Albumin Modifications as Early Biomarkers of Chronic Liver Diseases — MALAHBAR  

Chronic Liver Disease Clinical Trial

Official title: Albumin Modifications as Early Biomarkers of Chronic Liver Diseases

Status Not yet recruiting

Clinical Trial Summary

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.

Clinical Trial Description

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, we have filed a patent application 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:.

• Inclusion visit : study information by the investigator and if the patient is not opposed to participate to the study, either blood sampling (a supplementary tube can be add to a routine blood sampling realised for standard cares) or re-use of a residual blood sample after routine tests have been done, and data collection from the medical file.

• Follow-up visits: visits at 1, 2 and 3 years depending to the diagnostic of the investigator. During these visits: collection of a blood sampling the same conditions described for the inclusion visit and data collection from the medical file.

The samples will be sent to the central laboratory in the CHU of Limoges (Pharmacology, Toxicology and Pharmacovigilance) where HSA isoforms will be analysed by LC-QTOF and SEB tests realised.

The main goal is to validate HAS modifications as biomarker able to predict the evolution of liver damage and thus prevent worsening of the liver disease and finally improve the quality of care. ;

Related Conditions & MeSH terms

• Chronic Liver Disease
• Liver Diseases

• NCT number: NCT06318949
• Study type: Interventional
• Source: University Hospital, Limoges
• Contact: Souleiman EL BALKHI, MD
• Phone: 0555058035
• Email: Souleiman.ElBalkhi@chu-limoges.fr
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Completion date: December 1, 2029