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
Individuals who received full information about the study and did not object to the use of their data within this research.
Patients managed in one of the intensive care or hepatogastroenterology departments at CHRU de Nancy for severe alcohol-related hepatitis between January 1, 2013, and December 31, 2023.
Archived liver biopsy slides available at CHRU de Nancy.
Adult patients at the time of diagnosis.
None
Case: Adult patient managed in one of the intensive care or hepatogastroenterology departments at CHRU de Nancy for severe alcohol-related hepatitis between January 1, 2013, and December 31, 2023, inclusive. Control: Adult patient managed and operated on at CHRU de Nancy for hepatocellular carcinoma, colorectal cancer liver metastasis, or cholangiocarcinoma between January 1, 2013, and December 31, 2023, inclusive.
Case-control
Retrospective
TREM-1 expression (via immunohistochemistry) between SAH patients and controls
Diagnostic testthis 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,
Baseline Hepatocyte TREM-1 expression in SAH patients vs. controls on the day of biopsy
Compare hepatocyte TREM-1 expression (via immunohistochemistry) in patients with severe alcohol-associated hepatitis (SAH) versus controls with other liver diseases (e.g., hepatocellular carcinoma, colorectal liver metastases, cholangiocarcinoma). TREM-1 expression is scored as high or low using a validated semi-quantitative method. Unit of Measure: Median hepatocyte TREM-1 H-score \[IQR\] Archival liver specimens obtained Jan 1, 2013-Dec 31, 2024 were used; assessment reflects baseline (the day of the biopsy).
Baseline TREM-1 expression (via RNAseq3') in patients with severe alcohol-associated hepatitis (SAH)
Compare hepatocyte TREM-1 expression (via RNAseq3') in patients with severe alcohol-associated hepatitis (SAH). TREM expression is normalized according to sequencing depth and gene length. Median hepatocyte TREM-1 \[IQR\] or mean +/- \[SD\] and Binary detection of hepatocyte TREM-1 by 3' RNA-seq. Expressor (Detected) = normalized transcript value \> 0 (e.g., FPM \> 0); Non-expressor (Not detected) = 0. RNA was extracted from tissue taken at the baseline biopsy; archival specimens span Jan 1, 2013-Dec 31, 2024.
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