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乙型肝炎病毒（ HBV）全基因组克隆的体外培养可用来分析HBV变异株的结构和功能变化。利用该方法发现，HBV表面抗原129L突变体具有正常的抗-HBs结合效率，但其降低了免疫原性，从而导致HBV的持续感染；来自重型乙型肝炎患者的HBV株并不都具有高复制效率，其诱导抗-HBs的能力可能与重型乙型肝炎的发病机制有关；来自肝癌患者的 HBV 株的高效复制可能是宿主免疫病理反应增强的原因；HBV耐药突变并非都引起病毒反弹，仅根据病毒载量监测药物治疗失败可能导致误判。“,”Structural and functional changes of HBV variants could be investigated by vitro culturing of the full-genomic clones of these variants.By using this method,it has been found that HBV mutant 129L has the common efficiency of anti-HBs binding,but it reduces the immunogenicity which could lead to persistent HBV infection.HBV strains from fulminant hepatitis patients did not always replicate with high efficiency ,but their capability in inducing anti-HBs production could be associated with the pathogenesis of fulminant hepa-titis.The high replication activity of HBV isolates from patients with hepatocellular carcinoma may account for the exacerbation of immunopathological effects in the host .Drug-resistant mutations of HBV could not always bring about viral rebound,which may result in misdiagnosis of drug resistance if viral load is used as the only criterion for drug failure.