HBeAg阳性慢性乙型肝炎患者拉米夫定及其与普通干扰素序贯治疗效果比较

Lamivudine-interferon alpha 2b sequential therapy versus lamivudine monotherapy in HBeAg-positive chronic hepatitis B patients

目的比较拉米夫定一干扰素序贯治疗与拉米夫定单药治疗HBeAg阳性慢性乙型肝炎患者的疗效和安全性。方法选择172例HBeAg阳性慢性乙型肝炎患者，随机分为序贯治疗组83例和拉米夫定单药治疗组89例。序贯治疗组先用拉米夫定100mg／d治疗，从第25周开始加用干扰素a2b（5Mu，皮下注射，隔日1次），总疗程48周，停药后随访24周。单药治疗组单用拉米夫定100mg／d治疗，共48周，停药后随访24周。计量资料方差齐性用t检验，方差不齐用秩和检验，率的比较用X^2检验或Fisher确切概率法。结果序贯治疗组和单药治疗组的基线HBVDNA分别为（7．8±1．0）和（7．9±1．1）lg拷贝／mL（P〉0．05），基线ALT分别为（210．5±150．1）和（211．9±160．9）U／L（P〉0．05）。治疗结束时，序贯治疗组ALT为（78．4±146．1）U／L，单药治疗组ALT为（36．1±32．4）U／L，两组比较，差异有统计学意义（P〈0．05）；序贯治疗组HBVDNA为（4．5±1．5）lg拷贝／mL，单药治疗组HBVDNA为（3．8±1．3）lg拷贝／mL（P％0．05）；应答率分别为65．8％、83．5％（P％0．05）；HBeAg阴转率分别为31．6％、22．2％（P〉0．05）；血清学转换率分别为27．6％、16．0％（P〉O．05）。随访结束时，序贯治疗组ALT为（126．0±143．1）U／L，单药治疗组ALT为（82．7±83．0）U／L，两组比较，差异有统计学意义（p〈0．05）；序贯治疗组HBVDNA为（5．3±1．5）lg拷贝／mL，单药治疗组HBVDNA为（5．0±1．5）lg拷贝／mL，两组比较，差异无统计学意义（P〉0．05）；HBeAg阴转率分别为25．0％、32．3％（P〉0．05）；血清学转换率分别为25．0％、26．2％（P〉0．05）。治疗48周时YMDD耐药变异率序贯治疗组低于单药治疗组（10．5％比26．9％，P〈0．05）。结论拉米夫定一干扰素序贯治疗和拉米夫定单药治疗对HBeAg阳性慢性乙型肝炎患者疗效相似，但序贯治疗可减少病毒变异。

Objective To compare the efficacy and safety of lamivudine-interferon sequential therapy and lamivudine monotherapy in HBeAg-positive chronic hepatitis B （CHB） patients.Methods A total of 172 patients with HBeAg-positive CHB were randomized to sequential group （n= 83） or lamivudine group （n=89）. Sequential group were administrated with lamivudine 100 mg/d and 5 million units interferon alpha 2b subcutaneous injection every other day for 24 Weeks were added since week 25 of treatment. Lamivudine group were administrated with lamivudine 100 mg/d for 48 weeks. All subjects were followed up for 24 weeks after drug withdrawal. Measurement data with homogeneity of variance were analyzed by using t test and data with heterogeneity of variance were analyzed by using rank sum test. The comparison of rates was done by chi square test or Fisher exact test. Results The baseline hepatitis B virus （HBV） DNA levels of patients in sequential group and lamivudine group were （7.8±1.0） and （7.9 ± 1.1）lg copy/mL, respectively （P〉0.05）, and the baseline alanine aminotransferase （ALT） levels were （210. 5 ± 150. 1） and （211. 9 ± 160. 9） U/L, respectively （P〉0.05）. At the end of treatment, higher ALT levels [（78. 4± 146. 1） vs （36.±32.4） U/L, P〈0.05）] and HBV DNA levels [（4.5±1.5） vs （3.8±1.3） lg copy/mL, P〈0.05）] levels, lower response rates （65.8% vs 83.50%, P〈0.05）, and similar HBeAg loss rates （31.6% vs 22.2%, P〉0.05） and HBeAg seroconversion rates （27. 6% vs 16.0%, P〉0.05） were found in sequential group compared with lamivudine group. At the end of follow-up, higher ALT levels [（126.0±143.1） vs （82.7±83.0） U/L, P〈0.05）], similar HBV DNA levels [（5. 3±1. 5） vs （5.0±1. 5） lg copy/mL, P〉0.05）], similar HBeAg loss rates （25.0% vs 32.3%, P〉0.05） and HBeAg seroeonversion rates （25.0% vs 26.2%, P〉0.05） were found in sequential group compared with lamivudine group. YMDD motif mutation rate in sequential group was lower than lamivudine group at week 48 of treatment （10. 5 % vs 26. 9 %, P〈0.05）. Conclusions Lamivudine-interferon sequential therapy and lamivudine monotherapy are both effective in HBeAg-positive CHB patients, while HBV mutations are reduced in patients with sequential therapy.