Profoundly Disturbed Lipoproteins in Cirrhotic Patients: Role of Lipoprotein-Z, a Hepatotoxic LDL-like Lipoprotein.

Eline H. van den Berg,Vincent E. de Meijer,Hans Blokzijl,Robin P. F. Dullaart,Margery A. Connelly,Eke G. Gruppen,Erwin Garcia,Jose L. Flores-Guerrero,Stephan J. L. Bakker

doi:10.3390/jcm11051223

Abstract

Detailed information regarding lipoprotein concentrations and subfractions in cirrhotic patients before and after orthotopic liver transplantation (OLT) is lacking. Lipoprotein-Z (LP-Z) is a recently characterised abnormal, hepatotoxic free cholesterol-rich low-density lipoprotein (LDL)-like lipoprotein. We determined the lipoprotein profiles, including LP-Z, in cirrhotic patients and OLT recipients and assessed the prognostic significance of LP-Z on the OLT waiting list. We performed analyses in cirrhotic transplant candidates and non-cirrhotic OLT recipients. A population-based cohort was used as reference. The setting was a University hospital. Lipoprotein particle concentrations and subfractions were measured by nuclear magnetic resonance spectroscopy. In the cirrhotic patients (N = 130), most measures of triglyceride-rich lipoproteins (TRL), LDL, and high-density lipoproteins (HDL) were much lower compared to the OLT recipients (N = 372) and controls (N = 6027) (p < 0.01). In the OLT recipients, many lipoprotein variables were modestly lower, but HDL-cholesterol, triglycerides, and TRL and HDL size were greater vs. the control population. LP-Z was measurable in 40 cirrhotic patients and 3 OLT recipients (30.8% vs. 0.8%, p < 0.001). The cirrhotic patients with measurable LP-Z levels had profoundly lower HDL-cholesterol and particle concentrations (p < 0.001), and worse Child Pugh Turcotte classifications and MELD scores. The presence of LP-Z (adjusted for age, sex, and MELD score) predicted worse survival in cirrhotic patients (HR per 1 LnSD increment: 1.11, 95%CI 1.03–1.19, p = 0.003). In conclusion, cirrhotic patients have considerably lower plasma concentrations of all major lipoprotein classes with changes in lipoprotein subfraction distribution. After OLT, these lipoprotein abnormalities are in part reversed. LP-Z is associated with cirrhosis. Its presence may translate in disturbed HDL metabolism and worse survival.

Highlights

This article is an open access articleThe liver plays a central role in lipoprotein metabolism [1–3]
In the pre-transplant cirrhotic patients, the lipid profile was profoundly different compared to the orthotopic liver transplantation (OLT) recipients with lower plasma total cholesterol, high-density lipoproteins (HDL)-C, and low-density lipoprotein (LDL)-C, non-HDL cholesterol, and lower triglycerides, apolipoprotein A-I (apoA-I), total triglyceride rich lipoprotein particles (TRLP), and total HDL particles (HDLP) levels (Table 1, all p < 0.001)
triglyceride-rich lipoproteins (TRL) size was smaller, whereas LDL and HDL size were significantly greater in the pre-transplant cirrhotic patients (p < 0.001)

Summary

Introduction

This article is an open access articleThe liver plays a central role in lipoprotein metabolism [1–3]. The liver produces very low-density lipoproteins (VLDL) and high-density lipoproteins (HDL), as well as enzymes which are critically involved in extrahepatic lipoprotein metabolism, such as lecithin cholesterol acyltransferase (LCAT), an enzyme that is involved in the metabolism of HDL by its ability to esterify free cholesterol to cholesteryl esters [4,5] and hepatic lipase (HL), which distributed under the terms and conditions of the Creative Commons. Is able to hydrolyze triglycerides in various lipoproteins [5]. Low plasma levels of total cholesterol, as well as triglycerides, are common [9]. Previous studies have described low levels of VLDL, low-density lipoprotein cholesterol (LDL-C), HDL cholesterol (HDL-C), and apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I), which are major apolipoproteins associated with VLDL, LDL, and HDL, respectively [3].

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