (MELD): 31.6 to 26.5; APASL ACLF Research Consortium (AARC): 10.2 to 8.4; both pConclusions PLEX with low-dose steroids was safe and feasible in AAH-related ACLF. Post-PLEX AARC score predicted 1-month mortality. Greater declines in disease severity scores among survivors suggest their role as early response markers. These findings support further prospective evaluation of PLEX in AAH-related ACLF.

Introduction: Acute‐on‐chronic liver failure (ACLF) is associated with immune dysregulation, characterized by simultaneous inflammation and immune suppression. Alcohol‐related ACLF (A‐ACLF) has particularly high mortality, yet the role of monocyte dysfunction and plasma‐derived inflammatory mediators remains poorly understood.Methods: A prospective study was conducted from July 2019 to May 2020, recruiting A‐ACLF patients and healthy controls. Monocyte phenotyping and serum immune markers (sCD163, sCD25, ferritin, and IgG immune complexes) were measured. Ex vivo plasma priming experiments were performed on healthy monocytes, and cytokine production was measured.Results: A‐ACLF patients (n = 25, median [min–max] age: 42 [23–64] years, 24 males) showed higher proportions (12.5 [3.47–41.8] vs. 2.98 [0.62–8.89]) and counts of monocytes (counts/μL: 229 [48–1505] vs. 82 [22–250]), with increased classical and reduced patrolling monocyte subsets correlating with higher MELD scores (r = 0.48, p = 0.05) and poor outcomes. A‐ACLF monocytes showed increased Fc receptor expression (CD64 MFI: 4648 [2214–7819] vs. 1834 [168–3221]), suggesting monocyte hyperactivation and responsiveness to immune complexes, and lower HLA‐DR expression (MFI 444 [133–1147] vs. 916 [451–2067]), indicating immune exhaustion. Increased expression of the liver‐homing receptor CCR2 was noted in classical monocytes. Healthy human peripheral monocytes cultured with A‐ACLF plasma showed upregulated CCR5 and downregulated CD14, suggesting effects on monocyte trafficking and differentiation. Monocytes primed with A‐ACLF plasma secreted higher TNF‐α, IL‐1β, IL‐12, and G‐CSF, indicating plasma‐driven inflammation.Conclusion: Our findings reveal monocyte dysfunction and plasma‐induced immune alterations as key contributors to A‐ACLF pathogenesis and prognosis. Targeting plasma‐derived inflammatory mediators may offer novel therapeutic strategies.