Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Faculty of Internal Medicine and Hepatitis Research Center, School of Medicine, College of Medicine, and Center for Cancer Research and Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan.
PLoS One. 2021 Feb 4;16(2):e0245479. doi: 10.1371/journal.pone.0245479. eCollection 2021.
BACKGROUND/AIMS: Undetectable HCV RNA 12 weeks after the end of treatment (SVR12) has been the valid efficacy endpoint in the era of direct-acting antivirals (DAAs). Its concordance with SVR4 and SVR24 and long-term durability is unknown in Taiwanese chronic hepatitis C (CHC) patients.
A total of 1080 CHC patients who received all-oral DAAs and an achieved end-of-treatment virological response (EOTVR), defined as undetectable HCV RNA at the end of therapy, were consecutively enrolled. HCV RNA was monitored 4, 12, and 24 weeks after EOT. Patients who achieved SVR24, defined as undetectable HCV RNA 24 weeks after EOT, were followed annually for assessing SVR durability.
Eleven (1.02%) patients experienced HCV RNA reappearance after EOT. The most frequent timing of RNA reappearance was observed at SVR4 (n = 7), followed by SVR12 (n = 3) and SVR 24 (n = 1). The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 in predicting SVR12 were 99.7% and 100%, respectively, whereas the PPV and NPV of SVR12 in predicting SVR24 were 99.9% and 100%, respectively. Pyrosequencing confirmed delayed relapse rather than reinfection for the patient who had detectable HCV RNA at SVR24. Among 978 patients who achieved SVR24, after a median follow-up period of 17.3±8.2 months, the SVR durability is 100% up to a 4-year follow-up.
Achievement of SVR12 provides excellent durability of HCV seroclearance after DAA therapy. On-demand HCV RNA beyond SVR12 should be recommended for patients with unexplainable abnormal liver function or high-risk behaviors.
背景/目的:在直接作用抗病毒药物(DAA)时代,治疗结束后 12 周(SVR12)无法检测到 HCV RNA 已成为有效的疗效终点。然而,在台湾慢性丙型肝炎(CHC)患者中,其与 SVR4 和 SVR24 的一致性以及长期持久性尚不清楚。
共连续纳入 1080 例接受全口服 DAA 治疗且获得治疗结束病毒学应答(EOTVR)的 CHC 患者,EOTVR 定义为治疗结束时 HCV RNA 无法检测到。在 EOT 后 4、12 和 24 周监测 HCV RNA。达到 SVR24(定义为 EOT 后 24 周 HCV RNA 无法检测到)的患者每年进行一次随访,以评估 SVR 的持久性。
11 例(1.02%)患者在 EOT 后出现 HCV RNA 再次出现。RNA 再次出现的最常见时间是在 SVR4(n=7),其次是 SVR12(n=3)和 SVR24(n=1)。SVR4 预测 SVR12 的阳性预测值(PPV)和阴性预测值(NPV)分别为 99.7%和 100%,而 SVR12 预测 SVR24 的 PPV 和 NPV 分别为 99.9%和 100%。焦磷酸测序证实,对 SVR24 时可检测到 HCV RNA 的患者,发生的是延迟复发而非再感染。在 978 例达到 SVR24 的患者中,中位随访 17.3±8.2 个月后,直至 4 年随访时,SVR 持久性为 100%。
DAA 治疗后达到 SVR12 可提供 HCV 血清学清除的优异持久性。对于不明原因肝功能异常或高危行为的患者,应建议在 SVR12 后按需进行 HCV RNA 检测。