Molecular Mechanisms Responsible for Occult Hepatitis B Virus Infection

Occult hepatitis B virus (HBV) infection (OBI); the presence of HBV DNA in the absence of HBsAg, has been recognized as one of the possible phases in the natural history of chronic HBV infection. OBI is a known clinical entity in some clinical settings including blood transfusion, cryptogenic cirrhosis, dialysis patients, solid transplantation, etc. The molecular basis of OBI is closely related to the peculiar life cycle of the HBV, and in particular to the long-lasting persistence of HBV covalently closed circular DNA (cccDNA) organized as a minichromosome into the nucleus of the infected hepatocytes. This feature together with the long half-life of liver cells imply that HBV infection, once occurred may continue for life, even in condition of strong inhibition of viral transcription and replication. In addition to cccDNA stability, other factors such as immune responses, viral mutations, epigenetic mechanisms, and co-infection are associated with occult infection. Importantly, all the conditions inducing host immunosuppression (i. e. , hematological malignancies, chemo-or immunotherapies, etc.) can cause the reactivation of OBI with the development of a typical overt hepatitis B infection.