National Institute for Infectious Diseases Prof. Dr. Matei Balş, Bucharest, Romania.
J Gastrointestin Liver Dis. 2009 Dec;18(4):425-31.
The study was designed to evaluate the efficacy and safety of peginterferon alpha-2a in HBeAg-positive chronic hepatitis B patients, nonresponders or relapsers after previous lamivudine or standard interferon therapy.
This prospective, national, multicentric, open label, not randomized trial enrolled 43 HBeAg-positive chronic hepatitis B patients with detectable HBsAg for at least 6 months prior to screening, positive HBeAg and negative anti-HBe, serum HBV DNA levels of at least 500,000 copies/mL by PCR assay, elevated ALT up to 10 x ULN, no response or relapse after previous lamivudine or standard interferon therapy. All eligible patients received pegIFN alpha-2a 180 micrograms weekly for 48 weeks with 24 weeks treatment free follow-up. There were two main efficacy assessments: HBeAg seroconversion and viral supression below 100,000 copies/mL.
HBeAg seroconversion rate at the end-of-treatment was 4.65% (n=2; p less than 0.05) increasing to 11.62% 24 weeks after end of therapy (n=5; p less than 0.05). The rate of viral supression at levels below 100,000 copies/mL was 23.25% (n=10; p less than 0.05) at end-of-treatment, and 16.3% (n=7; p less than 0.05) at end of follow-up. ALT normalization was obtained in 20.9% (p less than 0.05) of patients at end-of-treatment, the percentage being significantly higher - 37.2% (p less than 0.05) at the end of follow-up.
Even in a difficult-to-treat patient population with HBeAg-positive chronic hepatitis B, peginterferon alpha 2a proved to be efficient in a defined proportion of patients. The increase in HBeAg seroconversion rate from end-of-treatment (4.65%) to the end of follow-up period (11.62%) also proves the benefits of prolonged immunological effect of pegIFN alpha 2a.
本研究旨在评估聚乙二醇干扰素 α-2a 在 HBeAg 阳性慢性乙型肝炎患者中的疗效和安全性，这些患者在先前拉米夫定或标准干扰素治疗后无应答或复发。
这是一项前瞻性、全国性、多中心、开放性、非随机试验，纳入了 43 例 HBeAg 阳性慢性乙型肝炎患者，这些患者在筛选前至少有 6 个月可检测到 HBsAg，HBeAg 阳性且抗-HBe 阴性，PCR 检测血清 HBV DNA 水平至少为 500,000 拷贝/ml，ALT 升高至 10 x ULN，先前拉米夫定或标准干扰素治疗后无应答或复发。所有符合条件的患者每周接受 180μg 聚乙二醇干扰素 α-2a 治疗 48 周，随后进行 24 周的无治疗随访。主要疗效评估有两项：HBeAg 血清学转换和病毒载量低于 100,000 拷贝/ml。
治疗结束时的 HBeAg 血清学转换率为 4.65%（n=2；p 小于 0.05），治疗结束后 24 周时增加至 11.62%（n=5；p 小于 0.05）。治疗结束时病毒载量低于 100,000 拷贝/ml 的比例为 23.25%（n=10；p 小于 0.05），随访结束时为 16.3%（n=7；p 小于 0.05）。治疗结束时，20.9%（p 小于 0.05）的患者 ALT 恢复正常，随访结束时这一比例显著升高，为 37.2%（p 小于 0.05）。
即使在 HBeAg 阳性慢性乙型肝炎的难治性患者人群中，聚乙二醇干扰素 α-2a 也在一定比例的患者中显示出疗效。从治疗结束时（4.65%）到随访结束时（11.62%）的 HBeAg 血清学转换率增加也证明了聚乙二醇干扰素 α-2a 免疫作用持续时间延长的益处。
