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Updated: Nov 4, 2025

The Murine Choline-Deficient, Ethionine-Supplemented CDE Diet Model of Chronic Liver Injury
Published on: October 21, 2017
Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis
Brian J Wentworth1, Rebecca M Haug2, Patrick G Northup1
1Division of Gastroenterology and Hepatology, University of Virginia Health System, Charlottesville, VA, USA.
Background And Aims:
Relative adrenal insufficiency (RAI) in patients with cirrhosis is associated with increased mortality. Although the pathogenesis of RAI remains unclear, disordered cholesterol metabolism may contribute.
Methods:
We performed a prospective cohort study of 96 non-critically ill subjects with decompensated cirrhosis at a tertiary care centre. Subjects were administered 250 µcg cosyntropin, with RAI defined as an increase in total cortisol <9 µg/dL. High-density lipoprotein (HDL) levels and serum cholesterol esterification percentage (%CE), a validated surrogate marker of lecithin-cholesterol acyltransferase (LCAT) activity, were measured to assess the relationship between disordered cholesterol metabolism and the presence of RAI. Subjects were followed until death, liver transplantation or a maximum of 6 months.
Results:
Subjects with RAI had decreased levels of HDL (18 vs 29 mg/dL, P < .01) and %CE (64% vs 66%, P = .03). Correlation was seen between HDL and %CE (r = 0.7, R2 = 0.49; P < .01) and each integer decrease in %CE predicted an approximately 2% increase in the probability of RAI. Transplant-free survival was reduced in subjects with RAI at both 6 months (43% vs 71%, P = .01) and 90 days (54% vs 81%, P < .01).
Conclusions:
Disruption in cholesterol metabolism contributes to the development of RAI in cirrhosis, as decreased LCAT activity leads to reduced HDL trafficking to the adrenal gland.
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