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

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

doi:10.3390/jcm11051223

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

J Clin Med. 2022 Feb 24;11(5):1223. doi: 10.3390/jcm11051223.

Authors

Eline H van den Berg¹, Jose L Flores-Guerrero², Eke G Gruppen², Erwin Garcia³, Margery A Connelly³, Vincent E de Meijer⁴, Stephan J L Bakker², Hans Blokzijl¹, Robin P F Dullaart⁵

Affiliations

¹ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
² Department of Nephrology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
³ Laboratory Corporation of America Holdings (Labcorp), Morrisville, NC 27560, USA.
⁴ Department of Hepatopancreatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
⁵ Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

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.

Keywords: HDL-cholesterol; LP-Z; NMR; cirrhosis; lipid profile; orthotopic liver transplantation.