Clinical Research Directory

LiverTREM-1: Hepatic TREM-1 Expression and Prognosis in Severe Alcoholic Hepatitis

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