Statements from the Taormina expert meeting on occult hepatitis B virus infection☆

Occult hepatitis B virus infection (OBI)

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  Definition: Presence of HBV DNA in the liver (with detectable or undetectable HBV DNA in the serum) of individuals testing HBsAg negative by currently available assays.

  When detectable, the amount of HBV DNA in the serum is usually very low (<200 IU/ml).

  On the basis of the HBV antibody profile, OBI may be distinguished as:

  • Seropositive-OBI (anti-HBc and/or anti-HBs positive).

  • Seronegative-OBI (anti-HBc and anti-HBs negative).

  In seropositive-OBI subjects, serum HBsAg may become negative either

Virological and immunological aspects

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  The molecular basis of persistent OBI is related to the long-lasting persistence of HBV cccDNA in the nuclei of hepatocytes [4], [26], [41], [42], [43], [44], [45].

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  Almost all OBI cases are infected with replication-competent HBV showing strong suppression of overall replication activity and gene expression resulting in a significant reduced yield of HBV [4], [7], [9], [26], [46], [47].

  A small number of cases of OBI are due to infection with HBV mutants with defective replication activity or

Diagnosis of OBI and epidemiological aspects

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  HBV DNA is the only reliable diagnostic marker of OBI.

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  Key recommendation: OBI tests must be performed only on samples collected and stored under the most appropriate conditions for polymerase chain reaction (PCR) procedures, paying particular attention to avoid cross-contamination.

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  If highly sensitive HBV DNA testing is not feasible, anti-HBc should be used as a less than ideal surrogate marker for identifying potential seropositive OBI individuals in cases of blood, tissue or organ donation and

Clinical impact

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  HBsAg unreactive blood donations containing HBV DNA have to be considered infectious. As discussed above, the use of multivalent anti-HBs antibodies in the HBsAg detection kits is strongly recommended.

  The ability of HBV nucleic acid amplification testing (NAT) in detecting potentially infectious blood units before donation is clear nowadays. However, the real risk of transmission to recipients and the “cost/benefit ratio” of testing the blood of donors for OBI in terms of avoided morbidity and

Conclusions

Occult HBV infection is a complex biological entity with possible relevant clinical implications.

There are discordant data sets on several aspects of OBI, mainly reflecting the lack of methodological uniformity among the different studies, and varied technical approaches employed for the diagnosis of OBI. The goal of the Taormina meeting was to review the present knowledge on occult HBV and to identify the most appropriate ways that should be followed in future studies. Hopefully, these