What do we know about occult hepatitis B virus infection?

Occult hepatitis B virus (HBV) infection (OBI) is recognized as one of the phases in the natural history of chronic HBV infection and defines the persistence of HBV genomes in the hepatocytes of individuals testing negative for HBV surface antigen (HBsAg) and detectable or undetectable HBV DNA in the serum. Occasionally, OBI is related to the infection with mutant viruses producing a modified HBsAg undetectable by diagnostic kits or with replication-defective variants. However, in most cases OBI is due to replication-competent viruses that are strongly suppressed in their activities by the host’s defence mechanisms. Growing evidence indicates that genetic, epigenetic and post-transcriptional mechanisms may be involved in the control of HBV activities and in the OBI occurrence. OBI may be involved in several different clinical contexts, which can be grouped in four main categories: 1) transmission of the “occult” virus (mainly, through blood transfusion and orthotopic liver transplantation from OBI donors) causing classic forms of hepatitis B in the HBV naïve recipients; 2) reactivation of the HBV infection following the development of an immunosuppressive status, resulting in acute and occasionally fulminant hepatitis; 3) contribution to the progression of patients with various causes of liver disease toward cirrhosis; 4) involvement in hepatocarcinogenesis, likely through the maintenance of the direct and indirect pro-oncogenic properties typical of the overt HBV infection (such as the capacity to integrate in the host’s genome and to synthesize pro-oncogenic proteins) and by provoking a mild but persisting necroinflammation which favours cirrhosis development