Albumin Modifications as Early Biomarkers of Chronic Liver Diseases
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 756
- 试验地点
- 14
- 主要终点
- Ability of HSA PTM to predict the evolution of liver damage at 3 year in patients with an advanced chronic liver disease (ACLD) as recently defined in the BAVENO VII recommendations based on FibroScan.
研究概览
简要总结
Chronic liver diseases, affecting over 800 million people worldwide, lead to approximately 2 million annual deaths. The need for early, sensitive diagnostic strategies to prevent disease progression and reduce mortality is still unmet. The traditional serum markers lack sensitivity and specificity, leading to the integration of these biomarkers into panel tests with algorithms or imaging measures. Despite their widespread use, these tests have limitations at an individual level, including an inability to predict disease progression or response to treatment. To address these shortcomings, our project proposes utilizing albumin post-translational modifications (PTM) as a predictive biomarker for liver disease progression. The hypothesis is that albumin modifications occur in the early stages of hepatocellular damage and are indicative of future liver diseases. These modifications can be detected through serum albumin isoform determination, albumin isoforms profiles or the albumin's ligand-binding capacities. Innovatively, the study will use the Serum Enhanced Binding (SEB) test, which identifies reduced ligand-binding capacities, and discusses a second patent for determining a typical isoform profile based on the hepatic injury type.
Our preliminary results from animal models and a proof-of-concept studies with patients support this hypotheses. Our previous studies demonstrated also significant differences in albumin isoform profiles in response to different types of hepatic injury and high sensitivity and specificity in the SEB test among cirrhotic patients.
The primary objective of the MALAHBAR project is to evaluate the capacity of albumin PTM to predict liver disease progression over three years in chronic liver disease patients. Secondary objectives include assessing the predictive ability of different albumin isoforms and the SEB test for liver disease progression, evaluating diagnostic performances and confirming characteristic albumin isoform profiles related to specific hepatic injuries. The study could represent a significant advancement in liver disease diagnostics and management, offering new insights into the role of albumin in liver pathology.
详细描述
More than 800 million people suffer from chronic liver disease (CLD) with approximately 2 million deaths per year. The progression of CLD, could be asymptomatic until the appearance of fibrosis, cirrhosis and sometimes hepatocellular carcinoma. The prevention and early diagnosis of liver disease is therefore a major public health issue.
Due to their lack of sensitivity and specificity, direct serum markers are now combined in " panel tests ", sometimes gathered and used in algorithms (FibroMeter, FibroTest, FIBROSpect, Hepascore…) to help diagnose fibrosis or cirrhosis and to assess the stage of liver damage. Other biomarkers, in particular molecules involved in the fibrosis process, (protein-based biomarkers, microRNA or collagen-based biomarkers) have been the subject of numerous studies, but have not yet led to clinically exploitable biomarkers for the medium- or long-term monitoring of CLD. Non-invasive, sensitive and specific biomarkers for the early detection of liver dysfunction leading to advanced liver disease are therefore still awaited.
It has been shown that chemical and structural modifications of human serum albumin (HAS) leading to different isoforms could be used as biomarkers for advanced liver disease. Our work supports the hypothesis that the main changes in HSA occur in the early stages of cellular liver damage and could be predictive of future liver disease. These modifications can be revealed by the profile of isoforms in the patient's serum, or even more efficiently by the binding capacities of HAS for different ligands with specific binding sites. On this basis, a patent application has been filed for the SEB (Serum enhanced binding) test.
The study plans to recruit 756 patients in 6 university hospital centers (CHU of Limoges, Angers, Poitiers, Tours, Rennes, and Pointe à Pitre). The recruitment period is of 1.5 year.
Each patient will be followed during 3 years maximumThe study requires no supplementary visit as compared to the standard care. Study visits will take place during usual visits of the standard care as follows:.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
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
- •At least 18 years old
- •With a compensated fibrosis defined by an hepatic elasticity ≥10 kPa measured by FibroScan®
- •Having had blood test at the hospital as part of a consultation or an hospitalisation at the inclusion including usual parameters for the liver disease follow-up
- •Affiliated with or beneficiaries of a social security system
- •Not opposed to participate to the study after being informed
排除标准
- •Patients suffering from decompensated cirrhosis or with an history of decompensated cirrhosis
- •Patients who received an albumin infusion in the month before the inclusion visit
- •Patients suffering from stage 4 or 5 renal failure (GFR < 29 ml/min/1,73m²)
- •Patients suffering from cancer
- •Pregnant or breastfeeding women or women of childbearing age without effective contraception (based on declaration)
- •Patients suffering from impairment of mental faculties or a psychiatric disorder which could interfere with the understanding of the study
研究组 & 干预措施
experimental arm
干预措施: blood sampling (Procedure)
结局指标
主要结局
Ability of HSA PTM to predict the evolution of liver damage at 3 year in patients with an advanced chronic liver disease (ACLD) as recently defined in the BAVENO VII recommendations based on FibroScan.
时间窗: Years 3
The primary outcome is the positive predictive value (VPP) of post-translational HSA modifications related to the worsening of the liver damage at 3 years . This will be determined by an augmentation of more than 20% as compared to the initial state, documented by FibroScan® or a liver related event as defined in BAVENO VII.
次要结局
- ability of post-translational HSA modifications to predict the evolution of liver damage at 3 years based on liver-related events or on the worsening of the disease stage evaluated by the de Child Pugh or MELD score.(Year 3)
- diagnostic performances of the SEB test and of the different isoforms of HSA at each stage of the liver disease.(year 3)
- confirm that the isoforms of HAS present in the characteristic patterns (type of isoform and intensity) of the nature of the liver damage.(Years 3)
- ability of SEB test to predict the evolution of liver damage at 3 years (and at 1 and 2 years provided data are available in the medical file).(Year 3)
- ability of the different isoforms of HSA to predict the evolution of liver damage at 1 and 2 years provided that data are available in the medical file.(year 2)