Occult hepatitis B infection.

Occult hepatitis B virus (HBV) infection (OBI) is recognized as one of the possible phases in the natural history of chronic HBV infection [1]. OBI defines the persistence of HBV genomes in the hepatocytes of individuals testing negative for HBV surface antigen (HBsAg) and, usually, also for serum HBV DNA [2]. Apart from some cases in which the lack of HBsAg detection is attributable to the HBV genetic heterogeneity (i.e., infection with replication-defective variants or with S-escape mutants producing a modified HBsAg undetectable by diagnostic kits), in most cases OBI is related to replication-competent viruses that are strongly suppressed in their activities (replicative and transcriptional) by the host’s defense mechanisms. Very importantly, this suppression (a) does not have an absolute effect and residual, low-levels of replication and transcription may persist over time, and (b) may be reversible in particular circumstances leading to viral reactivation and development of a typical HBsAg-positive (namely, “overt”) infection