Patients with cirrhosis can experience sudden clinical deterioration, progressing from acute decompensation to acute-on-chronic liver failure. However, the biological processes that precede this transition are not fully understood.

In this study from the DECISION project, we used single-cell technologies to investigate immune cell function at an unprecedented level of detail.

By analyzing thousands of individual immune cells from patients with advanced liver disease, we identified a consistent pattern: monocytes show a marked loss of energy production before organ failure develops. This dysfunction is linked to impaired mitochondrial activity, leaving the cells present but functionally compromised.

Importantly, this monocyte-specific energy failure was observed across large patient cohorts and was associated with infections, disease progression, and reduced survival.

These findings indicate that immune dysfunction in cirrhosis develops gradually at the level of cellular metabolism. Understanding how immune cells lose their energy may help explain why patients become vulnerable to complications and may inform future therapeutic strategies aimed at preserving immune function.

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📖 We’ll link the paper once it’s published.

Patients with cirrhosis can experience sudden and severe deterioration, progressing from acute decompensation to acute-on-chronic liver failure. However, the biological mechanisms underlying this transition are not fully understood.

In a new study from the DECISION project, we investigated whether epigenetic regulation, specifically DNA methylation, could help explain differences in disease progression.

Epigenetics refers to molecular mechanisms that regulate gene activity without altering the DNA sequence itself. One such mechanism, DNA methylation, involves the addition of small chemical tags that can activate or silence genes.

By analyzing DNA methylation patterns in patients with acute decompensation of cirrhosis, we observed that patients with worse outcomes exhibited higher global DNA methylation, suggesting a broad shift in gene regulation. In addition, specific epigenetic changes were identified near genes involved in key biological processes, including inflammation, immune response, metabolism, and liver function.

These findings highlight the role of epigenetic regulation in the progression of advanced liver disease and suggest that integrating molecular data may improve disease monitoring and risk stratification in the future.

🎥 Watch the video!
📖 We’ll link the paper once it’s published.