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. 2021 Aug;41(8):1913-1921.
doi: 10.1111/liv.14970. Epub 2021 Jun 8.

Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis

Brian J Wentworth  1 , Rebecca M Haug  2 , Patrick G Northup  1 , Stephen H Caldwell  1 , Zachary H Henry  1
Affiliations

Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis

Brian J Wentworth et al. Liver Int. 2021 Aug.

Abstract

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.

Keywords: cholesterol metabolism; decompensated cirrhosis; hepatoadrenal syndrome; lecithin-cholesterol acyltransferase; relative adrenal insufficiency.

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References

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