干扰素α个体化治疗HBeAg阴性慢性乙型肝炎2年随访

Long-term efficacy of individualized interferon-alpha therapy for HBeAg-negative chronic hepatitis B patients： a 2-year follow-up study

目的了解IFN-α个体化治疗HBeAg阴性慢性乙型肝炎（CHB）患者的疗效。方法经肝组织穿刺活检证实的HBeAg阴性CHB患者76例，给予IFN-α1b治疗，每次5MU，每周3次。治疗结束后随访至少24个月。联合应答定义为血清ALT复常，且HBV DNA〈3log10拷贝／mL。所有资料均行意向性分析（ITT）。结果脱落6例。疗程中位数为8.5（2-24）个月，终点疗程中位数为6.0（2-19）个月，终点疗程第75百分位数为10.0个月。治疗末时联合应答率为46.1％（35／76），随访12个月时为43．3％（33／76），随访24个月时为40．8％（31／76）。随访12个月时复发率为20．0％（7／35），随访24个月时为25．7％（9／35）。多变量二分类Logistic分析显示，肝组织炎性活动度较高者较易应答（偏回归系数=0.834，P=0.023，OR=2.303，95％可信区间为：1.120，4.735），而性别、年龄、肝组织纤维化程度、ALT、AST、HBV DNA载量等为非疗效影响因素。结论IFN-α个体化治疗HBeAg阴性CHB患者有一定的持续效应。

Objective To investigate the efficacy of individualized interferon （IFN）-alpha therapy in HBeAg-negative chronic hepatitis B＂ patients. Methods Seventy-six Chinese HBeAg-negative chronic hepatitis B patients proven by liver biopsy were treated with 5 MU recombinant IFN-alpha 1b subcutaneously thrice every week. All the patients were followed up for at least 24 months the combined responses were defined as normalization of serum alanine transaminase （ALT） and HBV DNA 〈 3 log10 copy/mL. An intention-to-treat （ITT） analysis was used in this paper in which all 76 patients were included. Results Six patients were lost. Treatment duration was in the range 2-24 months with a median of 8.5 months, and combined responses were achieved at a median of 6.0 months （range 2-19 months） of treatment duration. Seventy-five-percentile of treatment duration to endpoints was 10.0 months. The combined response rate was 46.1% （35/76） at the end of treatment, 43.3%0 （33/76） at 12-month follow-up and 40. 8% （31/76） at 24- month follow-up. The relapse rate was 20. 0% （7/35） and 25.7%（9/35） at 12-month and 24-month follow-up, respectively. Higher necroinflammatory activity in liver biopsy predicted a good response, while gender, age, liver fibrosis, baseline ALT, aspartate aminotransferase levels and baseline HBV DNA levels were not impact factors of therapeutic effects by binary Logistic regression analysis. Conclusion Individualized prolonged IFN-alpha regimen lead to considerable sustained disease suppression in patients with HBeAg-negative chronic hepatitis B.