1. Circulating PCSK9 levels are not associated with the severity of hepatic steatosis and NASH in a high-risk population
- Author
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Bertrand Cariou, Odile Blanchet, Matthieu Wargny, Sarra Smati, L. Arnaud, Matthieu Pichelin, Benjamin Bouillet, Luc Van Gaal, Sven Francque, Philippe Lefebvre, Jean-Michel Petit, Jérôme Boursier, Pierre-Henri Ducluzeau, Cédric Le May, Bart Staels, Adrien Lannes, Bruno Vergès, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Endocrinologie (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Bourgogne Franche-Comté [COMUE] (UBFC), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département d'hépatologie (CHU Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de Ressources Biologiques [CHU d'Angers] (CRB CHU d'Angers BB-0033-00038), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Gastroenterology and Hepatology (Antwerp University Hospital), Antwerp University Hospital [Edegem] (UZA), Department of Endocrinology, Diabetology and Metabolism (Antwerp University Hospital), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), LUNAM Université, F-49933 Angers, France, Plateforme PACeM (Plateforme d'Analyse Cellulaire et Moléculaire), SFR ICAT4208, F-49933 Angers, France., PACeM Angers, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Unité de recherche de l'institut du thorax (ITX-lab), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateforme d'Analyse Cellulaire et Moléculaire [SFR ICAT - UA] (PACEM), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA)-Université d'Angers (UA), ANR-16-RHUS-0007,CHOPIN,CHOPIN(2016), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)
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0301 basic medicine ,Male ,Biopsy ,Liver steatosis ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Gastroenterology ,Severity of Illness Index ,PCSK9 ,0302 clinical medicine ,Fibrosis ,Non-alcoholic Fatty Liver Disease ,LDL-cholesterol ,ComputingMilieux_MISCELLANEOUS ,education.field_of_study ,medicine.diagnostic_test ,Middle Aged ,Liver biopsy ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,Magnetic Resonance Imaging ,3. Good health ,Liver ,Female ,France ,Proprotein Convertase 9 ,Cardiology and Cardiovascular Medicine ,MRI ,Adult ,Risk ,medicine.medical_specialty ,Population ,Liver fibrosis ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Internal medicine ,medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Humans ,education ,Aged ,business.industry ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Hepatology ,medicine.disease ,Fatty Liver ,030104 developmental biology ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,Linear Models ,Human medicine ,Steatosis ,Steatohepatitis ,business - Abstract
Background and aims: Some studies suggested that proprotein convertase subtilisin kexin type 9 (PCSK9) is linked to liver steatosis severity and non-alcoholic steatohepatitis (NASH). We aimed to assess whether circulating PCSK9 levels are associated with either liver fat content (LFC) or histological markers of NASH in high-risk patients. Methods: We present results from three cross-sectional studies from two French Hospitals: Dijon and Numevox (departments of Endocrinology) and Angers (department of Hepatology). Only patients without lipid-lowering therapy were included. All 132 patients had type 2 diabetes in Dijon, compared to 55/224 in Numevox (25%) and 39/122 in Angers (32%). LFC was assessed on MRI (Dijon and Numevox), and NASH lesion on liver biopsy (Angers). Additionally, we included mRNA results from 138 overweight patients of a Belgian Hospital (Antwerp). Results: While circulating levels of PCSK9 were positively correlated with total cholesterol, LDL-C, triglycerides and non-HDL-C in all 3 cohorts, no significant association was found between PCSK9 and transaminases. Furthermore, no association was found between plasma PCSK9 levels and LFC in both Numevox (beta(adjusted) = 0.71 +/- 1.33, p = 0.60) and Dijon (beta(adjusted) = 1.03 +/- 0.90, p = 0.25). There was no correlation between circulating PCSK9 and histological liver lesions: steatosis severity (beta(adjusted) = -3.95 +/- 2.75, p = 0.15), NASH activity score (beta(adjusted) = -0.31 +/- 0.17, p = 0.082), lobular (beta = -0.067 +/- 0.055, p = 0.22) or portal inflammation (beta = -0.088 +/- 0.079, p = 0.27), ballooning (beta = -0.025 +/- 0.065, p = 0.70) and fibrosis (beta = -0.17 +/- 0.11, p = 0.12). Finally, hepatic PCSK9 mRNA levels were not correlated with NASH histological severity. Conclusions: Circulating PCSK9 concentrations are not associated with the severity of liver steatosis or histological markers of NASH. These data are reassuring regarding the clinical use of PCSK9 inhibitors in cardiovascular diseases.
- Published
- 2018
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