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Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment.
Yuen, Man-Fung; Wong, Danny Ka-Ho; Schluep, Thomas; Lai, Ching-Lung; Ferrari, Carlo; Locarnini, Stephen; Lo, Regina Cheuk-Lam; Gish, Robert G; Hamilton, James; Wooddell, Christine I; Mak, Lung Yi; Given, Bruce D.
Afiliación
  • Yuen MF; Department of Medicine, The University of Hong Kong, Hong Kong, China mfyuen@hkucc.hku.hk.
  • Wong DK; Department of Medicine, The University of Hong Kong, Hong Kong, China.
  • Schluep T; Arrowhead Pharmaceuticals, Pasadena, California, USA.
  • Lai CL; Department of Medicine, The University of Hong Kong, Hong Kong, China.
  • Ferrari C; Unit of Infectious Diseases and Hepatology, University of Parma, Parma, Italy.
  • Locarnini S; Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia.
  • Lo RC; The University of Hong Kong, Hong Kong, Hong Kong.
  • Gish RG; Department of Pathology, The University of Hong Kong, Hong Kong, China.
  • Hamilton J; Hepatitis B Foundation, Doylestown, PA, USA.
  • Wooddell CI; Arrowhead Pharmaceuticals, Pasadena, California, USA.
  • Mak LY; Arrowhead Pharmaceuticals, Madison, Wisconsin, USA.
  • Given BD; Department of Medicine, The University of Hong Kong, Hong Kong, China.
Gut ; 71(4): 789-797, 2022 04.
Article en En | MEDLINE | ID: mdl-33712437
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis B Crónica Límite: Humans País/Región como asunto: Asia Idioma: En Revista: Gut Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Hepatitis B Crónica Límite: Humans País/Región como asunto: Asia Idioma: En Revista: Gut Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido