序贯替比夫定156周治疗聚乙二醇干扰素α-2α经治未达到满意治疗终点HBeAg阳性慢性乙型肝炎的疗效观察

Clinical effect of 156-week telbivudine sequential therapy in HBeAg-positive chronic hepatitis B patients with suboptimal response to pegylated interferon-α-2α therapy

目的观察序贯替比夫定156周治疗聚乙二醇干扰素α-2α经治未达到满意治疗终点HBeAg阳性慢性乙型肝炎患者的疗效。方法35例经聚乙二醇干扰素α-2a治疗48周、HBVDNA〈500IU／ml且未出现HBeAg血清学转换的HBeAg阳性慢性乙型肝炎患者，序贯替比夫定（0．6g1次／d）治疗156周，观察HBeAg的阴转率和血清学转换率、HBVDNA阴转率及安全性、耐药率。并对该方案5年的疗效进行预测评价。对数据进行意向性分析（ITT）和符合方案分析（PP）。对计量资料采用t检验与秩和检验分析，对计数资料使用X2检验；对影响HBeAg血清学转换的预测因素采用多因素Cox回归分析。结果序贯替比夫定治疗能获得理想的HBeAg血清学转换率（ITT分析：85．71％；PP分析：87．88％），同时有良好的耐受性以及较低的耐药率。治疗期间，HBeAg阴转率和血清学转换率均随时间延长而上升，ITT分析显示24周HBeAg的阴转率和血清学转换率为48．57％、45．71％，156周HBeAg的阴转率和血清学转换率为94．29％和85．71％；PP分析显示24周HBeAg的阴转率和血清学转换率为45．45％、45．45％，156周HBeAg的阴转率和血清学转换率为93．94％和87．88％。治疗期间无一例患者出现病毒学突破。未出现HBsAg阴转病例。多因素Cox回归分析结果：ITT分析结果显示基线HBsAg水平（P=0．003，HR=0．445）、24周HBsAg较基线下降〉0．5 lgIU／ml（P=0．047，HR=0．436）可作为156周HBeAg血清学转换的预测因素；PP分析提示基线HBsAg水平（P=0．003，HR=0．404）、24周HBeAg较基线下降〉0．5lgCOI（P=0．048，HR=2．196）能作为156周HBeAg血清学转换的预测因素。该方案连续治疗5年可获得较好的疗效。结论聚乙二醇干扰素α-2α经治未达到满意治疗终点HBeAg阳性慢性乙型肝炎患者序贯替比夫定5年能获得较理想的疗效，可作为聚乙二醇干扰素α-2α经治未达到满意治疗终点HBeAg阳性慢性乙型肝炎患者挽救治疗的优选方案。

Objective To investigate the clinical effect of 156-week telbivudine sequential therapy in HBeAg-positive chronic hepatitis B patients with suboptimal response to pegylated interferon-α-2α （Peg-IFN- α-2α） therapy. Methods A total of 35 HBeAg-positive CHB patients with HBV DNA 〈 500 IU/ml who were treated with Peg-IFN-α-2α for 48 weeks and did not experience seroconversion of HBeAg were given telbivudine sequential therapy for 156 weeks. HBeAg clearance rate, HBeAg seroconversion rate, HBV DNA clearance rate, safety, and drug resistance rate were analyzed. The t-test was used for the analysis of continuous data and the chi-square test was used for the analysis of categorical data. A multivariate Cox regression analysis was used to identify the influencing factors for HBeAg seroconversion. Results Telbivudine sequential therapy achieved an ideal HBeAg seroconversion rate of 87.88% with good tolerability and low drug resistance. The HBeAg clearance rate and HBeAg seroconversion rate increased over the time of treatment and were 45.45% and 45.45%, respectively, at 24 weeks and 93.94% and 87.88%, respectively, at 156 weeks. No patient had virologic breakthrough or HBsAg clearance during treatment. The multivariate Cox regression analysis showed that baseline HBsAg level （hazard ratio [HR] = 0.404, P = 0.003） and 〉 0.5 lg IU/ml reduction in HBeAg at 24 weeks （HR = 2.196, P = 0.048） were predictive factors for HBeAg seroconversion at 156 weeks. Conclusions In HBeAg-positive CHB patients with suboptimal response to Peg-IFN-α-2α therapy, 156- week telbivudine sequential therapy has a good clinical effect and can be used as an optimal regimen for such patients.