干扰素治疗慢性乙型肝炎时e抗原血清学转换的相关因素

目的探讨HBeAg阳性慢性乙型肝炎在聚乙二醇干扰素α-2a（PEG-IFN α-2a）治疗过程中HBeAg血清学转换和病毒学应答的相关因素，HBeAg血清学转换与HBV DNA应答的相关性。方法患者采用PEG-IFNα-2a每次180μg，皮下注射，每周1次，共治疗48周，治疗结束后随访24周。用Abbott公司生产的第三代HBV血清学检测试剂和AXSYM自动酶标检测仪检测血清HBeAg、抗-HBe，实时荧光定量PCR检测HBVDNA载量，分析不同治疗阶段和随访结束的病毒学应答率（HBV DNA〈1．0×10^5拷贝／ml），HBeAg血清转换率及变化规律和影响病毒学应答和HBeAg血清转换的因素。结果治疗12周和随访结束时HBeAg血清转换组和非转换组的ALT水平比较，差异有统计学意义。病毒学应答无论在治疗期还是随访结束时，应答组与非应答组之间的ALT水平差异均有统计学意义。HBeAg血清学转换与非转换组之间的HBV DNA载量之间在治疗12周、治疗结束和随访结束时，差异无统计学意义。治疗期间病毒学应答与非应答组的HBV DNA载量之间的差异有统计学意义，但持续病毒学应答与HBV DNA载量无显著相关性。治疗12、24周和48周获得病毒学应答组的HBeAg血清转换率分别为43．8％、21．4％和18．9％。治疗12、24周和48周时病毒学应答组，在随访结束时的HBeAg的血清转换率分别为42．9％、33．3％和27．6％。多因素分析显示，治疗72周的HBeAg血清转换与治疗结束时的HBV DNA阴转显著相关（OR=2．15，95．0％CI=1．744-2．664，P〈0．01）。结论治疗12周和持续HBeAg血清学转换以及病毒学应答均与ALT基线水平相关，HBeAg血清学转换与基础HBV DNA载量无关，但与治疗过程中病毒学应答相关。

Factors associated with HBeAg seroconversion in chronic hepatitis B patients treated with interferon alfa-2a

OBJECTIVE: The aim of this paper was to investigate the factors associated with viral response and HBeAg seroconversion and the relationship between them at different stages of interferon treatment in HBeAg-positive chronic hepatitis B patients. METHODS: PEG-IFN alfa-2a was injected subcutaneously in doses of 180 microg once a week for 48 weeks to HBeAg-positive chronic hepatitis B patients, and the patients were followed for another 24 weeks after the treatment. The serum HBV DNA load was measured by real-time quantitative PCR assay. Microparticle enzyme immunoassay analysis (MEIA) was then carried out by an automatic enzyme immunoassay analysis instrument to measure HBeAg and anti-HBe. Virological response and HBeAg seroconversion rates, and the factors associated with them were analyzed. RESULTS: The differences in ALT baselines between viral responding and non-responding groups were significant at treatment time and at the end of the follow-up period. These differences were also significant in patients with HBeAg seroconversion at 12 weeks and at the end of the follow-up period compared with the non-conversion group. No significant difference of HBV DNA baseline was observed between the HBeAg seroconversion and non-conversion group. At 12, 24 and 48 weeks, in patients with viral response during the treatment, their HBeAg seroconversion rates were 43.8%, 21.4% and 18.9% respectively; their respective HBeAg seroconversion rates remaining at 72 weeks were 42.9%, 33.3% and 27.6%. HBeAg seroconversion was related to HBV DNA negativity at 48 weeks treatment in the multivariate analysis (OR=2.15, 95.0% CI=1.744-2.664, P less than 0.01). CONCLUSIONS: Viral response and early and sustained HBeAg seroconversion were associated with pretreatment ALT levels. HBeAg seroconversion was related to viral response during IFN treatment, but not to the baseline HBV DNA load.