ABSTRACT
It is known that hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists in the nucleus of infected hepatocytes in the form of minichromosome and is difficult to target and eliminate. Studies on the mechanisms and strategies for persistent silencing or elimination of HBV cccDNA are the focus achieving for “functional cure” of chronic hepatitis B. This article introduces the current knowledge on the basic biological features of cccDNA, regulatory mechanisms of transcription and metabolism, and related host factors, with a focus on the potential pathways and strategies for cccDNA silencing or elimination.
ABSTRACT
At present, interferon (IFN) and nucleos(t)ide analogues (NAs) remain the most important methods for the treatment of chronic hepatitis B in clinical practice, but neither of them can effectively eliminate the virus and cure hepatitis B. As the template for HBV transcription and replication, HBV covalently closed circular DNA (cccDNA) persistently exists in the nucleus in the form of minichromosome and is considered the most important reason for chronic and refractory HBV infection. Since it is hard to completely eliminate cccDNA, functional cure of chronic hepatitis B through sustained silencing of cccDNA has become a major goal of clinical and basic research in recent years. This article reviews the influence of current treatment methods on cccDNA, the factors regulating the amount and activity of cccDNA, and the key obstacles to eradication of cccDNA pool, with perspectives of cccDNA research towards a functional cure of chronic hepatitis B.