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

Summary

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

Conditions

• Severe Alcoholic Hepatitis

Interventions

DIAGNOSTIC_TEST

TREM-1 expression (via immunohistochemistry) between SAH patients and controls

this is the first study to focus on hepatocyte-specific TREM-1 expression in human liver tissue What Distinguishes This Study Tissue-Level Focus: Unlike most studies that assess blood biomarkers or systemic inflammation, this research directly measures TREM-1 expression in liver tissue (hepatocytes), offering localized insights into disease severity and immune response. Retrospective Biobank Utilization: Leverages a rich biobank of archival biopsies spanning 10 years, ensuring real-world data and long-term clinical follow-up-rarely combined at this scale in similar research. Dual Purpose (Diagnostic \& Prognostic): Most biomarkers are evaluated for either diagnostic or prognostic value-this study uniquely addresses both in a single, comprehensive framework. Therapeutic Translation Potential: TREM-1 is already a target for pharmacological inhibition (e.g., with peptide inhibitors tested safely in humans for other conditions). This positions the study for rapid clinical translation,

Sponsors & Collaborators

• Central Hospital, Nancy, France

  lead OTHER

Principal Investigators

• Vincent Haghnejad, MD · CHRU de Nancy

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-10-01

Primary Completion

2026-10-31

Completion

2026-12-31