Severe Alcoholic Hepatitis

Alcoholic hepatitis carries a risk of high mortality at short term, especially in its severe form. Its diagnosis is confirmed by liver biopsy. The prevalence of alcoholic hepatitis, severe or not severe, is poorly known and prospective data are needed. The present observational study aims to define the prevalence of alcoholic hepatitis among patients admitted for jaundice and determine their outcome according to the severity. Survival and markers of liver dysfunction will be assessed. A biobank including genetic samples will be created to identify the disease profile in terms of inflammation and regeneration. The performance of non-invasive criteria for diagnosis will also be studied.

Background \& Rationale Severe alcohol-related hepatitis (SAH) is a serious condition with a 3-month mortality rate of \~30%. Diagnosis and prognosis are complex due to non-specific and insensitive clinical, biological, and histological indicators. Corticosteroids-the only validated treatment-are only effective in 50% of cases and can worsen outcomes in non-responders by promoting infections. Liver transplantation remains a limited option due to organ scarcity and patient eligibility. TREM-1, a pro-inflammatory receptor, has shown promise in inflammatory liver diseases. Its expression in hepatocytes may serve as a biomarker to better classify patients, guide treatment, and improve outcomes. Objectives Primary Objective: Compare TREM-1 expression (via immunohistochemistry) between SAH patients and controls with other liver diseases (e.g., HCC, metastatic colon cancer, cholangiocarcinoma). Secondary Objectives: Determine optimal antibody dilution for TREM-1 staining. Assess diagnostic performance (sensitivity, specificity, PPV, NPV). Identify homogeneous SAH subgroups using clinical, histological, and biological data. Evaluate prognostic value of TREM-1 expression for: 2-month mortality Corticosteroid response (bilirubin regression at Day 7) Lille score \<0.45 at Day 7 Compare TREM-1's predictive power to standard scores (MELD, Maddrey, Lille, etc.). Methodology Population: Cases: Adults treated at CHRU de Nancy (2013-2023) for SAH, with archived liver biopsies. Controls: Adults with liver malignancies and archived biopsies. Sample Size: Phase I: 12 cases, 6 controls Phase II: 150 cases, 150 controls Data Sources: Medical records, archived pathology slides Statistical Tools: Logistic regression, survival analysis, ROC curves, clustering, SAS/R software Expected Outcomes \& Impact Improved prognostic stratification and therapeutic guidance for SAH patients Better targeting of corticosteroid therapy to reduce unnecessary risk Early referral for liver transplantation when appropriate Validation of TREM-1 as a diagnostic/prognostic biomarker Foundation for future TREM-1-targeted clinical trials Potential paradigm shift linking liver histology with real-time clinical decision-making Enhanced resource allocation and patient management