核苷类似物具有较强的抑制HBV复制的作用，拉米夫定抑制HBV DNA聚合酶，从而有效抑制HBV的复制。阿德福韦酯口服后最终在细胞内转化为阿德福韦双磷酸酯，后者可选择性抑制HBV DNA聚合酶。研究发现，对拉米夫定治疗的疗效及停药后疗效的持久性基因B型明显较C型好，而对拉米夫定耐药性的发生率基因型A高于D。Kao等对31例HBeAg阳性慢性乙肝患者经拉米夫定治疗后，B、C型的HBeAg血清转换率分别为23％和11％，耐药发生率分别为15％和22％，提示B型对拉米夫定的病毒学应答率高于C型。Suzuki等对日本234例用拉米夫定治疗的研究结果提示B型对拉米夫定的生化学和病毒学应答率均高于C型。目前众多临床研究发现，长期使用拉米夫定可引起HBV耐药或病毒变异，常见的变异为YMDD变异(包括YIDD和YVDD变异)。Zollner等研究发现，出现YIDD变异者，D型中有67%，A型中有19%，而出现YVDD变异者，A型中有81%，D型中有33%，提示不同的基因型可能对YMDD变异产生不同的影响。但是，Yuen等对中国慢性乙肝患者的研究发现，HBV基因型B和C对抗病毒治疗的反应及YMDD变异的发生率均无差别。目前，Westland等、Westland等研究表明，阿德福韦酯抗病毒疗效与HBV基因型、HBeAg及种族均没有明显相关性。
总之，HBV基因型与病毒复制与清除、病毒变异、临床表现、治疗应答和预后均有一定的关系，提示不同基因型具有不同的致病性。基因分型的研究为乙肝病毒变异的研究、发病机制的探讨、病情评估、治疗药物的选择和预后判定以及分子流行病学研究提供了有力工具。
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