Korenaga Masaaki, Murata Kazumoto, Izumi Namiki, Tamaki Nobuharu, Yokosuka Osamu, Takehara Tetsuo, Sakamoto Naoya, Suda Goki, Nishiguchi Shuhei, Enomoto Hirayuki, Ikeda Fusao, Yanase Mikio, Toyoda Hidenori, Genda Takuya, Umemura Takeji, Yatsuhashi Hiroshi, Yamasaki Kazumi, Ide Tatsuya, Toda Nobuo, Kanda Tatsuo, Nirei Kazushige, Ueno Yoshiyuki, Haga Hiroaki, Nishigaki Yoichi, Nakane Kunio, Omata Masao, Mochizuki Hitoshi, Aoki Yoshihiko, Imamura Masatoshi, Kanto Tatsuya, Mizokami Masashi
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan.
Glob Health Med. 2022 Aug 31;4(4):216-224. doi: 10.35772/ghm.2022.01026.
It is well-known that sustained virological response (SVR) by interferon (IFN)-based therapy against hepatitis C virus (HCV) infection reduced the incidence of hepatocellular carcinoma (HCC). However, whether IFN-free direct-acting antivirals reduce the risk of HCC is controversial. Therefore, this study aims to compare the incidence of HCC after the achievement of SVR between sofosbuvir combined with ledipasvir (SOF/LDV) and simeprevir with pegylated interferon plus ribavirin (Sim+IFN). Japanese patients with HCV infection (genotype 1) who achieved SVR between January 2013 and December 2014 by SOF/LDV (NCT01975675, = 320) or Sim+IFN (000015933, = 289) therapy in two nationwide, multicenter, phase III studies were prospectively monitored for the development of HCC by ultrasonography for 5 years after the end of treatment (EOT). No HCC was detected before the treatment. HCC was detected in 9 and 7 patients in the SOF/LDV and the Sim+IFN group in 5 years, respectively. The cumulative incidences of HCC rates 1, 3, and 5 years after EOT were similar between the two groups (1.5%, 2.7%, and 3.2% for the SOF/LDV and 1.8%, 2.8%, and 3.0% for the Sim+IFN group, respectively). No HCC was developed 3.5 years after EOT. Interestingly, a retrospective careful review of imaging taken before therapy revealed hepatic nodules in 50% of HCC patients, suggesting HCC was pre-existed before therapy. In conclusion, we could not find any differences in the incidence of HCC after the HCV eradication between the two therapeutic regimens, suggesting no enhancement of HCC development by DAA.
众所周知，基于干扰素（IFN）的疗法对丙型肝炎病毒（HCV）感染实现持续病毒学应答（SVR）可降低肝细胞癌（HCC）的发病率。然而，不含干扰素的直接抗病毒药物是否能降低HCC风险仍存在争议。因此，本研究旨在比较索磷布韦联合来迪派韦（SOF/LDV）与simeprevir联合聚乙二醇干扰素加利巴韦林（Sim+IFN）实现SVR后HCC的发病率。在两项全国性、多中心、III期研究中，通过SOF/LDV（NCT01975675，n = 320）或Sim+IFN（000015933，n = 289）疗法于2013年1月至2014年12月实现SVR的日本HCV感染（基因1型）患者，在治疗结束（EOT）后通过超声前瞻性监测HCC发生情况达5年。治疗前未检测到HCC。5年内，SOF/LDV组和Sim+IFN组分别有9例和7例患者检测到HCC。两组EOT后1年、3年和5年HCC累积发病率相似（SOF/LDV组分别为1.5%、2.7%和3.2%，Sim+IFN组分别为1.8%、2.8%和3.0%）。EOT后3.5年未发生HCC。有趣的是，对治疗前影像学检查的回顾性仔细分析显示，50%的HCC患者存在肝结节，提示HCC在治疗前已存在。总之，我们未发现两种治疗方案在HCV根除后HCC发病率上存在差异，表明直接抗病毒药物不会增加HCC的发生。
