Non-alcoholic fatty liver disease (NAFLD) is becoming the main cause of liver disease in Western countries, especially in morbidly obese patients (MOPs). The proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently studied because of its possible involvement in the pathogenesis of NAFLD, but its role, at least in MOPs, is still controversial. The aim of this study was to clarify the correlation between the circulating levels of the PCSK9 protein (cPCSK9) and its hepatic expression with the severity of liver damage in a population of MOPs with NAFLD undergoing bariatric surgery. PCSK9 mRNA was positively correlated with FASN, PPARγ and PPARα mRNAs, while no significant differences were found in PCSK9 mRNA expression in relation to the severity of liver steatosis, lobular inflammation and hepatocellular ballooning. In addition, hepatic PCSK9 protein expression levels were not related to histological parameters of lobular inflammation and hepatocyte ballooning, decreased significantly only in relation to the severity of hepatic steatosis, and were inversely correlated with ALT and AST serum levels. cPCSK9 levels in the whole population were associated with the severity of hepatic steatosis and were positively correlated to total cholesterol levels. In multivariate analysis, cPCSK9 levels were associated with age, total cholesterol and HbA1c. In conclusion, in MOPs our findings support a role for PCSK9 in liver fat accumulation, but not in liver damage progression, and confirm its role in the increase of blood cholesterol, which ultimately may contribute to increased cardiovascular risk in this population.

在西方国家，非酒精性脂肪肝疾病（NAFLD）成为肝病的主要原因，尤其是在病态肥胖患者（MOPs）中。前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）由于其可能参与了NAFLD的发病机理，因此最近已进行了研究，但至少在MOP中的作用仍存在争议。这项研究的目的是弄清在进行减肥手术的患有NAFLD的MOP人群中，PCSK9蛋白（cPCSK9）的循环水平与其肝脏表达与肝损害严重程度之间的相关性。PCSK9 mRNA与FASN，PPARγ和PPARαmRNA呈正相关，而PCSK9 mRNA表达与肝脂肪变性，小叶炎症和肝细胞膨胀的严重程度之间无显着差异。此外，肝PCSK9蛋白表达水平与小叶炎症和肝细胞膨胀的组织学参数无关，仅与肝脂肪变性的严重程度显着降低，而与ALT和AST血清水平呈负相关。整个人群中的cPCSK9水平与肝脂肪变性的严重程度相关，并且与总胆固醇水平呈正相关。在多变量分析中，cPCSK9水平与年龄，总胆固醇和HbA1c相关。总之，在MOP中，我们的发现支持PCSK9在肝脂肪蓄积中的作用，但在肝损害的进展中不起作用，并证实了PCSK9在血胆固醇增加中的作用，这最终可能导致该人群心血管风险增加。