慢性乙型肝炎恩替卡韦治疗后的血清病毒学变化特征

目的研究恩替卡韦（ETV）治疗初治和拉米夫定（LAM）耐药慢性乙型肝炎（CHB）患者的病毒学应答和耐药。方法50例CHB患者按ETV治疗时机分2组：A组为ETV初治患者25例,患者口服ETV0.5mg/次,每日1次;B组为LAM耐药患者25例,患者口服ETV1.0mg/次,每日1次。疗程中监测患者肝功能和HBV DNA载量,在48周后HBV DNA仍大于4log10拷贝/ml或病毒学突破时,提取患者血清HBV DNA直接测序进行耐药变异分析。结果A组基线、12周、24周、48周、96周HBV DNA载量分别为（7.85±0.83）log10拷贝/ml、（3.24±0.97）log10拷贝/ml、（2.96±0.59）log10拷贝/ml、（2.86±0.52）log10拷贝/ml、（2.70±0）log10拷贝/ml;而B组基线、12周、24周、48周、96周HBV DNA载量分别为（6.41±1.43）log10拷贝/ml、（3.76±0.89）log10拷贝/ml、（2.72±0.09）log10拷贝/ml、（3.14±1.22）log10拷贝/ml、（3.04±1.06）log10拷贝/ml。A组DNA转阴率12周、24周、48周、96周分别为64.0%、80.0%、84.2%、94.4%,B组DNA转阴率12周、24周、48周、96周时分别为32.0%、68.0%、80.0%、88.2%。A组未发现ETV耐药变异,B组患者共有3例（12.0%）发生耐药,48周和96周ETV基因型耐药率分别为4.0%、12.0%。结论ETV治疗初治和LAM耐药患者均有较好病毒学应答,但LAM耐药患者较初治患者ETV累积耐药率高。

Virologic characteristics of entecavir in chronic hepatitis B patients

Objective To investigate the response and resistance of entecavir （ETV） in patients of ETV treatmentnaive or lamivudine-resistant hepatitis B virus. Methods Fifty patients with CHB were divided into two groups： group A of 25 ETV treatment naive patients treated with ETV 0.5 mg/d and group B of 25 LAM-resistance patients treated with ETV 1. 0 mg/d for 28 to 140 weeks. Antiviral responses were evaluated according to changes in serum HBV DNA （measured via real time polymerase chain reaction）. Sequence HBV DNA was performed if HBV DNA 〉4 logto copies/ml after 48 weeks to analyze the drugresistant mutation. Results In group A the HBV DNA was （7. 85 ± 0. 83）logto copies/ml, （3.24 ± 0.97） logto copies/ml, （2.96 ± 0.59） logto copies/ml, （ 2.86 ± 0.52） logto copies/ml and （ 2.70 ± 0） logto copies/ml at baseline and 12, 24, 48 and 96-week respectively; and In group B was （6.41 ± 1.43）logto copies/ml, （3.76±0.89） logto copies/ml, （2. 72 ± 0.09） logto copies/ml, （3. 14 ± 1. 22） log 10 copies/ml and （3. 04 ± 1. 06） logto copies/ml respectively. In group A, 64.0%, 80. 0%, 84.2% and 94.4% of the patients HBV DNA was reduced to the level under detection at 12, 24, 48 and 96-week respectively; and in group B, 32. 0%,68.0% ,80.0%,88.2% of the patients HBV DNA was reduced to the level under detection at 12,24,48 and 96-week respectively. ETV resistant （0 vs. 3） were detected in group A and B. Conclusion 48 and 96 weeks of ETV treatment resulted in significant virologic respond in the two groups. There were higher ETV-resistant rate in LAM-resistance patients.