Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis.

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.

Thrombocytopenia in Chronic Liver Disease and the Role of Thrombopoietin Agonists.

Thrombocytopenia is a common complication of chronic liver disease and creates clinical challenges for patients who need invasive procedures. Options available to increase platelet counts were previously limited to risk-laden therapies such as platelet transfusions, splenic artery embolization, and transjugular intrahepatic portosystemic shunts. Thrombopoietin (TPO) agonists can augment platelet production through TPO receptor agonism. Three oral TPO agents are currently available to increase platelet counts, and in 2018, 2 of these agents (avatrombopag and lusutrombopag) were approved by the US Food and Drug Administration for the purpose of increasing platelet counts in patients with chronic liver disease prior to an invasive procedure. This article summarizes the pathophysiology of thrombocytopenia in chronic liver disease, the clinical challenge that thrombocytopenia poses, and the trials that led to the approval of the TPO agonists. Also discussed are the clinical studies that have been the basis for expert opinions and target platelet levels for cirrhotic patients undergoing procedures. A specific platelet count has not demonstrated a decreased bleeding rate in the periprocedural period in randomized, controlled trials, and using TPO agonists is not devoid of risk. However, the newly approved agents have shown no increase in the rate of portal vein thrombosis in this population and have shown promising results for increasing platelet counts.