Measurement of Hepatocyte TREM-1 Expression Level to Evaluate Its Intrinsic Performance and Prognostic Value in Severe Symptomatic Alcohol-related Hepatitis
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 300
- 主要终点
- Baseline Hepatocyte TREM-1 expression in SAH patients vs. controls on the day of biopsy
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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,
- •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.
- •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,
- •Archived liver biopsy slides available at CHRU de Nancy.
- •Adult patients at the time of diagnosis.
排除标准
- 未提供
结局指标
主要结局
Baseline Hepatocyte TREM-1 expression in SAH patients vs. controls on the day of biopsy
时间窗: 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).
次要结局
- Baseline TREM-1 expression (via RNAseq3') in patients with severe alcohol-associated hepatitis (SAH)(Day 0 (index liver biopsy))
研究者
HAGHNEJAD Vincent
Dr
Central Hospital, Nancy, France