拉米夫定治疗e抗原阴性慢性乙型肝炎的早期预测指标分析

目的 评价拉米夫定(LAM)治疗e抗原阴性慢性乙型肝炎患者治疗前基线ALT、HBsAg、HBV DNA水平以及治疗4周和12周时HBV DNA<1×10~3拷贝/ml对其治疗104周时抗HBV疗效的预测价值. 方法 127例成年e抗原阴性慢性乙型肝炎患者均接受LAM 100 mg/d治疗,且均完成≥104周的治疗.治疗期间定期复查肝功能、HBV标志物(HBsAg、抗-HBs,HBeAg、抗-HBe、抗-HBc)及HBV DNA水平.分别比较和分析不同基线ALT、HBsAg、HBV DNA水平及治疗4周和12周时不同HBV DNA水平与治疗104周时疗效的关系.数据采用x~2检验及多元逐步Logistic回归分析.结果 基线ALT<5×正常值上限(ULN)和ALT≥5×ULN两组患者,治疗104周血清HBV DNA<1×10~3拷贝/ml的比例分别为50.0%和86.8%(P<0.01).基线HBsAg<2000 COI和HBsAg≥2000 COI两组患者,治疗104周时HBsAg<500 COI的比例分别为19.1%和17.5%(P>0.05);HBsAg/抗-HBS血清学转换率分别为2.1%和2.5%(P>0.05),血清HBV DNA<1×10~3拷贝/ml的比例分别为61.7%和67.5%(P>0.05).基线HBV DNA<1×10~6拷贝/ml和HBV DNA≥1×10~6拷贝/ml两组患者,至治疗4周和12周时HBV DNA<1×10~3拷贝/ml的比例差异均有统计学意义(P值均<0.01),但至治疗104周时HBV DNA<1×10~3拷贝/ml的比例分别为62.7%和67.1%,差异无统计学意义(P>0.05).治疗4周时HBVDNA<1×10~3拷贝/ml和HBV DNA≥1×10~3拷贝/ml两组患者,104周时HBV DNA<1×10~3拷贝/ml的比例分别为70.7%和60.9%(P>0.05);治疗12周时HBV DNA<1×10~3拷贝/ml和HBV DNA≥1×10~3拷贝/ml两组患者,104周时HBV DNA<1×10~3拷贝/ml的比例分别为78.8%和38.1%(P<0.01).结论 基线ALT≥5×ULN和治疗12周HBV DNA<1×10~3拷贝/ml的e抗原阴性慢性乙型肝炎患者用LAM继续治疗至104周时可以取得较好的病毒学应答.治疗前不同基线HBsAg水平对治疗104周时HBsAg的水平、HBsAg/抗-HBs血清学转换率和HBV载量的预测价值不大;基线HBV DNA水平对104周时是否获得病毒学应答的预测价值也不大.

Early prediction of lamivudine response in e antigen-negative chronic hepatitis B patients

Objective To evaluate the effects of ALT, HBsAg and HBV DNA at the baseline, 4and 12 weeks after lamivudine treatment on the long term (104 weeks) response in e antigen-negative chronic hepatitis B patients. Methods 127 adult e antigen-negative chronic hepatitis B patients were enrolled in this study. All patients received treatment on LAM 100 mg/d for at least 104 weeks. The liver function, serum HBV markers and HBV viral load were regularly checked during the treatment. The effects of ALT, HBsAg and HBV DNA at the baseline, 4 and 12 weeks after lamivudine treatment on the response at 104 weeks were statitistically analyzed. Results The proportion of patients with serum HBV DNA <10~3 copies / ml at 104 weeks after LAM treatment was 50.0% and 86.8% in patients with baseline ALT< 5 ULN and ALT≥5 ULN, respectively (P<0.01). In patients with baseline HBsAg <2000 COI and HBsAg≥2000 COI, the propor-tion of patients with serum HBsAg < 500 COI at 104 weeks after LAM treatment was 19.1% and 17.5%, respectively (P>0.05). The HBsAg serological conversion rates were respectively 2.1% and 2.5%, respec-tively (P>0.05), the proportion of patients with serum HBV DNA <1×10~3 copies/ml was 61.7% and 67.5%, respectively (P>0.05). In patients with baseline HBV DNA <10~6 copies/ml and HBV DNA≥1×10~6 copies/ml, the proportion of patients with HBV DNA<103 copies/ml were statistically different at 4 weeks and 12 weeks after treatment, however, the proportion of patients with HBV DNA <1×10~3 copies/nil at 104 weeks after LAM treatment was 62.7% and 67.1%, respectively (P>0.05). In patients with HBV DNA <1× 10~3 copies/nil and HBV DNA≥1×10~3 copies/ml at 4 weeks after treatment, the proportion of patients with HBV DNA <1×10~3 copies/ml at 104 weeks after LAM treatment was 70.7% and 60.9%, respectively (P> 0.05). In patients with HBV DNA <10~3 copies/nil and HBV DNA≥1×10~3 copies/ml at 12 weeks after treatment, the proportion of patients with HBV DNA <10~3 copies/ml at 104 weeks after treatment was 78.8% and 38.1%, respectively (P<0.01). Conclusion e antigen negative chronic hepatitis B patients with baseline ALT ≥ 5 ULN and HBV DNA <1×10~3 copies/ml at 12 weeks after treatment have better virological response at 104 weeks after LAM treatment. The baseline HBsAg and HBV DNA load are associated with the virological response at 104 weeks after LAM treatment.