Circulating high density lipoprotein distinguishes alcoholic hepatitis from heavy drinkers and predicts 90-day outcome: lipoproteins in alcoholic hepatitis

Abstract

Background: Alcohol-associated liver disease (ALD) and alcoholic hepatitis (AH) significantly impact the liver, an organ central to the lipid and lipoprotein metabolism.

Objective: To define changes in the lipid and lipoprotein profiles in subjects with alcoholic hepatitis (AH) versus heavy drinkers with normal liver function and to determine the association of the AH-mediated lipoprotein phenotype with AH severity and outcomes.

Methods: AH cases (n=196) and a heavy drinker control group (n=169) were identified in a multicenter, prospective cohort. The relationships between lipid panels and lipoprotein profiles among AH and heavy drinkers were interrogated using three common measurements: the conventional lipid panel, extended lipid panel by NMR, and NMR-based direct lipoprotein profiling. Predictive values for AH severity and mortality were determined using Harrell's C-Index.

Results: Lipid and lipoprotein profiles were significantly different in AH compared to heavy drinkers. Among them, high density lipoprotein (HDL) particle concentration exhibited the most significant reduction in AH compared to heavy drinkers (5.3 ± 3.4 vs 22.3 ± 5.4 μmol/L, p < 0.001). Within AH patients, HDL particle concentration was inversely associated with Maddrey's Discriminant Function (DF) (p < 0.001), and independently associated with mortality at both 90 and 365 days even after adjustment for DF (p = 0.02, p = 0.05 respectively). HDL particle concentration less than 3.5 μmol/L and total cholesterol ≤ 96 mg/dL identified AH patients with higher 90-day mortality.

Conclusion: Lipid and lipoprotein profiles are profoundly altered in AH and can help in prognosticating disease severity and mortality.

Trial registration: ClinicalTrials.gov NCT02172898.

Keywords: Alcoholic hepatitis (AH); Nuclear magnetic resonance spectroscopy (NMR); high density lipoprotein (HDL); lipoproteins; total cholesterol (TC).

Conflict of interest statement

Conflict of interest statement

MAC is an employee of LabCorp that developed the NMR method to measure LP-Z concentration. The authors declare no additional competing interests pertinent to this study.

Copyright © 2021. Published by Elsevier Inc.

Figures

Figure 1. Comparisons of HDL levels between heavy drinkers and AH patients.

Box and Whisker plots of total HDL (A) and its subclasses: large (B), medium (C), and small (D) particle concentrations in heavy drinkers and AH patients. P-values calculated by Student’s t-test.

Figure 2. Kaplan-Meyer analysis of HDL and TC levels predicting 90-day survival.

Kaplan-Meyer survival curves at 90 days are compared between AH patients with HDL particle molar concentration ≤ 3.5 μmol/L vs. HDL > 3.5 μmol/L (A), and total cholesterol (TC) ≤ 96 mg/dL vs. TC > 96 mg/dL (B). P-values calculated by log-rank test. The number-at-risk tables are shown under each plot.

Figure 3. Diagrams of lipid and lipoprotein changes in ALD and AH

Conceptual diagrams of serum lipids (A) and lipoproteins (B) across alcohol-related fatty liver to mild, moderate, and severe alcoholic hepatitis.