Cholesterol esterification in plasma as a biomarker for liver function and prediction of mortality

Abstract

BackgroundAdvanced stages of liver cirrhosis lead to a dramatically increased mortality. For valid identification of these patients suitable biomarkers are essential. The most important biomarkers for liver function are bilirubin and prothrombin time expressed as International Normalized Ratio (INR). However, the influence of several anticoagulants on the prothrombin time limits its diagnostic value.Aim of this study was the evaluation of cholesterol esterification (CE) fraction (esterified cholesterol vs. total cholesterol) as an alternative biomarker for liver synthesis and mortality prediction. Under physiological conditions the CE fraction in blood is closely regulated by lecithin-cholesterol acyltransferase (LCAT) which is produced in the liver.MethodsOne hundred forty-two patients with liver disease clinically considered for orthotopic liver transplant for different indications were enrolled in the study. One patient was excluded because of the intake of a direct oral factor Xa inhibitor which has a strong impact on prothrombin time.ResultsResults of CE fraction were in good agreement with INR (R2 = 0.73; p < 0.001). In patients who died or survived within three months mean CE fraction was 56% vs. 74% (p < 0.001) and mean INR was 2.0 vs. 1.3 (p < 0.001), respectively. The predictive value of CE fraction for three-month mortality risk was higher compared to INR (p = 0.04). Results for one-year mortality were comparable.ConclusionsThe cholesterol esterification fraction is a valid biomarker for liver synthesis and allows reliable prediction of mortality. In contrast to INR, it is independent of anticoagulation and other analytical limitations of coagulation tests.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-017-0614-9) contains supplementary material, which is available to authorized users.

Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis

“…We confirmed prior observations that %CE (and, hence, LCAT activity) decreases as liver disease progresses, 14 highlighted by the stark dichotomy of higher MELD scores and proportion of CP-C subjects in the subgroup with the lower %CE (tertile 3) compared to the subgroup with the highest %CE (tertile 1). As a proof of concept that indeed abnormal cholesterol metabolism is associated with the development of RAI, the relationship between %CE and development of RAI was fairly linear, such that each integer loss of %CE predicted an approximately 2% increase in the probability of RAI.…”

“…As %CE has been proposed as a novel biomarker of hepatic function, we stratified subjects into tertiles by %CE in accordance with prior literature (Table S1). 14 (Continues) significantly alter our findings. As seen in Figure 1, HDL levels were correlated with %CE (r = 0.70, R 2 = 0.49; P <.01).…”

“…13 LCAT activity is known to decrease in patients with cirrhosis, with literature suggesting it may serve as a surrogate marker of hepatic synthetic function. 14,15 However, LCAT activity and its relationship to RAI have not been defined.…”

“…This process is dependent on the presence of lecithin‐cholesterol acyltransferase (LCAT), an hepatically synthesized enzyme that binds to the apolipoprotein A1 component of HDL and facilitates esterification of free cholesterol 13 . LCAT activity is known to decrease in patients with cirrhosis, with literature suggesting it may serve as a surrogate marker of hepatic synthetic function 14,15 . However, LCAT activity and its relationship to RAI have not been defined.…”

Lipidomic signatures of post-hepatectomy liver failure using porcine hepatectomy models

“…Lipids are synthesized in the liver and exported to and from the rest of the body by lipoproteins (12). Lipid metabolism can be significantly altered during liver disease (13) or after liver resection (14)(15)(16)(17)(18)(19), suggesting their potential to be used as biomarkers in the setting of PHLF. However, lipid profiles during PHLF have not been thoroughly examined.…”