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Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20–33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732–0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713–0.775; p = 0.042) and Maddrey’s discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691–0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723–0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727–0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724–0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708–0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687–0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805–0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

Introduction and Objectives: Alcohol-associated hepatitis (AH) is a severe entity associated with high mortality. Corticosteroids might be used in cases with severe disease and several dynamic models can predict mortality and response to corticosteroids in AH patients. However, there is no consensus on the best of them. This study aimed to evaluate dynamic models to predict response to corticosteroid treatment based on short-term mortality in patients with severe AH based on a worldwide cohort. Materials and Methods: A retrospective cohort study of patients with severe AH (between 2009 – 2019). We included patients who received corticosteroid treatment and calculated the Lille model of day 4 (Lille-4), day 7 (Lille-7) (cut-off value ≥0.45), and the Trajectory of Serum Bilirubin (TSB)(cut-off value ≥0.8 of the ratio between bilirubin at admission and day 7) to predict mortality. We estimated up to 30-day survival using Kaplan-Meier curves, and we performed multivariable analyzes using Cox regression. Specifically, we constructed two models to compare Lille-4 vs. TSB and Lille-7 vs. TSB, adjusting by well-known clinical variables associated with higher mortality in AH (age, sex, and creatinine at admission). Results: 1,066 patients were included (30 centers, 10 countries), age 47.7 ± 10.9 years, 30% women. The MELD score on admission was 25 [21-30]. Responders were considered by Lille-4 49.1%, Lille-7 46.6%, and TSB 55.4%. In the first Cox regression, we observed that Lille-4 and TSB predicted 30-day mortality (HR 3.0, 95%CI: 1.7-5.1; p

Background: Cytomegalovirus (CMV) reactivation is known to occur among intensive care unit (ICU) patients. CMV-reactivation is not well-evaluated among critically ill cirrhotic adults who are not overtly immunocompromised. Objectives: Primary objective was to estimate the CMV-reactivation incidence rate among seropositive/latently infected critically ill cirrhotic adults. The secondary objective was to study the risk factors, host-related cytokine responses, and ICU outcomes associated with CMV-reactivation. Methods: In this longitudinal study conducted between November 2018 and June 2019, all consecutive anti-CMV-IgG-positive cirrhotic Liver-ICU patients were assessed at day 0/ICU-admission, day 7, 14, and 21 for CMV-reactivation/plasma-DNAemia (≥500 IU/ml), cytokines, clinical, laboratory and outcome parameters. Results: Fifty-five (48 male) cirrhosis patients consecutively admitted to liver-ICU were prospectively studied. Twenty (36%) adults developed CMV-reactivation. Majority (n=17/55, 30.9%; 95% CI: 19.1 - 44.8) showed CMV- reactivation on ICU-day 7. CMV-reactivation incidence rate during 21-day follow-up was 2.75% per person-day (95% CI: 1.68-4.26% per person-day). None of the risk factors studied was independently associated with CMV-reactivation. Acute respiratory distress syndrome (p=0.04), systemic inflammatory response syndrome (p=0.01), secondary (bacterial and/or fungal) infections (p=0.009), and raised pro-inflammatory cytokines (IFN γ, p=0.012; TNFα, p=0.052) were observed concomitantly to CMV-reactivation on ICU-day 7. ICU-Mortality (n=34/55, 61.8%) did not vary with a presence or absence of CMV-reactivation (55% versus 65.7%; p=0.43). Length of stay (LOS) in liver-ICU did not differ concerning CMV-reactivation (5 days versus 4.5 days; p=0.17) Conclusions: CMV-reactivation incidence rate was considerable among seropositive non-immunosuppressed critically ill cirrhotic adults. Mortality and LOS in Liver-ICU were not significantly influenced by CMV-reactivation.

Background: Acute viral hepatitis E (AVH-E) can often result in acute liver failure (ALF) during pregnancy. microRNAs serve as mediators in drug induced liver failure. We investigated their role as a biomarker in predicting ALF due to HEV (ALF-E). Methods: We performed next generation sequencing and subsequent validation studies in PBMCs of pregnant (P) self limiting AVH-E, ALF due to HEV (ALF-E) and compared with AVH-E in non-pregnant (NP) females and healthy controls. Findings: Eleven microRNAs were significantly expressed in response to HEV infection; importantly, miR- 431, 654, 1468 and 4435, were distinctly expressed in pregnant self-limiting AVH-E and healthy females (p = 0.0005), but not in ALF-E. Sixteen exclusive microRNAs differentiated ALF-E from self limiting AVH-E in pregnant females. miR-450b which affects cellular proliferation and metabolic processes through RNF20 and SECB was predominanlty upregulated and correlated with poor outcome (ROC 0.958, p = 0.001). Interpretation: Our results reveal that a specific microRNA profile can predict fatality in ALF-E in pregnancy. These microRNAs could be exploited as prognostic biomarkers and help in the development of new therapeutic interventions.

Introduction: Transfusion in cirrhotic patients remains a challenge due to the absence of evidence-based guidelines. Our study aimed to determine the indication of transfusion and the associated transfusion thresholds in cirrhotic patients. Methods: This retrospective observational study was conducted in the Department of Transfusion Medicine at a tertiary care liver center from October 2018 to March 2019. The blood bank and patient records of cirrhotic patients admitted during the study period were retrieved and analyzed to determine the current transfusion practice. Results: A total of 992 cirrhotic patients were included in the study. Blood components were transfused to 402 (40.5%) patients. Sixty-nine (17.2%) patients were transfused to control/treat active bleeding, while 333 (82.8%) were transfused prophylactically. Packed red blood cells (65.4%) was the most commonly transfused blood component, followed by fresh frozen plasma (35.6%), among patients receiving transfusions (therapeutic & prophylactic). The mean pre-transfusion thresholds for: (i) packed red blood cell transfusion: hemoglobin less than 7 g/dL; (ii) fresh frozen plasma transfusion: international normalized ratio over 2.6; (iii) platelet concentrate transfusion: platelet count less than 40,700/μL, and; (iv) cryoprecipitate transfusion: fibrinogen less than 110 mg/dL. The average length of stay of the study population was 5 days (3–9). Conclusion: To conclude, 40.5% of our hospitalized cirrhotic patients were transfused, with the majority of the transfusions being prophylactic (82.8%). Separate guidelines are required for this patient population, as these patients have an altered hemostasis which responds differently to the transfusion of blood components.

Background & Aims: Endothelial injury and dysfunction play a detrimental role in the pathogenesis of infections. Endothelium-related molecules have been reported as potential diagnostic and/or prognostic biomarkers of infection. The prognostic value of these biomarkers in patients with cirrhosis and infections remains elusive. Methods: In this study, we investigated the performance of key soluble endothelial injury biomarkers, including intercellular adhesion molecule 1 (ICAM1), von Willebrand factor (vWF), vascular endothelial growth factor receptor 1 (VEGFR1), and angiopoietin 1 and 2 (Ang1, 2) as mortality predictors in patients with cirrhosis and severe COVID-19 or bacterial sepsis. Results: A total of 66 hospitalized patients (admitted to the COVID-19 ward or liver intensive care unit [ICU]) were included. Twenty-two patients had COVID-19 alone, while 20 patients had cirrhosis plus COVID-19. Twenty-four patients had cirrhosis plus bacterial sepsis. Among patients with cirrhosis, the most common aetiology of liver disease was alcohol. ICAM1 was increased (p = 0.003) while VEGFR1 (p