Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
J Med Virol. 2023 Jan;95(1):e28105. doi: 10.1002/jmv.28105. Epub 2022 Sep 12.
Retrospective data showed that when we administered ledipasvir/sofosbuvir (LDV/SOF) to patients with hepatitis B and C coinfection, there was a modest reduction in hepatitis B surface antigen (HBsAg). Therefore, we hypothesize that similar HBsAg reduction can be seen in hepatitis B virus (HBV) monoinfected subjects. Primary and secondary efficacy endpoints are the decline in HBsAg and HBV DNA at Week 12 from baseline, respectively. We conducted an open-label Phase 2 pilot study to evaluate the safety, tolerability, and antiviral activity of LDV and/or SOF for HBV. Eligible subjects were either suppressed on antivirals (Group B) or inactive chronic HBV (Group A, C, D). Group A and B received LDV/SOF. Group C and D received SOF 400 mg and LDV 90 mg, respectively. All subjects completed the study, and all related adverse events (AEs) were mild. No discontinuations due to AEs or hepatitis flare occurred. At Week 12, HBsAg decline (log IU/ml) was similar between Group A (0.399) and B (0.400), less in Group C (0.207), and none in Group D, and there was HBV DNA decline in the inactive chronic HBV groups. LDV and SOF are safe and well tolerated when given to chronic hepatitis B subjects and have modest antiviral activity, particularly when given in combination.
回顾性数据显示，当我们给乙型肝炎和丙型肝炎合并感染的患者使用 ledipasvir/sofosbuvir（LDV/SOF）时，乙型肝炎表面抗原（HBsAg）略有下降。因此，我们假设在乙型肝炎病毒（HBV）单感染患者中也可以看到类似的 HBsAg 下降。主要和次要疗效终点分别是基线时第 12 周 HBsAg 和 HBV DNA 的下降。我们进行了一项开放标签的 2 期试点研究，以评估 LDV 和/或 SOF 治疗 HBV 的安全性、耐受性和抗病毒活性。符合条件的受试者要么在抗病毒药物治疗下得到抑制（B 组），要么患有非活动慢性 HBV（A、C、D 组）。A 组和 B 组接受 LDV/SOF。C 组和 D 组分别接受 SOF 400mg 和 LDV 90mg。所有受试者均完成了研究，所有相关不良事件（AE）均为轻度。没有因 AE 或肝炎发作而停药的情况。第 12 周时，A 组（0.399）和 B 组（0.400）的 HBsAg 下降（log IU/ml）相似，C 组（0.207）下降较少，D 组则没有，非活动慢性 HBV 组的 HBV DNA 下降。当给予慢性乙型肝炎患者时，LDV 和 SOF 安全且耐受良好，具有适度的抗病毒活性，特别是联合使用时。
