医学
内科学
脂肪变性
脂肪性肝炎
PCSK9
血脂异常
脂肪肝
胃肠病学
肝病学
人口
肝活检
2型糖尿病
内分泌学
胆固醇
糖尿病
活检
肥胖
脂蛋白
低密度脂蛋白受体
疾病
环境卫生
作者
Matthieu Wargny,Pierre-Henri Ducluzeau,Jean-Michel Petit,Cédric Le May,Sarra Smati,Lucie Arnaud,Matthieu Pichelin,Benjamin Bouillet,Adrien Lannes,Odile Blanchet,Philippe Lefebvre,Sven Francque,Luc Van Gaal,Bart Staels,Bruno Vergès,Jérôme Boursier,Bertrand Cariou
标识
DOI:10.1016/j.atherosclerosis.2018.09.008
摘要
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.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).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 (βadjusted = 0.71 ± 1.33, p = 0.60) and Dijon (βadjusted = -1.03 ± 0.90, p = 0.25). There was no correlation between circulating PCSK9 and histological liver lesions: steatosis severity (βadjusted = -3.95 ± 2.75, p = 0.15), NASH activity score (βadjusted = -0.31 ± 0.17, p = 0.082), lobular (β = -0.067 ± 0.055, p = 0.22) or portal inflammation (β = -0.088 ± 0.079, p = 0.27), ballooning (β = -0.025 ± 0.065, p = 0.70) and fibrosis (β = -0.17 ± 0.11, p = 0.12). Finally, hepatic PCSK9 mRNA levels were not correlated with NASH histological severity.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.
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