APASL2016 血清HBV-RNA水平与REP 2139-CA剂量慢性乙肝患者显著回落

StephenW

Serum HBV-RNA levels decline significantly in chronic hepatitis B patients dosed with REP2139-CA

Background and aims: The HBsAg release inhibitor REP2139-Ca may be a promising new treatment option for chronic hepatitis B (CHB) patients, however its effect on hepatitis B pregenomic RNA (HBV-RNA) is unknown. HBV-RNA levels during treatment with REP2139-Ca were determined and compared with HBV-DNA and HBsAg levels.
Methods: 12 Patients with HBeAg positive CHB participating in a phase 2 study were dosed with the nucleic-acid based amphipathic polymer REP2139-Ca for 20–38 weeks. Responders to REP2139 (defined as clearance of serum HBsAg) were subsequently treated with an add-on immunomodulatory agent (peginterferon alpha-2a and/or thymosin alpha-1). HBsAg, HBV-DNA, and HBV-RNA levels were determined at baseline, after 20–24 weeks of REP2139-Ca monotherapy, and either during a treatment-free follow-up (for responders) or during entecavir treatment (for non-responders). HBV- RNA was quantified by RT-qPCR using HBV-specific primers. Results: HBV-RNA levels were detectable in all 12 HBeAg-positive patients before treatment [mean 6.70 (SD 0.83) logC/mL], and were significantly associated with HBsAg (r2 0.33, p = 0.049) and HBV- DNA levels (r2 0.74, p \ 0.001). After 20–24 weeks of REP2139-Ca treatment, mean HBV-RNA, HBV-DNA, and HBsAg levels had declined significantly compared to baseline (all p \ 0.001). At week 20–24, HBV-RNA was undetectable in 8/12 patients. In 7 of these 8 patients, HBV-RNA remained undetectable during the treatment-free follow-up period (mean 21.9 weeks, range 7–27). HBsAg sero-con- version was achieved in 4/8 patients during follow-up (anti-HBs range 200–766 U/L).
Conclusions: In patients treated with REP2139-Ca, serum HBV-RNA levels declined significantly compared to baseline. REP2139-Ca may be a promising new treatment option for CHB patients.              

StephenW

血清HBV-RNA水平与REP 2139-CA剂量慢性乙肝患者显著回落
背景和目的：本HBeAg的释放抑制剂REP 2139钙可以是用于慢性乙型肝炎（CHB）的患者有希望的新的治疗选择，但其对乙型肝炎前基因组RNA的病毒（HBV-RNA）的效果是未知的。与REP2139钙治疗期间的HBV-RNA水平进行了测定，并与HBV-DNA和HBsAg水平进行比较。
方法：将12例HBeAg阳性CHB参加第二阶段的研究与核酸基于两亲性高分子REP2139钙为20-38周一起加料。响应者REP2139（定义为血清HBsAg清除）与附加免疫调节剂（聚乙二醇干扰素阿尔法-2a和/或胸腺素α-1）随后被处理。在基线测定的HBsAg，HBV-DNA和HBV-RNA水平，20-24周REP2139钙单一疗法后，并且无论在一个无治疗随访（用于应答者）或恩替卡韦治疗期间（对于无反应者）。 HBV-RNA，通过RT-qPCR的使用HBV特异性引物进行定量。结果：HBV-RNA水平在所有12例HBeAg阳性患者治疗检测[平均6.70（SD 0.83）logC /毫升]之前，与乙肝表面抗原（R2 0.33，P = 0.049）和HBV-DNA水平显著相关性（R2 0.74，第\ 0.001）。 20-24周REP2139钙的治疗后，平均HBV-RNA，HBV-DNA和HBsAg水平已经比较基准显著下降（均P \ 0.001）。在20-24周，HBV-RNA在8/12的患者检测不到。在这8例患者中7，HBV-RNA在无治疗随访期间（平均21.9周，范围7-27）仍无法检测。乙肝表面抗原血清CON-版本随访（抗-HBs范围200-766 U / L）期间4/8的患者实现。
结论：在与REP2139钙治疗的患者，血清HBV-RNA水平有所下降显著相比基线。 REP2139钙可能是慢性乙肝患者有前途的新的治疗选择。