恩替卡韦或其联合阿德福韦酯补救治疗拉米夫定联合阿德福韦酯应答不佳的慢性乙型肝炎

Entecavir 1.Omg monotherapy or entecavir plus adefovir dipivoxil for patients with lamivudine-resistant chronic hepatitis B had suboptimal response to lamivudine plus adefovir dipivoxil

目的对拉米夫定（LAM）初治耐药后，LAM联合阿德福韦酯（ADV）应答不佳的慢性乙型肝炎患者，分别采用恩替卡韦（ETV）单药或ETV联合ADV进行补救治疗，比较两种补救方案的疗效。方法对LAM初治耐药后应用LAM联合ADV应答不佳的40例患者，分别应用ETV1．0mg／d（14例）及ETV0．5mg／d联合ADV10mg／d（26例）两种方案进行补救治疗，至少观察48周，定期监测HBVDNA、肝肾功能、HBV标志物等指标。根据资料不同分别采用t检验Wilcoxon检验或，检验。结果两组患者采用补救治疗前的基线情况差异无统计学意义。分别采用两种补救方案治疗后，两组患者HBVDNA水平均有下降，但ETV联合ADV组下降幅度较大。补救治疗24周时，ETV1．0mg组有28．6％（4例）达到HBVDNA转阴，ETV联合ADV组则有80．8％（21例）达到HBVDNA转阴，χ2 =8．469，P=0．004，差异具有统计学意义；48周时，ETV1．0mg组仍仅有4例患者HBVDNA转阴，而ETV联合ADV组全部26例患者均达到HBVDNA转阴。补救治疗24周时，ETV1．0mg组有42．9％（6例）患者ALT复常，ETV联合ADV组有92．3％（24例）患者ALT复常，χ2 =9．337，P=0．002，差异具有统计学意义；48周时，ETV1．0mg组有57．1％（8例）患者ALT复常，而ETV联合ADV组所有患者均达到ALT复常。补救治疗48周时，ETV1．0mg组有1例患者发生HBeAg血清学转换，ETV联合ADV组有4例患者发生HBeAg血清学转换。结论对于LAM耐药后LAM联合ADV应答不佳的慢性乙型肝炎患者，采用ETV联合ADV的补救方案较ETV单药1．0mg的方案更为有效，可以实现更好的病毒学及生物化学应答。

Objective To evaluate the efficacy of entecavir （ETV） 1.0 mg/d or ETV plus adefovir dipivoxil （ADV） in adults with chronic hepatitis B virus （HBV） infection who had previously resisted lamivudine （LAM） and failed with rescue treatment of LAM ＋ ADV. Methods 40 patients were enrolled. 14 patients were treated with ETV 1.0 mg/d monotherapy while 26 patients were treated with ETV 1.0 mg/d ＋ ADV 10 mg/d. The HBV DNA level, liver function, HBV serology and renal function were observed. ResultsThere was no statistically significant difference with baseline situation between group ETV 1.0 mg and group ETV ＋ ADV. HBV DNA level in group ETV 1.0 mg was （5.768 ±0.709） logl0 copies/ml on baseline, and it declined to （4.712 ± 0.846） logl0 copies/ml, （3.914 ±0.996） logl0 copies/ml, （3.702 ± 0.934） logl0 copies/ml, （3.879 ±0.913） logl0 copies/ml and （3.855 ±1.070） log10 copies/ml at 4, 8, 12, 24 and 48 weeks. HBV DNA level in group ETV ＋ADV was （5.703 ±0.845） logl0 copies/ml on baseline, and it declined to （4.476 ±0.905） logl0 copies/ml, （3.590 ±0.884） logl0 copies/ml, （2.987 ±0.673） logl0 copies/ml and （2.933 ± 0.535） logl0 copies/mt at 4, 8, 12 and 24 weeks. At 24 weeks, there were 28.6% patients achieved HBV DNA 〈 500 copies/ ml in group ETV 1.0 mg, but there were 80.8% patients in group ETV ＋ ADV achieved this level. Statistically significant difference existed between （χ2 = 8.469, P = 0.004 ）. At 48 weeks, there were still 4 patients achieved HBV DNA 〈 500 copies/ml in group ETV 1.0 mg, but patients in group ETV ＋ ADV all achieved it. At 24 weeks, ALT levels of 42.9% patients in group ETV 1.0 mg were back to normal, but there were 92.3% patients＇ ALT levels back to normal in group ETV ＋ ADV. There was statistically significant difference （ χ2 = 9.337, P = 0.002）. At 48 weeks, ALT levels of 57.1% patients in group ETV 1.0 mg were back to normal, but all patients＇ ALT levels were back to normal in group ETV ＋ ADV. At 48 weeks, there was 1 patient with HBeAg seroconversion in group ETV 1.0 mg while there were 4 patients in group ETV ＋ ADV. Conclusion As rescue treatment for patients with chronic hepatitis B who had previously resisted LAM and failed with treatment of LAM＋ADV, ETV＋ADV was more efficient than ETV 1.0 mg monotherapy, and it can achieve better virological and biochemical response.