Severe Alcoholic HepatitisLiver TREM-1NCT07176741
LiverTREM-1: Hepatic TREM-1 Expression and Prognosis in Severe Alcoholic Hepatitis
An observational study of Severe Alcoholic Hepatitis, run by Central Hospital, Nancy, France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Alcoholic Hepatitis
- How many people
- 300 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2025to Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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:
Show all 10Show fewer
- 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.
Who cannot join
- None
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Measurement of Hepatocyte TREM-1 Expression Level to Evaluate Its Intrinsic Performance and Prognostic Value in Severe Symptomatic Alcohol-related 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.
Read more
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
Read the detailed description
Study Title
Official Title:
Liver TREM-1: Hepatic Expression of TREM-1 in Severe Alcoholic Hepatitis
Brief Summary (250 words max) Severe alcohol-associated hepatitis (sAH) is a life-threatening liver disease with a 3-month mortality rate of up to 30%. The only validated treatment-corticosteroids-fails in approximately 40% of patients, increases infection risk, and offers no survival benefit beyond 28 days. Therefore, there is an urgent need to identify prognostic biomarkers to guide therapy.
TREM-1 (Triggering Receptor Expressed on Myeloid cells 1) is a pro-inflammatory receptor expressed on hepatic immune and endothelial cells. Preclinical murine studies suggest it plays a pivotal role in alcohol-induced liver injury. This observational study aims to assess the diagnostic and prognostic value of hepatic TREM-1 expression in patients with severe alcohol-associated hepatitis using archived liver biopsy samples.
A total of 300 archived liver specimens (150 sAH cases, 150 controls with hepatic malignancies) will be analyzed via immunohistochemistry using a validated TREM-1 scoring system. Outcomes include TREM-1 expression levels, correlation with clinical parameters, mortality at 2 months, and response to corticosteroid therapy.
Detailed Description The study will determine whether hepatic TREM-1 expression can serve as a biomarker to stratify sAH patients into prognostic subgroups. TREM-1 expression will be measured via immunostaining and categorized as high vs. low using a score developed by Duan et al. Secondary analyses include diagnostic accuracy, treatment response (based on jaundice regression and Lille score at Day 7), and survival at 2 months. Statistical models (logistic regression, survival analysis, ROC curves, clustering) will be used.
This study complies with the Declaration of Helsinki, EU Regulation 536/2014, MR004 guidelines (CNIL), and French Public Health laws 2004-806, 2004-800, and 2016-41.
Study Type Observational
Observational Model: Cross-sectional
Time Perspective: Retrospective
Biospecimen Retention: Samples retained (Slides; No DNA)
Primary Outcome Measure Hepatic TREM-1 Expression
Type: Binary categorical variable (high vs. low)
Time Frame: At the day of liver biopsy
Method: Immunohistochemistry (Duan et al. score)
Secondary Outcome Measures Diagnostic Accuracy of TREM-1
Sensitivity, specificity, PPV, NPV for sAH diagnosis
Gold standard: multidisciplinary diagnosis
Time Frame: at the day of liver biopsy
Jaundice Resolution
Binary variable: resolved/persistent at Day 7
Time Frame: 7 days after corticosteroid start
Lille Score < 0.45
Prognostic response to corticosteroids
Time Frame: Day 7
Mortality at 2 Months
Time Frame: 60 days post-diagnosis
Analysis: Cox regression
Cluster Analysis of sAH Subgroups
Based on TREM-1 expression and clinico-biological profiles
Comparison to Established Prognostic Scores
MELD, AHHS, Glasgow, Maddrey, SALVE, Lille, Lille-MELD
TREM-1 expression in RNAseq3' in SAH patients
categorical variable (detected vs undetected) and quantitative variable (TREM expression as fragments per millions)
Comparison of TREM-1 expression in RNAseq3' in SAH patients to prognostic scores and outcomes
