AASLD2019[702]的安全性，耐受性和抗病毒活性 LEDIPASVIR / SOFOSBUVIR

StephenW

702
SAFETY, TOLERABILITY, AND ANTIVIRAL ACTIVITY OF
LEDIPASVIR/SOFOSBUVIR FOR HEPATITIS B INFECTION.
Angie S. Price, Amy Nelson, John Woo, Shyam Kottilil and
Joel Chua, Division of Clinical Care and Research, Institute of
Human Virology, University of Maryland School of Medicine,
Baltimore, MD, USA
Background: Current therapies against hepatitis B (HBV)
can achieve hepatitis B surface antigen (HBsAg) loss only
in a very small proportion of patients Previously published
data showed a modest reduction in HBsAg levels when
patients coinfected with both HBV and hepatitis C (HCV)
were treated with 12 weeks of ledipasvir/sofosbuvir (LDV/
SOF). We conducted a proof-of-concept study to determine
if these unexpected observations can be replicated in a
monoinfected CHB population treated with LDV/SOF for
12 weeks. The primary and secondary efficacy endpoint is
the change from baseline to end of the 12 week therapy in
serum HBsAg (in log10 IU/mL) and HBV DNA (in log10 IU/mL),
respectively Methods: This phase 2, single site, open-label,
interventional pilot study evaluated the safety, tolerability,
and antiviral activity of LDV/SOF for the treatment of HBV.
Eligible participants were adults with monoinfected CHB
who are not on antiviral therapy and do not require therapy
All enrolled subjects received fixed dose combination LDV
(90mg) / SOF (400mg) once daily for 12 weeks, and were
followed for an additional 12 weeks posttreatment Results:
Eight subjects were enrolled – median age of 41 years (range
30-53), majority (7 of 8) were male, and 50% were black All
were HBeAg negative and normal baseline ALT The baseline
HBsAg ranged from 172 1 to 15,489 6 IU/mL (mean 6,348 9
IU/mL), while baseline HBV DNA was between 90 to 1,660 IU/
mL (mean 734 IU/mL) All related adverse events (AE) were
mild Most common related AE was headache (2 of 8) There
were no serious AE, no discontinuation due to AE, or hepatitis
flare. Only one subject had mild transient asymptomatic
increase in alanine aminotransferase (ALT) level All 8 enrolled
subjects completed the study The mean HBsAg Log10 decline
(from baseline) at end of treatment was 0 399 log10 IU/mL,
while the mean HBV DNA decline at this same time point was
0 473 log10 IU/mL. Half (4 of 8) had HBsAg decline >0.5 log10
IU/mL with largest decline of 0 662 log10 IU/mL Similarly, 4 of
8 (50%) had HBV DNA decline >1.0 log10 IU/mL with largest
decline of 1 356 log10 IU/mL. HBsAg and HBV DNA levels
returned to baseline posttreatment (Figure 1) Conclusion:
Ledipasvir/sofosbuvir when given for 12 weeks is safe and
well tolerated by patients with monoinfected chronic HBV
infection and appears to have a modest antiviral activity
against hepatitis B.

StephenW

702
的安全性，耐受性和抗病毒活性
LEDIPASVIR / SOFOSBUVIR用于乙型肝炎感染。
安吉·普莱斯（Angie S. Price），艾米·纳尔逊（Amy Nelson），吴宇森，Shyam Kottilil和
蔡（Joel Chua），美国临床医学研究所临床护理与研究系
马里兰大学医学院人类病毒学
美国马里兰州巴尔的摩
背景：目前针对乙型肝炎（HBV）的疗法
只能达到乙型肝炎表面抗原（HBsAg）丢失
在极少数患者中
数据显示HBsAg水平适度降低时
同时感染HBV和C型肝炎（HCV）的患者
接受12周的ledipasvir / sofosbuvir（LDV /
SOF）。我们进行了概念验证研究，以确定
如果这些意外的发现可以复制到
用LDV / SOF治疗的单一感染CHB人群
12周主要和次要疗效终点是
从基线到12周治疗结束时的变化
血清HBsAg（log10 IU / mL）和HBV DNA（log10 IU / mL），
分别为方法：此阶段2，单点，开放标签，
介入性试验研究评估了安全性，耐受性，
LDV / SOF对乙肝的抗病毒和抗病毒活性。
符合条件的参与者是患有单一感染性CHB的成人
不接受抗病毒治疗且不需要治疗的人
所有入选的受试者均接受固定剂量的LDV组合
（90mg）/ SOF（400mg）每天一次，持续12周，并且
随后再治疗12周，结果：
招募了八名受试者–中位年龄为41岁（范围
30-53），多数（8名中的7名）是男性，而50％是黑人所有
HBeAg阴性且基线ALT正常
HBsAg范围为172 1至15,489 6 IU / mL（平均6,348 9
IU / mL），而基线HBV DNA在90至1,660 IU / mL之间
mL（平均734 IU / mL）所有相关不良事件（AE）为
轻度最常见的AE是头痛（8之2）
没有严重的AE，没有因AE停药或肝炎
耀斑。仅一名受试者轻度短暂无症状
丙氨酸氨基转移酶（ALT）水平升高所有8位已注册
受试者完成了研究HBsAg Log10平均下降
治疗结束时（相对于基线）（0 399 log10 IU / mL），
而同一时间点的平均HBV DNA下降是
0 473 log10 IU / mL。一半（8之4）的HBsAg下降> 0.5 log10
IU / mL，最大下降量为0662 log10 IU / mL
8（50％）的HBV DNA下降> 1.0 log10 IU / mL，最大
下降1356 log10 IU / mL。 HBsAg和HBV DNA水平
返回基线后治疗（图1）结论：
Ledipasvir / sofosbuvir服用12周后是安全的，
单一感染的慢性HBV患者耐受性良好
感染并且似乎具有适度的抗病毒活性
抗乙型肝炎。