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Transition to HBeAg-negative chronic hepatitis B virus infection is associated with reduced cccDNA transcriptional activity.
Suslov, Aleksei; Meier, Marie-Anne; Ketterer, Sylvia; Wang, Xueya; Wieland, Stefan; Heim, Markus Hermann.
Afiliación
  • Suslov A; Department of Biomedicine, University Hospital Basel, University of Basel, Basel, CH-4031, Switzerland.
  • Meier MA; Department of Biomedicine, University Hospital Basel, University of Basel, Basel, CH-4031, Switzerland; Division of Gastroenterology and Hepatology, University Center for Gastrointestinal and Liver Diseases, Basel, CH-4002, Switzerland.
  • Ketterer S; Department of Biomedicine, University Hospital Basel, University of Basel, Basel, CH-4031, Switzerland.
  • Wang X; Department of Biomedicine, University Hospital Basel, University of Basel, Basel, CH-4031, Switzerland.
  • Wieland S; Department of Biomedicine, University Hospital Basel, University of Basel, Basel, CH-4031, Switzerland. Electronic address: stefan.wieland@unibas.ch.
  • Heim MH; Department of Biomedicine, University Hospital Basel, University of Basel, Basel, CH-4031, Switzerland; Division of Gastroenterology and Hepatology, University Center for Gastrointestinal and Liver Diseases, Basel, CH-4002, Switzerland. Electronic address: markus.heim@unibas.ch.
J Hepatol ; 74(4): 794-800, 2021 04.
Article en En | MEDLINE | ID: mdl-33188905
ABSTRACT
BACKGROUND &

AIMS:

HBeAg seroconversion during the natural history of chronic hepatitis B (CHB) is associated with a strong drop in serum HBV DNA levels and a reduction of intrahepatic covalently closed circular DNA (cccDNA) content. Of particular interest is the transition to HBeAg-negative chronic infection (ENCI). ENCI, previously known as inactive carrier state, is characterized by very low or negative viremia and the absence of liver disease. The molecular mechanisms responsible for the transition to ENCI and for the control of viral replication in ENCI are still poorly understood.

METHODS:

To identify which step(s) in the viral life cycle are controlled during the transition to ENCI, we quantified cccDNA, pre-genomic RNA (pgRNA), total HBV RNA and DNA replicative intermediates in 68 biopsies from patients in different phases of CHB.

RESULTS:

HBeAg seroconversion is associated with a reduction of cccDNA amounts as well as transcriptional activity. Silencing of cccDNA is particularly pronounced in ENCI, where there was ~46 times less pgRNA per cccDNA compared to HBeAg-negative CHB. Furthermore, a subgroup of patients with HBeAg-negative CHB can be characterized by reduced replication efficiency downstream of pgRNA.

CONCLUSIONS:

The reduction in serum viral load during the transition to ENCI seems to primarily result from strong inhibition of the transcriptional activity of cccDNA which can be maintained in the absence of liver disease. LAY

SUMMARY:

During the natural course of chronic hepatitis B virus infections, the immune response can gain control of viral replication. Quantification of viral DNA and RNA in liver biopsies of patients in different stages of chronic hepatitis B allowed us to identify the steps in the viral life cycle that are affected during the transition from active to inactive disease. Therapeutic targeting of these steps might induce sustained inhibition of viral transcription.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Replicación Viral / ADN Circular / Activación Transcripcional / Virus de la Hepatitis B / Hepatitis B Crónica / Transcripción Viral / Antígenos e de la Hepatitis B Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: J Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Suiza

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Replicación Viral / ADN Circular / Activación Transcripcional / Virus de la Hepatitis B / Hepatitis B Crónica / Transcripción Viral / Antígenos e de la Hepatitis B Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: J Hepatol Asunto de la revista: GASTROENTEROLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Suiza