Fasolato Silvano, Pigozzo Sabrina, Pontisso Patrizia, Angeli Paolo, Ruscica Massimiliano, Savarino Edoardo, De Martin Sara, Lupo Maria Giovanna, Ferri Nicola
Department of Medicine, University of Padova, 35128 Padua, Italy.
Department of Pharmacological and Biomolecular Sciences, University of Milan, 20122 Milan, Italy.
J Clin Med. 2020 Sep 28;9(10):3134. doi: 10.3390/jcm9103134.
Since emerging evidence suggests a protective role of proprotein convertase subtilisin/kexin type 9 (PCSK9) on hepatitis C virus (HCV) infection, the aim of the present study was to evaluate the correlation between PCSK9 and HCV infection in hepatocellular carcinoma (HCC) patients. In this retrospective study, PCSK9 levels were evaluated by ELISA, in plasma samples from control ( = 24) and 178 patients diagnosed for HCC, cirrhosis, or chronic hepatitis, either positive or negative for HCV. HCV positive patients (HCV+) presented with higher PCSK9 levels compared to HCV negative individuals (HCV-), 325.2 ± 117.7 ng/mL and 256.7 ± 139.5 ng/mL, respectively. This difference was maintained in the presence of HCC, although this disease significantly reduced PCSK9 levels. By univariate analysis, a positive correlation between PCSK9 and HCV viral titer was found, being G2 genotype the most-potent inducer of PCSK9 among other genotypes. This induction was not associated with changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). A negative correlation was also found between PCSK9 levels and liver impairment, assessed by Model for End-Stage Liver Disease (MELD). Finally, a multivariate correlation analysis corrected for age, TC, LDL-C, and sex, demonstrated, in the whole cohort, a positive association between PCSK9 and HCV and a negative with HCC. taken together, our study reveals that HCV raised PCSK9 in both the presence and absence of HCC.
由于新出现的证据表明前蛋白转化酶枯草溶菌素/克新蛋白酶9型（PCSK9）对丙型肝炎病毒（HCV）感染具有保护作用，本研究旨在评估肝细胞癌（HCC）患者中PCSK9与HCV感染之间的相关性。在这项回顾性研究中，通过酶联免疫吸附测定法（ELISA）评估了对照组（n = 24）以及178例被诊断为HCC、肝硬化或慢性肝炎且HCV呈阳性或阴性的患者血浆样本中的PCSK9水平。与HCV阴性个体（HCV-）相比，HCV阳性患者（HCV+）的PCSK9水平更高，分别为325.2±117.7 ng/mL和256.7±139.5 ng/mL。尽管HCC会显著降低PCSK9水平，但在HCC存在的情况下这种差异仍然存在。通过单因素分析，发现PCSK9与HCV病毒滴度呈正相关，在其他基因型中，G2基因型是PCSK9的最强诱导剂。这种诱导与总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）和甘油三酯（TG）的变化无关。通过终末期肝病模型（MELD）评估，还发现PCSK9水平与肝功能损害呈负相关。最后，在对年龄、TC、LDL-C和性别进行校正的多因素相关性分析中，在整个队列中显示，PCSK9与HCV呈正相关，与HCC呈负相关。综上所述，我们的研究表明，无论是否存在HCC，HCV都会升高PCSK9水平。
