阿德福韦酯治疗e抗原阳性慢性乙型肝炎的疗效预测指标探讨

The predictive value of ALT, HBeAg and HBV DNA levels at baseline and the degree of HBV suppression at week 12 adefovir dipivoxil treatment to the efficacy of it at week 52 in patients with HBeAgpositive chronic hepatitis B

目的评价HBeAg阳性慢性乙型肝炎患者治疗前ALT、HBeAg、HBVDNA水平以及治疗12周时HBV抑制程度对阿德福韦酯（ADV）治疗52周患者疗效的预测价值。方法98例HBeAg阳性成年慢性乙型肝炎患者进入研究。筛选时血浆HBVDNA定量≥1×10^6拷贝／ml，血清ALT水平1．5～10倍正常值上限（ULN）。患者接受ADV10mg／d，共52周治疗。定期随访，检测血清HBV标志物及HBVDNA。比较不同基线ALT、HBeAg、HBVDNA水平以及治疗12周时不同血清HBVDNA水平患者治疗52周时的疗效差异。结果ADV治疗52周时，血清HBVDNA〈10^3拷贝／ml的患者，基线ALT〉5×ULN者（72．7％）高于ALT〈2×ULN者（38．0％），P〈0．05；基线HBeAg≤350s／co者（66、7％）高于HBeAg〉350s／co者（30．2％），P〈0．01；基线HBVDNA≤108拷贝／ml者（53．0%）高于血清HBVDNA〉10^8拷贝／ml者（34．4％），P〈0．05。52周HBeAg血清学转换率在基线HBeAg水平≤350s／co者和HBeAg〉350s／co者分别为42．2％和7．5％（P〈0．01）。治疗12周时血清HBVDNA〈10^3拷贝／ml、10k10^5拷贝／ml和〉10^5拷贝／ml组患者，52周时血清HBVDNA〈10^3拷贝／ml的比例分别为82．6％、57．1％和17．5％，组间差异均有统计学意义（P值均〈0．05）；3组患者HBeAg血清学转换率分别为52．2%、25．7％和5．0％，组间差异均有统计学意义（P值均〈0．05）；3组患者52周ALT复常率分别为100％、83％和75％，血清HBVDNA〈10^5拷贝／ml组高于〉10^5拷贝／ml组（P〈0．05）。相关分析显示，治疗52周时的血清HBVDNA水平及HBeAg血清转换与治疗12周时血清HBVDNA水平中度相关（P〈0．01）。结论HBeAg阳性慢性乙型肝炎患者ADV治疗12周时血清HBVDNA水平对治疗52周的疗效的预测价值优于基线指标，治疗12周时血清HBVDNA〈10，拷贝／ml者，52周时能达到更佳的疗效。

Objective To study the predictive value of ALT, HBeAg and HBV DNA levels at baseline and HBV DNA levels at week 12 adefovir dipivoxil （ADV） treatment to the efficacy of it at week 52 in patients with HBeAg-positive chronic hepatitis B （CHB）. Methods Ninety-eight HBeAg-positive CHB patients with serum HBV DNA ≥ 1 × 10^6 copies/ml and ALT levels between 1.5 to 10 times of upper limits of normal （ULN） were enrolled in the study. Ten mg/d of ADV was administered for 52 weeks. Line serum samples were collected for measuring HBV DNA and HBV markers. The efficacy of the treatment at week 52 was evaluated in patients with different ALT, HBeAg and HBV DNA levels at baseline and HBV DNA levels at week 12 after treatment. Results At week 52 of ADV treatment, the rates ofHBV DNA〈103 were 72.7%, 66.7% and 53.0% respectively in patients with ALT 〉 5 x ULN, HBeAg ≤350 s/co and HBV DNA ≤10^8 copies/ml. Significant differences were found between them and patients with ALT 〈 2 × ULN （38.0%, P 〈 0.05）, HBeAg 〉350 s/co （30.2%, P 〈 0.01） and HBV DNA 〉10^5 copies/ml （34.4%, P 〈 0.05） at baseline. HBeAg seroconversion rates were 42.2% and 7.5% （P 〈 0.01） in patients with HBeAg titer ≤ 350 and 〉350 S/co at baseline. In patients with HBV DNA 〈10^3, 10^3-10^5 and 〉10^5 copies/ml at week 12, the ratios of them with HBV DNA 〈10^3 copies/ml at week 52 were 82.6%, 57.1% and 17.5% and significant differences were found between these groups （P 〈 0.05）; HBeAg seroconversion rates were 52.2%, 25.7% and 5.0% （P 〈 0.05）; ALT normalization rates were 100%, 83% and 75%, significantly higher in patients with HBV DNA 〈103 copies/ml than those with HBV DNA〉10^5 copies/ml （ P 〈 0.05） at week 12. HBV DNA and HBeAg seroconversion at week 52 correlated with HBV DNA levels at week 12 （r = 0,6 and r = 0.5 respectively, P 〈 0.01）. Conclusions InHBeAg-positive CHB patients treated with adefovir dipivoxil, HBV DNA levels at week 12 can be used to predict the efficacy at week 52. HBV DNA〈10^3 copies/ml at week 12 predict a better treatment result at week 52.