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

NCT07176741 | Not Yet Recruiting DMC

• 1 other identifier: 2023PI101
• Study Type: observational
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief 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

Keywords

TREM-1; sAH; biomarker; prognosis; alcoholic hepatitis; alcohol use disorder; AUD; cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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).

  Day 0 index liver biopsy

Secondary Outcomes (1)

• Baseline TREM-1 expression (via RNAseq3') in patients with severe alcohol-associated hepatitis (SAH)

  Day 0 (index liver biopsy)

Study Arms (1)

Biopsy-proven severe alcoholic hepatitis and control liver specimens

Cases: Adults treated at CHRU de Nancy (2013-2023) for Severe Alcoholic Hepatitis, with archived liver biopsies. Controls: Adults with liver malignancies and archived biopsies.

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

Interventions

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

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,

Biopsy-proven severe alcoholic hepatitis and control liver specimens

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Cases:
• 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.
• Controls:
• Individuals who received full information about the study and did not object to the use of their data within this research.
• Patients treated and operated on at CHRU de Nancy for hepatocellular carcinoma, colorectal cancer liver metastasis, or cholangiocarcinoma between January 1, 2013, and December 31, 2023.
• Archived liver biopsy slides available at CHRU de Nancy.
• Adult patients at the time of diagnosis.

You may not qualify if:

• None

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Related Publications (6)

• Duan M, Wang ZC, Wang XY, Shi JY, Yang LX, Ding ZB, Gao Q, Zhou J, Fan J. TREM-1, an inflammatory modulator, is expressed in hepatocellular carcinoma cells and significantly promotes tumor progression. Ann Surg Oncol. 2015 Sep;22(9):3121-9. doi: 10.1245/s10434-014-4191-7. Epub 2014 Dec 3.

  PMID: 25465376 BACKGROUND

• Ichou L, Carbonell N, Rautou PE, Laurans L, Bourcier S, Pichereau C, Baudel JL, Nousbaum JB, Renou C, Anty R, Tankovic J, Maury E, Guidet B, Landraud L, Ait-Oufella H. Ascitic fluid TREM-1 for the diagnosis of spontaneous bacterial peritonitis. Gut. 2016 Mar;65(3):536-8. doi: 10.1136/gutjnl-2015-310160. Epub 2015 Jul 3. No abstract available.

  PMID: 26141143 BACKGROUND

• Francois B, Lambden S, Garaud JJ, Derive M, Grouin JM, Asfar P, Darreau C, Mira JP, Quenot JP, Lemarie J, Mercier E, Lacherade JC, Vinsonneau C, Fivez T, Helms J, Badie J, Levy M, Cuvier V, Salcedo-Magguilli M, Laszlo-Pouvreau AL, Laterre PF, Gibot S; ESSENTIAL investigators. Evaluation of the efficacy and safety of TREM-1 inhibition with nangibotide in patients with COVID-19 receiving respiratory support: the ESSENTIAL randomised, double-blind trial. EClinicalMedicine. 2023 Jun;60:102013. doi: 10.1016/j.eclinm.2023.102013. Epub 2023 May 31.

  PMID: 37350989 BACKGROUND

• Francois B, Lambden S, Fivez T, Gibot S, Derive M, Grouin JM, Salcedo-Magguilli M, Lemarie J, De Schryver N, Jalkanen V, Hicheur T, Garaud JJ, Cuvier V, Ferrer R, Bestle M, Pettila V, Mira JP, Bouisse C, Mercier E, Vermassen J, Huberlant V, Vinatier I, Anguel N, Levy M, Laterre PF; ASTONISH investigators. Prospective evaluation of the efficacy, safety, and optimal biomarker enrichment strategy for nangibotide, a TREM-1 inhibitor, in patients with septic shock (ASTONISH): a double-blind, randomised, controlled, phase 2b trial. Lancet Respir Med. 2023 Oct;11(10):894-904. doi: 10.1016/S2213-2600(23)00158-3. Epub 2023 May 31.

  PMID: 37269870 BACKGROUND

• Francois B, Wittebole X, Ferrer R, Mira JP, Dugernier T, Gibot S, Derive M, Olivier A, Cuvier V, Witte S, Pickkers P, Vandenhende F, Garaud JJ, Sanchez M, Salcedo-Magguilli M, Laterre PF. Nangibotide in patients with septic shock: a Phase 2a randomized controlled clinical trial. Intensive Care Med. 2020 Jul;46(7):1425-1437. doi: 10.1007/s00134-020-06109-z. Epub 2020 May 28.

  PMID: 32468087 BACKGROUND

• Mathurin P, Duchatelle V, Ramond MJ, Degott C, Bedossa P, Erlinger S, Benhamou JP, Chaput JC, Rueff B, Poynard T. Survival and prognostic factors in patients with severe alcoholic hepatitis treated with prednisolone. Gastroenterology. 1996 Jun;110(6):1847-53. doi: 10.1053/gast.1996.v110.pm8964410.

  PMID: 8964410 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

histological staining

MeSH Terms

Conditions

Hepatitis, Alcoholic; Alcoholism; Fibrosis

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Vincent Haghnejad, MD

  CHRU de Nancy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vincent HAGHNEJAD, MD

CONTACT

+33383153354; v.haghnejad@chru-nancy.fr

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: June 15, 2025
• First Posted: September 16, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share