Grimm Jonathan, Peschel Georg, Müller Martina, Schacherer Doris, Wiest Reiner, Weigand Kilian, Buechler Christa
Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious Diseases, University Hospital Regensburg, 93053 Regensburg, Germany.
Department of Visceral Surgery and Medicine, University Inselspital, 3010 Bern, Switzerland.
J Clin Med. 2021 Apr 11;10(8):1621. doi: 10.3390/jcm10081621.
Direct-acting antivirals (DAAs) efficiently eradicate the hepatitis C virus (HCV). Low-density lipoprotein (LDL) levels increase rapidly upon DAA treatment. Proprotein convertase subtilisin/kexin 9 (PCSK9) induces degradation of the hepatic LDL receptor and thereby elevates serum LDL. The aim of this study was to determine serum PCSK9 concentrations during and after DAA therapy to identify associations with LDL levels. Serum PCSK9 was increased in 82 chronic HCV-infected patients compared to 55 patients not infected with HCV. Serum PCSK9 was low in HCV patients with liver cirrhosis, but patients with HCV-induced liver cirrhosis still exhibited higher serum PCSK9 than patients with non-viral liver cirrhosis. Serum PCSK9 correlated with measures of liver injury and inflammation in cirrhotic HCV patients. In patients without liver cirrhosis, a positive association of serum PCSK9 with viral load existed. Serum PCSK9 was not different between viral genotypes. Serum PCSK9 did not correlate with LDL levels in HCV patients irrespective of cirrhotic status. Serum PCSK9 was reduced, and LDL was increased at four weeks after DAA therapy start in non-cirrhotic HCV patients. Serum PCSK9 and LDL did not change upon DAA treatment in the cirrhotic group. The rapid decline of PCSK9 after the start of DAA therapy in conjunction with raised LDL levels in non-cirrhotic HCV patients shows that these changes are not functionally related.
直接作用抗病毒药物（DAAs）能有效根除丙型肝炎病毒（HCV）。在接受DAA治疗后，低密度脂蛋白（LDL）水平会迅速升高。前蛋白转化酶枯草溶菌素/kexin 9（PCSK9）可诱导肝脏LDL受体降解，从而升高血清LDL水平。本研究的目的是测定DAA治疗期间及之后的血清PCSK9浓度，以确定其与LDL水平的相关性。与55例未感染HCV的患者相比，82例慢性HCV感染患者的血清PCSK9水平升高。肝硬化的HCV患者血清PCSK9水平较低，但HCV诱导的肝硬化患者的血清PCSK9水平仍高于非病毒性肝硬化患者。血清PCSK9与肝硬化HCV患者的肝损伤和炎症指标相关。在无肝硬化的患者中，血清PCSK9与病毒载量呈正相关。不同病毒基因型患者的血清PCSK9水平无差异。无论肝硬化状态如何，HCV患者的血清PCSK9与LDL水平均无相关性。在非肝硬化HCV患者中，DAA治疗开始四周后血清PCSK9降低，LDL升高。肝硬化组患者接受DAA治疗后血清PCSK9和LDL均无变化。非肝硬化HCV患者在DAA治疗开始后PCSK9迅速下降，同时LDL水平升高，这表明这些变化在功能上无相关性。
