GDF15 is associated with hepatocellular senescence and correlates with mortality in patients with alcohol-associated hepatitis
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View abstract on PubMed
Summary
This summary is machine-generated.Hepatocellular senescence and elevated GDF15 levels are hallmarks of alcohol-associated hepatitis (AH), correlating with disease severity and poor outcomes. These findings highlight senescence as a potential driver and biomarker for AH.
Area Of Science
- Hepatology
- Cellular Biology
- Immunology
Background
- Cellular senescence, characterized by growth arrest and a proinflammatory secretory phenotype (SASP), is implicated in chronic liver diseases.
- The role of hepatocellular senescence in alcohol-associated liver disease (ALD) progression and alcohol-associated hepatitis (AH) is not well understood.
Purpose Of The Study
- To investigate the presence and significance of hepatocellular senescence in ALD, particularly AH.
- To identify potential biomarkers for AH progression and patient outcomes.
Main Methods
- Transcriptomic analysis of liver tissue from patients at various ALD stages (fibrosis, cirrhosis, AH).
- Evaluation of senescence markers (e.g., p21, CDKN1A, CDKN2A, CDKN2B, IL6, SERPINE1) and SASP factors, including GDF15.
- Measurement of plasma GDF15 levels in AH patients, cirrhotic patients, heavy drinkers, and healthy controls.
- Validation in independent cohorts.
Main Results
- Increased expression of senescence-associated genes and SASP signatures in cirrhosis and AH.
- Senescence markers correlated positively with AH clinical severity.
- Hepatocellular GDF15 expression was elevated in AH and associated with senescence markers.
- Plasma GDF15 levels were significantly increased in AH patients and correlated with severity.
- Plasma GDF15 predicted corticosteroid response and 90-day mortality in AH patients.
Conclusions
- AH is characterized by hepatocellular senescence and elevated circulating SASP factors, notably GDF15.
- Elevated GDF15 levels correlate with poor patient outcomes in AH.
- Senescence may play a role in AH pathogenesis and GDF15 could serve as a potential biomarker for AH.
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