阿德福韦酯治疗e抗原阳性慢性乙型肝炎的疗效预测因素研究

Predictors of response in patients with HBeAg-positive chronic hepatitis B with adefovir dipivoxil treatment

目的探讨阿德福韦酯治疗HBeAg(+)慢性乙型肝炎的疗效预测指标,为个体化治疗提供依据。方法于2004年10月至2005年12月在北京大学第一医院等5所医院进行该研究,选取连续应用阿德福韦酯治疗48周的HBeAg(+)慢性乙型肝炎患者共140例,采用Logistic回归分析阿德福韦酯治疗48周的疗效预测指标。结果基线血清丙氨酸转氨酶(ALT)、HBV DNA水平和24周时HBV DNA阴转为48周HBV DNA阴转的预测指标;研究中基线ALT≥134.5U/L、HBV DNA≤6.57lg拷贝/mL和24周HBV DNA阴转者治疗至48周时的HBV DNA阴转率(93.3%)、HBeAg阴转率(60%)、HBeAg血清转换率(40%)均较高。治疗24周时HBV DNA未阴转者继续治疗至48周时仍有47.8%的患者发生HBV DNA阴转、8.6%的患者发生HBeAg血清转换。结论慢性乙型肝炎患者应用阿德福韦酯治疗前HBV DNA低水平、ALT高水平且24周时HBV DNA阴转是48周疗效较好的预测指标;治疗24周时HBV DNA未阴转者不应放弃治疗。

Objective To investigate the effective predictors of response in HBeAg-positive patients treated with adefovir dipivoxil（ADV） and to provide evidence for individualized treatment. Methods Patients administered with ADV for 48 weeks in a randomized, placebo-controlled, multicenter trial were studied. Statistical analyses, such as Backward stepwise logistic regression and 2 × 2 method were used for predictors analysis at week 48. Results The baseline serum ALT levels, HBV DNA levels, and undetectable serum HBV DNA by PCR at week 24 were predictors for HBV DNA negativity at week 48. The median of serum ALT levels and HBV DNA levels prior to treatment were 134. 5 U/L and 6. 57 lg copies/ mL,respectively. Patients with baseline ALT levels higher than the median, HBV DNA levels lower than the median, and serum HBV DNA undectectable by PCR at week 24 had greater rate of HBV DNA negativity （93.3%）, HBeAg loss （60%）and HBeAg seroconversion（40% ） at week 48 than the others. 47. 8% of patients whose HBV DNA levels were positive at week 24 also achieved HBV DNA negativity at week 48, and 8. 6% achieved HBeAg seroconversion. Conclusion Better response at week 48 has significantly higher serum ALT levels and lower HBV DNA levels prior to treatment and HBV DNA negativity at week 24 compared with non-response. Patients whose HBV DNA levels ware still positive at week 24 should continue therapy.