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目的采用干扰素和阿德福韦酯治疗慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异,比较两种治疗策略的临床疗效。方法选择2002年2月2008年12月经100mg拉米夫定治疗后出现YMDD变异的慢性乙型肝炎患者76例。其中,男52例,女24例;年龄18～55岁,平均年龄33岁。服用100mg拉米夫定52～156周发生YMDD变异,HBVDNA低于治疗前水平,丙氨酸转移酶(alanine aminotransferase,ALT)<2×ULN/L患者分为A组(26例),继续用100mg拉米夫定治疗48周;服用100mg拉米夫定52～156周发生YMDD变异,HBVDNA定量检测高于或等于治疗前水平,ALT>2×ULN/L,根据患者自愿分为B组(27例)和C组(23例)。B组用100mg拉米夫定联合10mg阿德福韦酯治疗48周;C组用干扰素治疗48周。分别观察3组ALT复常率及HBVDNA转阴率、HBeAg阳性患者血清学转换率。结果治疗48周时,B、C组患者ALT复常率分别是74.1%和78.3%,明显高于A组的34.6%,差异有统计学意义(P<0.05);B、C组患者HBVDNA转阴率分别是77.7%和73.9%,明显高于A组的11.5%,差异有统计学意义(P<0.05);3组HBeAg阳性患者血清学转换率比较,差异均无统计学意义(P>0.05)。结论慢性乙型肝炎患者经拉米夫定治疗后出现YMDD变异,继续用拉米夫定治疗疗效不理想,改用干扰素或联合阿德福韦酯治疗更安全有效。
Objective To investigate the clinical efficacy of interferon and adefovir dipivoxil in the treatment of chronic hepatitis B patients after lamivudine treatment YMDD mutation. Methods Sixty-six patients with chronic hepatitis B who had YMDD mutation after 100 mg lamivudine treatment in December 2002 and December 2008 were selected. Among them, 52 males and 24 females; aged 18 to 55 years old, with an average age of 33 years. YMDD mutation occurred in 52 to 156 weeks after taking 100 mg lamivudine, HBVDNA was lower than pre-treatment level, and patients with alanine aminotransferase (ALT) <2 × ULN / L were divided into group A (26 cases) 100mg lamivudine treatment for 48 weeks; take 100mg lamivudine YMDD mutation occurs 52 to 156 weeks, HBVDNA quantitative detection is higher than or equal to the pre-treatment level, ALT> 2 × ULN / L, according to the patient voluntarily divided into group B 27 cases) and group C (23 cases). Group B with lamivudine 100mg 10mg adefovir dipivoxil treatment for 48 weeks; Group C with interferon for 48 weeks. The ALT normalization rate, HBVDNA negative rate and HBeAg positive rate were observed in 3 groups. Results At week 48, the rates of abnormal ALT in group B and group C were 74.1% and 78.3%, respectively, which were significantly higher than those in group A (34.6%, P <0.05) The negative rates were 77.7% and 73.9%, respectively, which were significantly higher than those in group A (11.5%) (P <0.05). There was no significant difference in seroconversion rate among the three HBeAg positive patients (P> 0.05). Conclusion YMDD mutation occurs in patients with chronic hepatitis B after lamivudine treatment. The treatment with lamivudine continues to be ineffective, and the treatment with interferon or adefovir dipivoxil is more safe and effective.