MELD, AHHS, Glasgow, Maddrey, SALVE, Lille, Lille-MELD Infection from day 3 to day 180 Mortality at M2, M3 and M6 Overall Mortality Response to steroids
Enrollment Estimated Enrollment: 300
Sampling Method: Non-probability sample
Eligibility Criteria
Inclusion Criteria (Cases):
Adults (≥18) with biopsy-proven severe alcohol-associated hepatitis (2013-2024)
Available liver biopsy slides at CHRU Nancy
Non-opposition documented
Inclusion Criteria (Controls):
Adults (≥18) with hepatic resection for colorectal metastases, cholangiocarcinoma, or HCC
Archived liver samples available
Non-opposition documented
Exclusion Criteria:
No histologic diagnosis of sAH
Depleted paraffin blocks unsuitable for staining
Study Dates Start Date: Upon ethics approval
Primary Completion Date: ~9 months after start
Study Completion Date: ~15 months after start
Locations CHRU Nancy, France Lead Pathology and Hepatology Units Collaborating Site: Hôpital Henri Mondor (AP-HP)
Sponsor and Contacts Sponsor: CHRU Nancy Scientific PI: Dr. Vincent Haghnejad Email: v.haghnejad@chru-nancy.fr Phone: +33 625150180
Regulatory Compliance
This study adheres to the following regulations and ethical standards:
Declaration of Helsinki
EU Regulation (EU) 536/2014
French Public Health Law: 2004-806, 2004-800, 2016-41
Bioethics Law and GDPR (EU 2016/679)
CNIL MR004 framework for retrospective, non-interventional data use
Statistical Methods
Primary Objective:
Logistic regression (univariate p<0.2 threshold, stepwise multivariate model) to compare TREM-1 expression between cases and controls.
Secondary Objectives:
ROC curve analysis to determine optimal antibody dilution (AUC, Youden index).
Diagnostic accuracy metrics (sensitivity, specificity, PPV, NPV).
Clustering (Multiple Correspondence Analysis + Ward's Hierarchical Clustering) for subgroup discovery.
Cox model for 2-month mortality.
Logistic regression for treatment response (Day 7 jaundice, Lille score <0.45).
Comparative model performance vs. MELD, Maddrey, etc.
Software: SAS 9.4 or R
Significance Level: 5% (two-sided)
- Conditions
- Severe Alcoholic Hepatitis
- Being tested
- TREM-1 expression (via immunohistochemistry) between SAH patients and controls
- Keywords
- TREM-1, sAH, biomarker, prognosis, alcoholic hepatitis, alcohol use disorder, AUD, cirrhosis
- Medical subject headings
- Hepatitis, Alcoholic, Alcoholism, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TREM-1 expression (via immunohistochemistry) between SAH patients and controlsDiagnostic 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,
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: TREM-1 expression (via immunohistochemistry) between SAH patients and controls |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Day 0 index liver biopsy
Secondary outcomes (1)
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.
Measured: Day 0 (index liver biopsy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2025
- Study start1 Oct 2025 (estimated)
- Primary completionOct 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Severe Alcoholic HepatitisStudies of the same condition, open and under way.
- More trials run by Central Hospital, Nancy, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Central Hospital, Nancy, France
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, HAGHNEJAD Vincent, Central Hospital, Nancy, France
- Investigators
- Vincent Haghnejad, MD, Principal investigator, CHRU de Nancy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07176741
- Sponsor's protocol ID
- 2023PI101
- Acronym
- Liver TREM-1
- Status last verified
- Sep 2025
- First submitted
- 15 Jun 2025
- Last updated
- 16 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25465376Ichou 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.
PubMed 26141143Francois 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.
PubMed 37350989Francois 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.
PubMed 37269870Francois 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.
PubMed 32468087Mathurin 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.
