Ichikawa Tatsuki, Miyaaki Hisamitsu, Miuma Satoshi, Taura Naota, Motoyoshi Yasuhide, Akahoshi Hiroshi, Nakamura Junpei, Takahashi Youichi, Honda Tetsurou, Yajima Hiroyuki, Uehara Ryouhei, Hino Naoyuki, Narita Syouhei, Tanaka Hisaya, Sasaki Seina, Nakao Kazuhiko
Department of Gastroenterology, Nagasaki Harbor Medical Center, Nagasaki 850-8555, Japan.
Innovation and Translational Research Center, Nagasaki Harbor Medical Center, Nagasaki 850-8555, Japan.
Biomed Rep. 2019 Mar;10(3):156-164. doi: 10.3892/br.2019.1189. Epub 2019 Feb 4.
The present study evaluated the changes in lipid profile, and the associations between serum protein convertase subtilisin/kexin 9 (PCSK9), microRNA (miR)122 and low-density lipoprotein variation following treatment of hepatitis C virus (HCV) genotype 1b infection with Daclatasvir/Asunaprevir. A total of 39 patients with HCV genotype 1b infection with chronic hepatitis received a 24-week treatment regimen of Daclatasvir/Asunaprevir. Laboratory data were obtained for each subject every 4 weeks during treatment and every 12 weeks after treatment. Serum miR122 and PCSK9 were measured at the start of treatment (week 0), end of treatment (week 24), 4 weeks after the end of treatment (week 28), 12 weeks after the end of treatment (week 36) and 28 weeks after the end of treatment (week 52). LDL was increased at week 4 after the start of treatment to week 52. The increased LDL/HDL ratio at week 52 compared with week 4 was also associated with relative miR122 at week 52. At week 4, PCSK9-active form (A) was lower than that at other time points, and PCSK9-inactive form (I) exhibited the greatest increase. At week 52, PCSK9-A was higher than that during treatment, but PCSK9-I level at week 52 did not markedly differ from that any time point except for week 4. Relative miR122 at week 4 was associated with increased PCSK9-A at weeks 36 and 52 from the start of DAA. In summary, treatment of HCV with Daclatasvir/Asunaprevir resulted in elevated LDL, and relative miR122 and PCSK9-A levels in serum appeared to have some association with LDL increase.
本研究评估了使用达卡他韦/阿舒瑞韦治疗丙型肝炎病毒（HCV）1b型感染后血脂谱的变化，以及血清蛋白酶枯草杆菌蛋白酶/kexin 9型（PCSK9）、微小RNA（miR）122与低密度脂蛋白变化之间的关联。总共39例慢性丙型肝炎1b型感染患者接受了为期24周的达卡他韦/阿舒瑞韦治疗方案。在治疗期间每4周以及治疗后每12周获取每位受试者的实验室数据。在治疗开始时（第0周）、治疗结束时（第24周）、治疗结束后4周（第28周）、治疗结束后12周（第36周）以及治疗结束后28周（第52周）测量血清miR122和PCSK9。从治疗开始后第4周到第52周，低密度脂蛋白（LDL）升高。与第4周相比，第52周时升高的LDL/高密度脂蛋白（HDL）比值也与第52周时的相对miR122相关。在第4周时，PCSK9活性形式（A）低于其他时间点，而PCSK9非活性形式（I）升高幅度最大。在第52周时，PCSK9 - A高于治疗期间，但第52周时PCSK9 - I水平与除第4周外的任何时间点相比均无明显差异。从直接抗病毒药物（DAA）治疗开始，第4周时的相对miR122与第36周和第52周时PCSK9 - A升高相关。总之，使用达卡他韦/阿舒瑞韦治疗HCV导致LDL升高，血清中相对miR122和PCSK9 - A水平似乎与LDL升高存在一定关联。
