干扰素α与阿德福韦酯不同联合方法治疗HBeAg阳性慢性乙型肝炎的疗效

目的 观察IFNα联合阿德福韦酯(ADV)治疗HBeAg阳性慢性乙型肝炎(CHB)的临床疗效,探讨理想的联合治疗方案.方法 2005年1月至2009年6月纳入河北医科大学第三医院HBeAg阳性CHB患者156例.56例患者HBV DNA≥1×107拷贝/mL、或纤维化分期≥S3、或既往单药治疗失败(复发)者,予以初始IFNα联合ADV治疗;52例未达上述指标患者接受初始IFNα单药治疗.24周时依据患者HBV DNA、HBeAg、HBsAg变化调整治疗方案:16例取得早期应答的初始IFNα联合ADV治疗组患者调整为IFNα单药维持治疗,其余患者与初始IFNα单药治疗组未达到早期应答者共同接受IFNα联合ADV治疗.另选48例作为标准治疗组,接受全程IFNα单药治疗.48周时复评全部患者HBV DNA、HBeAg、HBsAg定量,并决定是否延长疗程.最终于72周评估患者疗效、安全性、耐药复发等,数据行卡方检验.结果 治疗24周,初始IFNα联合ADV治疗组早期应答率达28.6%,其中HBV DNA阴转率、ALT复常率(53.6%,62.5%)与初始IFNα单药治疗组(32.7%,x2=4.78;40.4%,x2=5.21)、标准治疗组(27.1%,x2=5.28;37.5%,x2=6.46)比较,差异均有统计学意义(均P<0.05),且HBeAg阴转率较标准治疗组更高(39.3%比18.8%,x2=7.48,P<0.05).48周时,初始IFNα联合ADV治疗组16例取得早期应答者停用ADV后,5例HBeAg复阳,3例病毒学反弹;HBV DNA阴转率为73.2%,HBeAg转换率为41.1%,HBsAg清除率为12.5%.其中96例接受不同联合方法治疗的患者HBV DNA阴转率、HBeAg转换率、HBsAg清除率分别为65.6%、33.3%和8.3%.72周时不同联合方法治疗组患者整体复发率与标准治疗组相当,HBsAg清除率上升2.7%.结论 IFNa联合ADV抗病毒治疗对提高应答率优势明显.结合患者基线特征、治疗反应,制订不同联合方案,不失为当前CHB抗病毒优化治疗理想策略之一.

Abstract：

Objective To investigate the efficacy of interferon α(IFNα)and adefovir dipivoxil (ADV)combination therapy in HBeAg positive chronic hepatitis B(CHB)patients and to explore the optimized strategy for individualized treatment.Methods A total of 156 HBeAg positive CHB patients were enrolled in the study from January 2005 to June 2009 in the Third Affiliated Hospital of Hebei Medical University.Fifty-six CHB patients with hepatitis B virus(HBV)DNA≥1 X 107copy/mLand/or liver fibrosis stage≥S3,or previous monotherapy failure(relapse)were treated with initial IFNα and ADV combination therapy.Fifty-two patients who didn't meet any of the above baseline characteristics received initial IFNα monotherapy.The remaining 48 patients treated with IFNα monotherapy for full treatment duration were considered as control.At week 24 of treatment,the treatment regimens were adjusted according to quantitative changes of HBV DNA,HBeAg and HBsAg:16 patients who achieved early response in group of initial IFNα and ADV combination therapy subsequently received IFNα monotherapy,the other patients in group of initial combination therapy together with patients who did not achieved early response in group of initial IFNα monotherapy subsequently received IFNα and ADV combination treatment.The HBV DNA levels,HBeAg and HBsAg titers were detected at the end of 48 weeks of treatment to determine the treatment duration.The treatment efficacy,safety,drug resistance and relapse rates were finally evaluated at week 72.All data were analyzed using chi square test.Results At week 24,the early response rate in group of initial combination therapy was 28.6%,and the HBV DNA negative rate and alanine aminotransferase(ALT)normalization rate were significantly higher than those in groups of initial IFNα monotherapy and control(53.6%vs 32.7%vs 27.1%and 62.5%vs 40.4%vs 37.5%,respectively,P<0.05);in addition,HBeAg loss rate was higher than control group(39.3%vs 18.8%,x2=7.48;P<0.05).At week 48,five of 16 patients who achieved early response developed HBeAg reversion and three cases accompanied with virological breakthrough in group of initial combination therapy after switching to IFNα monotherapy,while the rates of HBV DNA negative,HBeAg seroconversion and HBsAg clearance were 73.2%,41.1%and 12.5%,respectively.The HBV DNA negative rate,HBeAg seroconversion rate and HBsAg clearance rate in 96 patients Who had received different combination treatment regimens were 65.6%,33.3%and 8.3%,respectively.At week 72,the relapse rate in individualized treatment group was comparable to those in control group,while HBsAg clearance rate increased 2.7%in individualized treatment group.Conclusions IFNα and ADV combination treatment could improve early biochemical and virological responses.Individualized treatment strategy based on baseline characteristics and treatment responses may be helpful for optimizing antiviral treatment in CHB patients.