|
- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30437
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
本帖最后由 StephenW 于 2021-3-14 18:23 编辑
Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment
Man-Fung Yuen # 1 , Danny Ka-Ho Wong # 2 , Thomas Schluep 3 , Ching-Lung Lai 2 , Carlo Ferrari 4 , Stephen Locarnini 5 , Regina Cheuk-Lam Lo 6 7 , Robert G Gish 8 , James Hamilton 3 , Christine I Wooddell 9 , Lung Yi Mak 2 , Bruce D Given 3
Affiliations
Affiliations
1
Department of Medicine, The University of Hong Kong, Hong Kong, China [email protected].
2
Department of Medicine, The University of Hong Kong, Hong Kong, China.
3
Arrowhead Pharmaceuticals, Pasadena, California, USA.
4
Unit of Infectious Diseases and Hepatology, University of Parma, Parma, Italy.
5
Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia.
6
The University of Hong Kong, Hong Kong, Hong Kong.
7
Department of Pathology, The University of Hong Kong, Hong Kong, China.
8
Hepatitis B Foundation, Doylestown, PA, USA.
9
Arrowhead Pharmaceuticals, Madison, Wisconsin, USA.
#
Contributed equally.
PMID: 33712437 DOI: 10.1136/gutjnl-2020-323445
Abstract
Objective: We examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520.
Design: The present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4-9 4 weekly doses of MD ARC-520 and entecavir. Liver biopsies were performed in six patients. Intrahepatic and serum HBV DNA, HBV RNA and viral antigens were measured.
Results: All patients had 28.9-30.4 months of follow-up after the last MD. All three hepatitis B e antigen (HBeAg)-positive patients had profound reductions in hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen and HBV RNA with two undergoing HBeAg seroconversion. One further achieved HBsAg seroconversion (anti-HBs level of 25.1 IU/L) and the remaining two had HBsAg reductions of -1.7 and -3.5 log IU/mL >30 months after MD. Among the five HBeAg-negative patients, four had modest HBsAg reduction >29 months after completion of MD and one achieved HBsAg seroconversion (anti-HBs level of 152.5 IU/L) and was negative for liver HBsAg staining. Entecavir was successfully stopped in this patient 12 months after HBsAg seroconversion. Temporally related alanine aminotransferase elevations preceded by HBsAg reductions were observed in three patients suggesting immune activation. HBcAg staining was negative in all six biopsied patients. Two patients with <10% HBsAg positive staining of hepatocytes had correspondingly low serum HBsAg levels of 1.5 and 11.5 IU/mL.
Conclusions: MD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable.
Trial registration number: NCT02065336.
Keywords: hepatitis B.
© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ. |
|
发表于 2021-3-14 18:06
