Liver disease alters high-density lipoprotein composition, metabolism and function

Area of Science:

• Cardiovascular Biology
• Hepatology
• Lipid Metabolism

Background:

• High-density lipoproteins (HDL) are crucial for inhibiting inflammation.
• HDL dysfunction may contribute to mortality in liver disease patients.
• The impact of cirrhosis on HDL metabolism and function is not well understood.

Purpose of the Study:

• To assess HDL quantity and quality in patients with compensated and acutely decompensated cirrhosis.
• To investigate the relationship between HDL alterations and clinical outcomes in liver disease.

Main Methods:

• Analyzed apolipoprotein (apo) B-depleted sera from cirrhotic patients and healthy controls.
• Assessed HDL-cholesterol levels, enzyme activities, and HDL subclass distribution (HDL2).
• Performed proteomic analysis of isolated HDL and evaluated functional metrics like cholesterol efflux capacity.

Main Results:

• Cirrhotic patients exhibited reduced HDL-cholesterol and suppressed HDL-associated enzyme activities.
• HDL in cirrhotic sera shifted towards the larger HDL2 subclass.
• Altered HDL protein composition (apoA-I, apoC-III, apoE, paraoxonase 1, SAA) correlated with impaired functions, including cholesterol efflux and anti-inflammatory capacity.
• Cholesterol efflux capacity was strongly associated with liver disease mortality.

Conclusions:

• Cirrhosis significantly alters HDL quantity, composition, and function.
• Impaired HDL cholesterol efflux capacity is a key metric associated with mortality in liver disease.
• These findings may aid in monitoring cirrhotic patients at high risk.