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Persistently high viral antigen levels had been incriminated to result in the exhaustion of HBV-specific T cells15 and possibly dendritic cells and natural killer (NK) cells.16,17 The recovery of HBV-specific immune responses had been demonstrated in patients with spontaneous, IFNα-induced or NA-induced HBeAg or HBsAg loss.18–20 A recent study showed that HBV-specific T-cell responses were enhanced in some patients who experienced a marked decrease in HBsAg levels during siRNA therapy.21 These data suggest that sustained suppression of HBV DNA replication and HBsAg production may restore HBV-specific immune responses in some patients, but immune modulatory therapies may still be needed in others

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