HDL-related biomarkers are robust predictors of survival in patients with chronic liver failure.

Acute-On-Chronic Liver Failure / blood Apolipoprotein A-I / blood Biomarkers Cholesterol, HDL / blood Cross-Sectional Studies Disease Progression Europe / epidemiology Female Humans Lipoproteins, HDL2 / blood Lipoproteins, HDL3 / blood Liver Cirrhosis / blood Male Middle Aged Organ Dysfunction Scores Predictive Value of Tests Prognosis Severity of Illness Index

ACLF HDL Inflammation MELD score apoA-I

Journal

Journal of hepatology

ISSN: 1600-0641

Titre abrégé: J Hepatol

Pays: Netherlands

ID NLM: 8503886

Informations de publication

Date de publication:
07 2020

Historique:

received: 16 08 2019

revised: 21 01 2020

accepted: 31 01 2020

pubmed: 18 2 2020

medline: 6 11 2021

entrez: 17 2 2020

Statut: ppublish

Résumé

High-density lipoprotein cholesterol (HDL-C) levels are reduced in patients with chronic liver disease and inversely correlate with disease severity. During acute conditions such as sepsis, HDL-C levels decrease rapidly and HDL particles undergo profound changes in their composition and function. We aimed to determine whether indices of HDL quantity and quality associate with progression and survival in patients with advanced liver disease. HDL-related biomarkers were studied in 508 patients with compensated or decompensated cirrhosis (including acute-on-chronic liver failure [ACLF]) and 40 age- and gender-matched controls. Specifically, we studied levels of HDL-C, its subclasses HDL2-C and HDL3-C, and apolipoprotein A1 (apoA-I), as well as HDL cholesterol efflux capacity as a metric of HDL functionality. Baseline levels of HDL-C and apoA-I were significantly lower in patients with stable cirrhosis compared to controls and were further decreased in patients with acute decompensation (AD) and ACLF. In stable cirrhosis (n = 228), both HDL-C and apoA-I predicted the development of liver-related complications independently of model for end-stage liver disease (MELD) score. In patients with AD, with or without ACLF (n = 280), both HDL-C and apoA-I were MELD-independent predictors of 90-day mortality. On ROC analysis, both HDL-C and apoA-I had high diagnostic accuracy for 90-day mortality in patients with AD (AUROCs of 0.79 and 0.80, respectively, similar to that of MELD 0.81). On Kaplan-Meier analysis, HDL-C <17 mg/dl and apoA-I <50 mg/dl indicated poor short-term survival. The prognostic accuracy of HDL-C was validated in a large external validation cohort of 985 patients with portal hypertension due to advanced chronic liver disease (AUROCs HDL-C: 0.81 vs. MELD: 0.77). HDL-related biomarkers are robust predictors of disease progression and survival in chronic liver failure. People who suffer from cirrhosis (scarring of the liver) have low levels of cholesterol carried by high-density lipoproteins (HDL-C). These alterations are connected to inflammation, which is a problem in severe liver disease. Herein, we show that reduced levels of HDL-C and apolipoprotein A-I (apoA-I, the main protein carried by HDL) are closely linked to the severity of liver failure, its complications and survival. Both HDL-C and apoA-I can be easily measured in clinical laboratories and are as good as currently used prognostic scores calculated from several laboratory values by complex formulas.

Sections du résumé

BACKGROUND & AIMS

METHODS

HDL-related biomarkers were studied in 508 patients with compensated or decompensated cirrhosis (including acute-on-chronic liver failure [ACLF]) and 40 age- and gender-matched controls. Specifically, we studied levels of HDL-C, its subclasses HDL2-C and HDL3-C, and apolipoprotein A1 (apoA-I), as well as HDL cholesterol efflux capacity as a metric of HDL functionality.

RESULTS

Baseline levels of HDL-C and apoA-I were significantly lower in patients with stable cirrhosis compared to controls and were further decreased in patients with acute decompensation (AD) and ACLF. In stable cirrhosis (n = 228), both HDL-C and apoA-I predicted the development of liver-related complications independently of model for end-stage liver disease (MELD) score. In patients with AD, with or without ACLF (n = 280), both HDL-C and apoA-I were MELD-independent predictors of 90-day mortality. On ROC analysis, both HDL-C and apoA-I had high diagnostic accuracy for 90-day mortality in patients with AD (AUROCs of 0.79 and 0.80, respectively, similar to that of MELD 0.81). On Kaplan-Meier analysis, HDL-C <17 mg/dl and apoA-I <50 mg/dl indicated poor short-term survival. The prognostic accuracy of HDL-C was validated in a large external validation cohort of 985 patients with portal hypertension due to advanced chronic liver disease (AUROCs HDL-C: 0.81 vs. MELD: 0.77).

CONCLUSION

HDL-related biomarkers are robust predictors of disease progression and survival in chronic liver failure.

LAY SUMMARY

People who suffer from cirrhosis (scarring of the liver) have low levels of cholesterol carried by high-density lipoproteins (HDL-C). These alterations are connected to inflammation, which is a problem in severe liver disease. Herein, we show that reduced levels of HDL-C and apolipoprotein A-I (apoA-I, the main protein carried by HDL) are closely linked to the severity of liver failure, its complications and survival. Both HDL-C and apoA-I can be easily measured in clinical laboratories and are as good as currently used prognostic scores calculated from several laboratory values by complex formulas.

Identifiants

DOI: 10.1016/j.jhep.2020.01.026 PMID: 32061870

pubmed: 32061870

pii: S0168-8278(20)30073-8

doi: 10.1016/j.jhep.2020.01.026

pii:

doi:

Substances chimiques

Apolipoprotein A-I 0

Biomarkers 0

Cholesterol, HDL 0

Lipoproteins, HDL2 0

Lipoproteins, HDL3 0

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

113-120

Commentaires et corrections

Type : CommentIn

Informations de copyright

Déclaration de conflit d'intérêts

Conflicts of interest Alexander Gerbes received personal fees from CSL Behring, GRIFOLS, and Falk. All other authors declare that they have no conflicts of interest related to the study. Please refer to the accompanying ICMJE disclosure forms for further details.