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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

Abstract A primary limitation in hepatic surgery is leaving a remnant liver of adequate size and function. Experimental models have been designed to study processes of liver injury and regeneration in this context, yet a formula to accurately calculate liver mass in an animal model is lacking. This study aims to create a novel and simple formula to estimate the mass of the native liver in a species of pigs commonly used in experimental liver surgery protocols. Using data from 200 male weanling Landrace-Large White hybrid pigs, multiple linear regression analysis is used to generate the formula. Clinical features used as variables for the predictive model are body mass and length. The final formula for pig liver mass is as follows: Liver mass (g) = 26.34232 * Body mass (kg) – 1.270629 * Length (cm) + 163.0076; R2 = 0.7307. This formula for porcine liver mass is simple to use and may be helpful in studies using animals of similar characteristics to evaluate restoration of liver mass following major hepatectomy.

Abstract In this study, we investigated the role of CD38 in a pristane-induced murine model of lupus. CD38-deficient (Cd38 −/−) but not ART2-deficient (Art2 −/−) mice developed less severe lupus compared to wild type (WT) mice, and their protective phenotype consisted of (i) decreased IFN-I-stimulated gene expression, (ii) decreased numbers of peritoneal CCR2hiLy6Chi inflammatory monocytes, TNF-α-producing Ly6G+ neutrophils and Ly6Clo monocytes/macrophages, (iii) decreased production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv) ameliorated glomerulonephritis. Cd38 −/− pristane-elicited peritoneal exudate cells had defective CCL2 and TNF-α secretion following TLR7 stimulation. However, Tnf-α and Cxcl12 gene expression in Cd38 −/− bone marrow (BM) cells was intact, suggesting a CD38-independent TLR7/TNF-α/CXCL12 axis in the BM. Chemotactic responses of Cd38 −/− Ly6Chi monocytes and Ly6G+ neutrophils were not impaired. However, Cd38 −/− Ly6Chi monocytes and Ly6Clo monocytes/macrophages had defective apoptosis-mediated cell death. Importantly, mice lacking the cation channel TRPM2 (Trpm2 −/−) exhibited very similar protection, with decreased numbers of PECs, and apoptotic Ly6Chi monocytes and Ly6Clo monocytes/macrophages compared to WT mice. These findings reveal a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via an apoptosis-driven mechanism. Furthermore, given the implications of CD38 in the activation of TRPM2, our data suggest that CD38 modulation of pristane-induced apoptosis is TRPM2-dependent.

The burden of alcoholic liver disease continues to be a major public health problem worldwide. The spectrum of disease ranges from fatty liver to cirrhosis and hepatocellular carcinoma. Alcoholic hepatitis (AH) is a type of acute-on-chronic liver failure and the most severe form of alcoholic liver disease. Severe AH carries a poor short-term prognosis and its management is still challenging, with scarce advances in the last decades. Corticosteroids are still the first line of therapy in severe cases. Unfortunately, many patients do not respond and novel targeted therapies are urgently needed. Liver transplantation has shown extraordinary results in non-responders to corticosteroids however; its applicability is very low. This review summarizes the epidemiology, natural history, risk factors and pathogenesis of alcoholic liver disease with special focus on the latest advances in prognostic stratification and therapy of patients with alcoholic hepatitis.