替比夫定和恩替卡韦治疗HBeAg阳性慢性乙型肝炎的疗效及HBeAg血清学转换的预测因素

Study on the efficacy and HBeAg seroconversion related factors of telbivudine and entecavir therapy in HBeAg positive chronic hepatitis B patients

目的观察替比夫定（LDT）与恩替卡韦（ETV）治疗HBeAg阳性慢性乙型肝炎的52周临床疗效。方法采用1：1随机单盲、对照设计。共入组HBeAg阳性慢性乙型肝炎患者180例，其中LDT组90例，LDT600mg口服，每天1次；ETV组90例，ETV0．5mg口服，每天1次。治疗52周进行疗效评估，并对HBeAg血清学转换相关的因素进行分析。根据资料不同采用t检验、x^2检验或Logistic回归分析进行统计学分析。结果治疗52周时，HBVDNA检测不到率，ETV组为88．9％，LDT组为78．9％，差异无统计学意义。HBeAg阴转率、HBeAg血清转换率和HBeAg较基线下降水平，LDT组分别为28．9％、27．8％和（774．7±542．4）PEIU／ml，ETV组分别为15．6％、14．4％和（603．4±480．5）PEIU／ml，两组比较，x^2值分别为4．63和4．80，t值为2．02，P值均〈0．05，差异有统计学意义。治疗52周时，病毒学突破率LDT组为4．4％，ETV组为0％，x^2=4．09，P〈0．05。LDT组和ETV组在治疗52周时是否出现HBeAg血清学转换与基线ALT和HBVDNA水平无相关性。多因素逐步Logistic回归分析显示，LDT组有3个因素与治疗52周HBeAg血清学转换相关，依次为：24周时HBeAg下降〉2log，12周时HBeAg下降〉1log，基线HBeAg水平；ETV组有3个因素与52周HBeAg血清学转换相关，依次为24周时HBeAg下降〉2log，36周时HBeAg下降〉2log，12周时HBeAg下降〉2log。结论治疗HBeAg阳性慢性乙型肝炎52周，LDT较ETV有更高的HBeAg转换率，ETV组有更低的耐药率。24周时HBeAg下降〉2log可同时作为两组患者52周HBeAg血清转换的最佳预测因素。

Objective To investigate the efficacy of Telbivudine and Entecavir for therapy of HBeAg positive chronic hepatitis B for 52 weeks. Methods In this random and control study, the efficacy of Telbivudine and Entecavir treatments were compared in 180 patients with HBeAg positive chronic hepatitis B.The patients were randomly assigned to a daily 600 mg Telbivudine treatment group or daily 0.5 mg Entecavir group for 52 weeks. Results At week 52, HBV DNA undetectable rate was better in the Entecavir-treated group than in the Telbivudine-treated group, but didn＇t reach statistical signficance. The viral break- through rates were significantly lower in the Entecavir-treated group than in the Telbivudine-treated group （ x^2 = 4.09, P 〈 0.05）. The clearance and seroconversion of HBeAg and the mean reductions of HBeAg from baseline at week 52 were significantly greater in the telbivudine-treated group than in the entecavirtreated group （ x^2 clearance 4.63, x^2seroconversion= 4.80, tmean reductions=2.02; P 〈 0.05）. The HBeAg seroconversion rates were not associated with both baseline ALT and baseline HBV DNA in both groups （P 〉 0.05）. In Telbivudine-treated group, the HBeAg decline〉2 log at week 24, HBeAg decline〉l log at week 12 and the HBeAg baseline were independent factors correlated to HBeAg seroconversion rates at week 52 by Binary Logistic analysis, and also in entecavir-treated group the HBeAg decline〉2 log at week 24, HBeAg decline 〉 2 log at week 36 and the HBeAg decline〉2 log at week 12 were independent factors correlated to HBeAg seroconversion rates at week 52. Conclusion Significant difference of HBeAg seroconversion rates at week 52 existed between Telbivudine-treated group and Entecavir-treated group. Entecavir is significantly superior to Telbivudine with less resistance to nucleosides. HBeAg decline〉2 log at week 24 is the best predicting factor for HBeAg seroconversion at week 52.