聚乙二醇化干扰素仪α-2a治疗慢性乙型肝炎的疗效及影响因素

Responses of peginterferon-alpha 2a antiviral therapy in chronic hepatitis B patients

目的 观察聚乙二醇化干扰素（PEG-IFN） α-2a治疗慢性乙型肝炎患者抗病毒的疗效及影响抗病毒疗效的因素。方法 将102例ALT〉2×正常值上限（ULN）的慢性乙型肝炎患者分成HBeAg阳性和HBeAg阴性两组，用PEG-IFN α-2a 180μg皮下注射，每周1次治疗，患者基本疗程12个月，6个月无治疗应答者停药。观察治疗结束时及治疗结束后6、12、18、24、30个月应答情况。观察ALT水平，HBVDNA载量及肝组织炎症和纤维化程度对治疗应答的影响。结果（1）HBeAg阳性组患者治疗结束时的完全应答率及停药后6、12、18、24、30个月的完全应答率与HBeAg阴性组患者相似，差异均无统计学意义。（2）HBeAg阳性组患者治疗前ALT〉3×ULN者治疗结束时的完全应答率为78．8％，2×ULN〈ALT≤3×ULN患者完全应答率为52．2％，差异有统计学意义（X^2=4．40，P〈0．05），而HBeAg阴性组患者，差异无统计学意义。（3）治疗前HBV DNA载量水平（低、中、高3个组），HBeAg阳性和HBeAg阴性组患者治疗结束时的完全应答率，差异均无统计学意义。（4）HBeAg阳性组患者治疗前肝组织炎症G3、G4组完全应答率为85．7％，G1、G2组患者完全应答率为55．9％，差异有统计学意义（X^2=4．19，P〈0．05），而HBeAg阴性组患者分别为81．8％和79．2％，差异无统计学意义。HBeAg阳性和HBeAg阴性组患者肝纤维化程度S1、S2组与S3、S4组的治疗完全应答率比较，差异均无统计学意义。结论 PEG-IFN α-2a对HBeAg阳性和HBeAg阴性的慢性乙型肝炎患者均有较好的治疗应答。对肝组织炎症活动度高（G3、G4）和血清ALT高水平（〉3×ULN）的患者，PEG-IFN α-2a治疗的疗效好。

Objective To study the responses of peginterferon-alpha 2a antiviral therapy in chronic hepatitis B （CHB） patients. Methods One hundred two CHB patients with their serum ALT values higher than 2 × the upper limit of the normal （ULN） were divided into a HBeAg-positive and a HBeAg -negative group. All patients were treated with peginterferon-alpha 2a by subcutaneous injection （180 microgram once weekly）. After treatment for 6 months, patients without a defined therapeutic response were dropped from the treatment group; the others completed a 12 month therapy. The sustained response and the antiviral effect of the treatment were assessed at the end of the therapy. To investigate the possible impact factors of the response to peginterferon-alpha 2a, we studied the therapeutic response of patients with different serum ALT levels, inflammation grades of liver histology, stages of fibrosis, and HBV viral load levels. Results （1） There was no statistical difference of the rates of response at the end of treatment and 6, 12, 18, 24 and 30 months after the cessation of therapy between the HBeAg-positive and the HBeAg-negative groups. （2） In the HBeAg- positive group, the rates of response of patients with serum ALT values 〉3 × ULN were significantly higher than those with serum ALT values ≤ 3 × ULN （X^2 = 4.40, P 〈 0.05）. However, no statistical difference of serum ALT levels was found in the HBeAg-negative group. （3） In both HBeAg-positive and HBeAg-negative groups, no difference was revealed in the rates of response among patients with different levels of HBV viral loads. （4） In the HBeAg-positive group, patients with more severe liver inflammation histologically （G3 and G4） had significantly higher response rates than those with milder inflammation （G1 and G2） （ X^2 = 4.19, P 〈 0.05）, but no similar statistical differences were found in the HBeAg-negative group. Moreover, there was no difference in the rates of response among patients in different stages of liver fibrosis in both HBeAg- positive and HBeAg-negative groups. Conclusions Similar rates of response and sustained virological response to the peginterferon-alpha 2a treatment can be achieved in both HBeAg-positive and HBeAg-nega- tive patients. Hepatic fibrosis is not a predictor of poor therapeutic response. For HBeAg-positive patients, more severe liver inflammation identified with liver biopsies （G3 or G4） and high serum ALT values （〉 3 × ULN） can be considered as predictors of a good therapeutic response.