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Discovery of stage-specific biomarkers of liver cirrhosis

​By analyzing the blood lipidome of patients with cirrhosis, a European collaboration involving the CEA-Joliot has discovered specific biomarkers for the different stages of the disease. This is an important step towards achieving a personalized and more effective management of this illness.

Published on 7 January 2022

There are limits to the liver's ability to regenerate. The successive assaults it is subjected to during a lifetime – alcohol consumption, viral infection, etc. – lead to the progressive accumulation of scar tissue. This in turn results in cirrhosis, which can be compensated by the body for a while. But once "decompensated", cirrhosis evolves in 30 to 40% of cases into acute-on-chronic liver failure (ACLF), a severe condition characterized by systemic inflammation and the failure of one or more organs (kidneys, liver, circulatory system, respiratory system). It would thus be helpful to have a diagnostic tool that indicates the precise stage of the disease.

With this in mind, the Joliot researchers studied the progression of 223 blood lipid levels in 826 patients with decompensated cirrhosis and chronic liver failure (ACLF), as well as in healthy volunteers and patients with compensated cirrhosis. The measurements were performed by liquid chromatography-high resolution mass spectrometry (LC-HRMS).

Several general findings have come about from this systematic analysis of the lipidome:

  • There are few if any significant differences between healthy patients and those with compensated cirrhosis.
  • A large, significant and generalized reduction in blood lipids (except fatty acids) is observed in patients with decompensated cirrhosis.
  • This reduction is even more marked in patients with ACLF.

Specifically, sphingolipids stand out for their ability to unambiguously differentiate compensated and decompensated cirrhosis. They are known for their structural properties within cells and are also involved in the regulation of immunity and cell survival. Among them, sphingomyelins located in cell membranes are the most sensitive to the transition from compensated to decompensated cirrhosis.

 In the case of ACLF, a subgroup of 17 lipids was identified. Among them, the researchers were able to isolate the most specific biomarkers, namely lysophosphatidylcholines and cholesteryl esters. The latter are greatly reduced during the transition from decompensated cirrhosis to liver failure.

 These results make it possible to consider a new approach to characterize the pathophysiology and biochemical mechanisms of liver cirrhosis.

 This work was conducted within the framework of the European project MICROB-PREDICT.

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