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Currently, there are two types of antiviral therapy for HBV infection: nucleoside/nucleotide analogs (NAs) and interferon (IFN). 2 The former suppresses HBV replication by inhibiting its polymerase; the latter does so by its direct antiviral effects as well as indirect modulation of the host immune response. Only a small portion of patients can undergo HBsAg seroclearance with antiviral therapy; this response has been associated with several host and viral factors. 3, 4 Unfortunately, viral rebound often occurs following discontinuation of antiviral therapy. 5, 6, 7 Accumulating evidence has proven that the persistence of covalently closed circular.