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Circulating PCSK9 is associated with liver biomarkers and hepatic steatosis.

Lipids, Nutrition and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal, Canada. Laboratory of Biochemical Neuroendocrinology of the Montreal Clinical Research Institute, Montreal, Canada. Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom. Centre of Endocrinology and Metabolism, Department of Internal Medicine, Copenhagen University Hospitals, Herlev and Gentofte, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark. Centre for Public Health Research, KEMRI, Nairobi, Kenya. Lipids, Nutrition and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal, Canada; Department of Medicine, Division of Endocrinology, Université de Montreal, Montreal, Canada. Medical Research Council Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, United Kingdom; Department of Public Health, University of Copenhagen, Copenhagen, Denmark. Lipids, Nutrition and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Montreal, Canada; Department of Medicine, Divisions of Experimental Medicine and Medical Biochemistry, McGill University, Montreal, Canada. Electronic address: alexis.baass@ircm.qc.ca.

Clinical biochemistry. 2020;:20-25
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Abstract

BACKGROUND In parallel to the increasing prevalence of metabolic syndrome, the prevalence of hepatic steatosis has also increased dramatically worldwide. Hepatic steatosis is a major risk factor of hepatic cirrhosis, cardiovascular disease and type 2 diabetes. Circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) have been positively associated with the metabolic syndrome. However, the association between PCSK9 and the liver function is still controversial. OBJECTIVE The objective of this study is to investigate the association between circulating PCSK9 levels and the presence of hepatic steatosis, as well as with liver biomarkers in a cohort of healthy individuals. METHODS Total PCSK9 levels were measured by an in-house ELISA using a polyclonal antibody. Plasma albumin, alkaline phosphatase, ALT, AST, total bilirubin and GGT were measured in 698 individuals using the COBAS system. The presence of hepatic steatosis was assessed using ultrasound liver scans. RESULTS In a multiple regression model adjusted for age, sex, insulin resistance, body mass index and alcohol use, circulating PCSK9 level was positively associated with albumin (β = 0.102, P = 0.008), alkaline phosphatase (β = 0.201, P < 0.0001), ALT (β = 0.238, P < 0.0001), AST (β = 0.120, P = 0.003) and GGT (β = 0.103, P = 0.007) and negatively associated with total bilirubin (β = -0.150, P < 0.0001). Tertile of circulating PCSK9 was also associated with hepatic steatosis (OR 1.48, 95% CI 1.05-2.08, P = 0.02). CONCLUSION Our data suggest a strong association between PCSK9 and liver biomarkers as well as hepatic steatosis. Further studies are needed to explore the role of PCSK9 on hepatic function.