曾有一项临床试验表明，单用聚乙二醇干扰素α-2a或联合拉米夫定治疗HBeAg阴性的慢性乙肝，停止治疗后24周的生化和病毒应答率显著高于单用拉米夫定。
意大利Bonino等报告，初始ALT和HBV-DNA水平、患者年龄、性别和HBV基因型显著影响聚乙二醇干扰素α-2a和（或）拉米夫定治疗后24周的联合应答率，HBV基因型可显著预测聚乙二醇干扰素α-2a联合或不联合拉米夫定治疗结束后1年的疗效。
该研究纳入518例HBeAg阴性乙肝患者，给予单用聚乙二醇干扰素α-2a、拉米夫定及二者联合治疗。对其疗效进行多因素分析，治疗后应答定义为ALT正常和HBV-DNA<2万拷贝/ml。
对所有治疗组进行分析的结果显示，应用聚乙二醇干扰素α-2a联合或不联合拉米夫定、年龄较轻、女性、起始ALT较高和起始DNA水平较低以及HBV基因型等因素可显著预测治疗结束24周后的联合应答。
在聚乙二醇干扰素α-2a或拉米夫定单药治疗组，基因B或C型患者较D型患者应答率高（P<0.001）。基因D型患者对聚乙二醇干扰素α-2a联合拉米夫定治疗的应答率高于聚乙二醇干扰素α-2a单药治疗（P=0.015）。
治疗结束1年后，意向治疗分析显示：单用聚乙二醇干扰素α-2a组、聚乙二醇干扰素α-2a联合拉米夫定治疗组、单用拉米夫定组的应答率分别为19.2%、19.0%和10%。基因B或C型患者聚乙二醇干扰素α-2a联合或不联合拉米夫定治疗的持续联合应答率均较高。
Gut. 2006 Nov 24; [Epub ahead of print]
Predicting response to peginterferon alfa-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B.
Bonino F, Marcellin P, Lau GK, Hadziyannis S, Jin R, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Brunetto M, Farci P, Popescu M, McCloud P.
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Italy.
Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Italy.
BACKGROUND AND AIMS: In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24-week post-treatment biochemical and virologic response rates with peginterferon alfa-2a +/- lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses has been investigated. PATIENTS AND METHODS: Multivariate analyses were performed using available data from 518 patients treated with peginterferon alfa-2a monotherapy +/- lamivudine, or lamivudine monotherapy. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA <20,000 copies/mL. RESULTS: In logistic regression analyses across all treatment arms, peginterferon alfa-2a (+/- lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response 24 weeks post-treatment. In the peginterferon alfa-2a and lamivudine monotherapy arms, patients infected with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to combination than peginterferon alfa-2a monotherapy (p=0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for peginterferon alfa-2a, 19.0% for combination, and 10.0% for lamivudine-treatment groups, with genotypes B or C associated with a sustained combined response to peginterferon alfa-2a +/-lamivudine therapy. CONCLUSIONS: Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response 24 weeks post-treatment, in patients treated with peginterferon alfa-2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon alfa-2a +/-lamivudine.
发表于 2007-2-10 03:02
