Your browser doesn't support javascript.
loading
Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B.
Lai, Ching-Lung; Wong, Danny; Ip, Philip; Kopaniszen, Malgorzata; Seto, Wai-Kay; Fung, James; Huang, Fung-Yu; Lee, Brian; Cullaro, Giuseppe; Chong, Chun Kong; Wu, Ringo; Cheng, Charles; Yuen, John; Ngai, Vincent; Yuen, Man-Fung.
Afiliación
  • Lai CL; Department of Medicine, The University of Hong Kong, Hong Kong; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong. Electronic address: hrmelcl@hku.hk.
  • Wong D; Department of Medicine, The University of Hong Kong, Hong Kong; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong. Electronic address: dannykhwong@gmail.com.
  • Ip P; Department of Pathology, The University of Hong Kong, Hong Kong.
  • Kopaniszen M; Department of Medicine, The University of Hong Kong, Hong Kong.
  • Seto WK; Department of Medicine, The University of Hong Kong, Hong Kong; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.
  • Fung J; Department of Medicine, The University of Hong Kong, Hong Kong; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.
  • Huang FY; Department of Medicine, The University of Hong Kong, Hong Kong.
  • Lee B; Johns Hopkins University School of Medicine, MD, USA.
  • Cullaro G; Department of Medicine, Columbia University Medical Campus, New York City, NY, USA.
  • Chong CK; Department of Medicine, The University of Hong Kong, Hong Kong.
  • Wu R; Department of Medicine, The University of Hong Kong, Hong Kong.
  • Cheng C; Department of Medicine, The University of Hong Kong, Hong Kong.
  • Yuen J; Department of Medicine, The University of Hong Kong, Hong Kong.
  • Ngai V; Department of Medicine, The University of Hong Kong, Hong Kong.
  • Yuen MF; Department of Medicine, The University of Hong Kong, Hong Kong; State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong.
J Hepatol ; 66(2): 275-281, 2017 02.
Article en En | MEDLINE | ID: mdl-27639844
ABSTRACT
BACKGROUND AND

AIMS:

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), a mini-chromosome essential for HBV replication, is supposed to be resistant to nucleos(t)ide analogue treatment. We investigated the effect of long-term nucleos(t)ide analogue treatment on cccDNA.

METHODS:

Among 129 patients who had been enrolled in previous international nucleos(t)ide analogue clinical trials and had liver biopsies at baseline and one year after treatment, we recruited 43 patients on long-term continuous treatment for 72 to 145months for a third liver biopsy. Serum HBV DNA, hepatitis B surface antigen (HBsAg) levels, total intrahepatic HBV DNA (ihHBV DNA), cccDNA, HBV pregenomic RNA (pgRNA) as well as histologic changes were examined.

RESULTS:

At the time of the third biopsy, serum HBV DNA levels were undetectable in all but one patient. The median levels of HBsAg, ihHBV DNA, and cccDNA were 2.88logIU/ml, 0.03copies/cell, and 0.01copies/cell, respectively. Compared to baseline levels, there was reduction of HBsAg levels by 0.54log (71.46%), ihHBV DNA levels by 2.81log (99.84%), and cccDNA levels by 2.94log (99.89%), with 49% having cccDNA levels below the detection limit. One patient had undetectable HBsAg. The median pgRNA level, measured only in the third biopsy, was 0.021copies/cell, with 40% of patients having undetectable pgRNA.

CONCLUSIONS:

Long-term nucleos(t)ide analogue treatment induced marked depletion of cccDNA in the majority of patients while serum HBsAg levels, though reduced, were detectable in all but one patient. Whether cccDNA depletion is sustained and associated with better patient outcome requires further study. LAY

SUMMARY:

It is generally presumed that a form of hepatitis B virus DNA, called covalently closed circular DNA (cccDNA), which hides inside the nuclei of liver cells of patients with chronic hepatitis B, cannot be reduced by antiviral treatment. The present study showed that with prolonged treatment (median period 126months), cccDNA can be markedly reduced, with 49% of liver biopsies having undetectable cccDNA. This suggests that viral replication capacity would be very low after prolonged antiviral treatment.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 1_ASSA2030 / 2_ODS3 Problema de salud: 1_doencas_transmissiveis / 2_enfermedades_transmissibles / 2_muertes_prematuras_enfermedades_notrasmisibles Asunto principal: Antivirales / Virus de la Hepatitis B / Hepatitis B Crónica / Hígado Límite: Female / Humans / Male / Middle aged Idioma: En Revista: J Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2017 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 1_ASSA2030 / 2_ODS3 Problema de salud: 1_doencas_transmissiveis / 2_enfermedades_transmissibles / 2_muertes_prematuras_enfermedades_notrasmisibles Asunto principal: Antivirales / Virus de la Hepatitis B / Hepatitis B Crónica / Hígado Límite: Female / Humans / Male / Middle aged Idioma: En Revista: J Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2017 Tipo del documento: Article
...