PubMed 8964410
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Measurement of Hepatocyte TREM-1 Expression Level to Evaluate Its Intrinsic Performance and Prognostic Value in Severe Symptomatic Alcohol-related Hepatitis
- ClinicalTrials.gov ID
- NCT07176741
- Acronym / sponsor ID
- Liver TREM-1 / 2023PI101
- Conditions
- Severe Alcoholic Hepatitis
- Keywords
- TREM-1, sAH, biomarker, prognosis, alcoholic hepatitis, alcohol use disorder, AUD, cirrhosis
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Central Hospital, Nancy, FranceUniversity, hospital or other
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 16 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Study Title
Official Title:
Liver TREM-1: Hepatic Expression of TREM-1 in Severe Alcoholic Hepatitis
Brief Summary (250 words max) Severe alcohol-associated hepatitis (sAH) is a life-threatening liver disease with a 3-month mortality rate of up to 30%. The only validated treatment-corticosteroids-fails in approximately 40% of patients, increases infection risk, and offers no survival benefit beyond 28 days. Therefore, there is an urgent need to identify prognostic biomarkers to guide therapy.
TREM-1 (Triggering Receptor Expressed on Myeloid cells 1) is a pro-inflammatory receptor expressed on hepatic immune and endothelial cells. Preclinical murine studies suggest it plays a pivotal role in alcohol-induced liver injury. This observational study aims to assess the diagnostic and prognostic value of hepatic TREM-1 expression in patients with severe alcohol-associated hepatitis using archived liver biopsy samples.
A total of 300 archived liver specimens (150 sAH cases, 150 controls with hepatic malignancies) will be analyzed via immunohistochemistry using a validated TREM-1 scoring system. Outcomes include TREM-1 expression levels, correlation with clinical parameters, mortality at 2 months, and response to corticosteroid therapy.
Detailed Description The study will determine whether hepatic TREM-1 expression can serve as a biomarker to stratify sAH patients into prognostic subgroups. TREM-1 expression will be measured via immunostaining and categorized as high vs. low using a score developed by Duan et al. Secondary analyses include diagnostic accuracy, treatment response (based on jaundice regression and Lille score at Day 7), and survival at 2 months. Statistical models (logistic regression, survival analysis, ROC curves, clustering) will be used.
This study complies with the Declaration of Helsinki, EU Regulation 536/2014, MR004 guidelines (CNIL), and French Public Health laws 2004-806, 2004-800, and 2016-41.
Study Type Observational
Observational Model: Cross-sectional
Time Perspective: Retrospective
Biospecimen Retention: Samples retained (Slides; No DNA)
Primary Outcome Measure Hepatic TREM-1 Expression
Type: Binary categorical variable (high vs. low)
Time Frame: At the day of liver biopsy
Method: Immunohistochemistry (Duan et al. score)
Secondary Outcome Measures Diagnostic Accuracy of TREM-1
Sensitivity, specificity, PPV, NPV for sAH diagnosis
Gold standard: multidisciplinary diagnosis
Time Frame: at the day of liver biopsy
Jaundice Resolution
Binary variable: resolved/persistent at Day 7
Time Frame: 7 days after corticosteroid start
Lille Score < 0.45
Prognostic response to corticosteroids
Time Frame: Day 7
Mortality at 2 Months
Time Frame: 60 days post-diagnosis
Analysis: Cox regression
Cluster Analysis of sAH Subgroups
Based on TREM-1 expression and clinico-biological profiles
Comparison to Established Prognostic Scores
MELD, AHHS, Glasgow, Maddrey, SALVE, Lille, Lille-MELD
TREM-1 expression in RNAseq3' in SAH patients
categorical variable (detected vs undetected) and quantitative variable (TREM expression as fragments per millions)
Comparison of TREM-1 expression in RNAseq3' in SAH patients to prognostic scores and outcomes
MELD, AHHS, Glasgow, Maddrey, SALVE, Lille, Lille-MELD Infection from day 3 to day 180 Mortality at M2, M3 and M6 Overall Mortality Response to steroids
Enrollment Estimated Enrollment: 300
Sampling Method: Non-probability sample
Eligibility Criteria
Inclusion Criteria (Cases):
Adults (≥18) with biopsy-proven severe alcohol-associated hepatitis (2013-2024)
Available liver biopsy slides at CHRU Nancy
Non-opposition documented
Inclusion Criteria (Controls):
Adults (≥18) with hepatic resection for colorectal metastases, cholangiocarcinoma, or HCC
Archived liver samples available
Non-opposition documented
Exclusion Criteria:
No histologic diagnosis of sAH
Depleted paraffin blocks unsuitable for staining
Study Dates Start Date: Upon ethics approval
Primary Completion Date: ~9 months after start
Study Completion Date: ~15 months after start
Locations CHRU Nancy, France Lead Pathology and Hepatology Units Collaborating Site: Hôpital Henri Mondor (AP-HP)
Sponsor and Contacts Sponsor: CHRU Nancy Scientific PI: Dr. Vincent Haghnejad Email: v.haghnejad@chru-nancy.fr Phone: +33 625150180
Regulatory Compliance
This study adheres to the following regulations and ethical standards:
Declaration of Helsinki
EU Regulation (EU) 536/2014
French Public Health Law: 2004-806, 2004-800, 2016-41
Bioethics Law and GDPR (EU 2016/679)
CNIL MR004 framework for retrospective, non-interventional data use
Statistical Methods
Primary Objective:
Logistic regression (univariate p<0.2 threshold, stepwise multivariate model) to compare TREM-1 expression between cases and controls.
Secondary Objectives:
ROC curve analysis to determine optimal antibody dilution (AUC, Youden index).
Diagnostic accuracy metrics (sensitivity, specificity, PPV, NPV).
Clustering (Multiple Correspondence Analysis + Ward's Hierarchical Clustering) for subgroup discovery.
Cox model for 2-month mortality.
Logistic regression for treatment response (Day 7 jaundice, Lille score <0.45).
Comparative model performance vs. MELD, Maddrey, etc.
Software: SAS 9.4 or R
Significance Level: 5% (two-sided)
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Biopsy-proven severe alcoholic hepatitis and control liver specimens | – | Diagnostic Test: TREM-1 expression (via immunohistochemistry) between SAH patients and controlsCases: Adults treated at CHRU de Nancy (2013-2023) for Severe Alcoholic Hepatitis, with archived liver biopsies. Controls: Adults with liver malignancies and archived biopsies. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (10 listed)
- 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.
- Individuals who received full information about the study and did not object to the use of their data within this research.
Key exclusion criteria (1 listed)
- None
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TREM-1 expression (via immunohistochemistry) between SAH patients and controlsthis 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, | Diagnostic test | Biopsy-proven severe alcoholic hepatitis and control liver specimens |
Primary outcome
Baseline Hepatocyte TREM-1 expression in SAH patients vs. controls on the day of biopsy
Time frame: Day 0 index liver 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).
1 secondary outcome
Baseline TREM-1 expression (via RNAseq3') in patients with severe alcohol-associated hepatitis (SAH)
Time frame: Day 0 (index liver biopsy)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2025.
- Background: PubMed 25465376Duan 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.
- Background: PubMed 26141143Ichou 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.
- Background: PubMed 37350989Francois 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.
- Background: PubMed 37269870Francois 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.
- Background: PubMed 32468087Francois 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.
- Background: PubMed 8964410Mathurin 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Vincent Haghnejad, MD principal investigator
CHRU de Nancy
Questions about this trial
What is this clinical trial studying?
An observational study of Severe Alcoholic Hepatitis, run by Central Hospital, Nancy, France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Vincent HAGHNEJAD, MD (+33383153354, v.haghnejad@chru-nancy.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline Hepatocyte TREM-1 expression in SAH patients vs. controls on the day of biopsy (time frame: Day 0 index liver biopsy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07176741, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2025.