Clinical and virological features of occult hepatitis B in patients with HBsAg seroclearance post-treatment or spontaneously

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Occult hepatitis B virus (HBV) infection (OHB) may exist in patients experiencing hepatitis B surface antigen (HBsAg) seroclearance.


We examined the clinical and virological features of OHB in patients who lost HBsAg post-treatment or spontaneously.


We collected 44 patients with HBsAg seroclearance: 15 patients with dual HBV/hepatitis C virus (HCV) infection who lost HBsAg after peginterferon alfa-2a (PEG-IFN) plus ribavirin therapy; 13 HBV mono-infected patients who lost HBsAg after various oral antiviral therapies; and 16 patients who lost HBsAg spontaneously. OHB was defined as detectable serum HBV DNA in the absence of HBsAg. Viral mutations associated with OHB were identified by comparison with matched controls that remained positive for HBsAg, and further characterized in vitro.


The prevalence of OHB was 34.1% (15/44) in all patients, which was not significantly different among three groups. One mutation in surface promoter/polymerase region, C3050T (preS1T68I), was identified to be associated with the seroclearance of HBsAg in six cases. This mutation does not change the amino acid sequence of the polymerase protein. The S promoter activity was significantly lower in the construct containing C3050T mutation as compared with the wild-type (P = 0.0008). However, this mutation did not affect HBV replication, transcription and translation in the context of the full-length HBV genome. OHB was not rare in patients with HBsAg seroclearance.


One mutation, C3050T (preS1T68I), decreased S promoter activity; nevertheless, other factors may play more important role in the clearance of HBsAg in these OHB patients.

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