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Objective: To address HBV serum nucleic acid markers for stages without apparent replication. Methods: DNA and RNA sequence segments from the X, C and pre C/C regions produced successively during replication were used as targets for quantitative PCR and RT/PCR. Results: The assays confirmed the preferential formation of intermediates blocked at early stages. They persisted as the only detectable type of serum HBV DNA even after one year of therapy. At reentry into viral replication due to emergence of drug resistant mutants, lamivudine resistance produced exclusively incomplete DNA minus strands, whereas the wild type virus immediately synthesized complete DNA minus strands. Conclusion:PCR assays used for monitoring complete suppression of HBV replication must target the X gene region.