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Alcohol-related liver disease (ALD) encompasses a spectrum of diseases caused by excessive alcohol consumption. ALD includes hepatic steatosis, steatohepatitis, variable degrees of fibrosis, cirrhosis, and alcohol-associated hepatitis (AH), the latter being the most severe acute form of the disease. Severe AH is associated with high mortality (reaching up to 30%–50%) at 90 days. The cornerstone of ALD, and particularly AH, treatment continues to be abstinence, accompanied by support measures such as nutritional supplementation and management of alcohol withdrawal syndrome (AWS). In severe AH with model for end-stage liver disease (MELD) score ≥21, corticosteroids can be used, especially MELD score between 25 and 39, where the highest benefit is achieved. Other key aspects of treatment include the early identification of infections and their associated management and the proper identification of potential candidates for liver transplantation. The development of new therapies based on the pathophysiology and mechanisms of liver injury are underway. This includes the modulation and management of the innate immune response, gut dysbiosis, bacterial translocation, and bacteria-derived products from the intestine. These hold promise for the future of AH treatment.

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

Introduction and Objectives: Severe alcohol-associated hepatitis (AH) is an entity with high morbidity and mortality; however, data in Latin America is limited. We aimed to characterize patients hospitalized for AH in a multinational cohort in Latin America. Materials and Methods: Multicenter prospective cohort study. We included patients admitted with severe AH between 2015-2022. Sociodemographic and clinical information was recorded. The analysis included survival analysis using Kaplan-Meier curves. This study was approved by the institutional ethics committee. Results: 470 patients from 24 centers (8 countries: Mexico, Chile, Argentina, Brazil, Peru, Bolivia, Colombia, and Ecuador) were included. Age 49.8 ± 10.6 years, 85.6% of men and 45% had a previous diagnosis of cirrhosis. Median MELD at admission was 26.9 [22-32] points. 26.5% met SIRS criteria and 34.3% had an acute kidney injury (AKI) on admission. Only 36.8% of patients were treated with corticosteroids. Survival at 30 days was 75.0% (95%CI: 70.1-79.3%) and 62.8% (95%CI: 57.1-68.0%) at 90 days. A total of 191 (45.8%) patients presented infections, 31.4% at admission and 24.9% during hospitalization. The most frequent locations of community-acquired infections were respiratory (33.5%), urinary (32.1%), spontaneous bacterial peritonitis (14.9%), and skin (10.5%), while the most frequent pathogens were Escherichia coli (40%), Klebsiella pneumoniae (12%), and Enterococcus (6%). The presence of infection at admission was associated with a decreased survival at 90-days (66.9% versus 48.1%, p=0.0002). AKI at admission was also associated with decreased survival at 90-days (86.8% versus 51.3%, p

In hepatorenal syndrome-acute kidney injury (HRS-AKI), accurate and early diagnosis is crucial. HRS is a severe condition seen in advanced cirrhosis, requiring prompt recognition and proper management to enhance patient outcomes. Diagnosis of HRS-AKI relies on serum creatinine elevations, similar to other AKI cases in cirrhosis. However, distinguishing HRS-AKI from other renal impairments in these patients can be challenging. Biomarkers and clinical criteria aid in diagnosis and guide treatment. The management of HRS-AKI initially involves improving the haemodynamic profile using albumin and vasoconstrictors like terlipressin, a synthetic vasopressin analogue. Despite some reports linking terlipressin to increased adverse events compared with norepinephrine, it remains the preferred choice in HRS-AKI and acute-on-chronic liver failure due to its faster, stronger response and improved survival. Additional therapies like midodrine (alpha-1 adrenergic agonist), octreotide (somatostatin analogue) and transjugular intrahepatic portosystemic shunt are proposed as adjuvant treatments for HRS-AKI, aiming to improve vasoconstriction and renal blood flow. However, these adjunctive therapies cannot replace the definitive treatment for HRS-AKI—liver transplantation (LT). In cases unresponsive to medical management, LT is the only option to restore liver function and improve renal outcomes. Current evidence favours combined liver and kidney transplantation (CLKT) in certain situations. This review aims to evaluate the present evidence and recommendations on AKI in patients with cirrhosis, the pathophysiology of HRS-AKI, different treatments and indications for LT and CLKT. Understanding the complexities of managing HRS-AKI is crucial for optimising patient care and achieving better outcomes in this challenging clinical setting.