Appearance of HbeAg in an Occult Persistent Hepatitis B Virus Infection

Occult hepatitis B virus infection (OBI) is characterized by the presence of ongoing viral replication with very low levels of viremia (<200 IU/ml), and negativity for HBsAg, while the so-called 'false' OBI with higher levels of HBV-DNA that are negative for HBsAg are usually due to the occurrence of mutations of the HBsAg sequence that may alter the recognition by some immunoassays. We describe here a case of occult HBV infection that combines both aspects. A male patient with severe systemic diseases, positive for anti-HBc and anti-HBs and negative for all other HBV markers, including HBsAg, since at least 4 years, showed a positivity for HBeAg at a follow-up control in November 2008; HBV-DNA testing by real-time PCR evidenced very low levels of viremia (<40 IU/ml), direct sequencing of the surface antigen-coding and Pol/RT coding regions allowed the identification of genotype D, serotype adw2, one immune escape mutation (G145R) and no drug resistance mutations. The positivity for HBeAg could be attributed to a superinfection in a naturally immune subject or to reactivation of a latent infection; the mutated virus had a reduced fitness and was therefore able to replicate only at low levels, resulting in a mild form of occult HBV infection.