Hepatitis B vaccine non-response and occult hepatitis B virus infection

Aims: Low levels of HBV DNA can remain detectable after serological recovery from Hep. B. This so called occult HBV infection is thought to maintain HBV-specific T-cell responses witch in turn is preventing HBV reactivation. However HCV-specific CTLs may also target B-cells presenting HBV antigens and thereby inhibiting the production of antibodies. In mouse models it has been shown that this mechanism can lead to an impaired humeral immune response.

Aims: We here hypothesized that non-response to HBV-vaccination could be linked to occult hepatitis B virus infection via HBV-specific T-cell responses targeting B-cells.

Methods: 43 otherwise healthy individuals with non-response (N=18; anti-HBs <10 IU/L after 3 doses of standard vaccination against hepatitis B at months 0, 1, and 6) or suboptimal response (N=25; anti-HBs 11–50 IU/L) were studied. They were all HBs-antigen and anti-HBc negative. HBV DNA was investigated by Arthus HBV Real-Time PCR, (Abbott Molecular Diagnostics, Wiesbaden, Germany) with detection limit 4 IU/ml.

Results: Only two subjects tested DNA positive in serum with HBV DNA levels of 1960 and 130 IU/ml respectively. The latter patient was tested two additional times and HBV viremia could be confirmed. The patient had received additional rounds of vaccinations, witch were all unsuccessful. This individual was also studied for HBV-specific T-cell responses. Interestingly HBV infection could be confirmed as he did not only mount an HBsAg-specific IFN-gamma response but also HBcore-specific T-cell response.

Conclusions: Hepatitis B vaccine non-response may be associated in single cases with occult hepatitis virus infection. Whether HBV-specific T-cell responses contribute to the failure of developing antibodies against HBV antigens needs to be investigated in larger studies.