Relapse of hepatitis B e antigen-positive patients after standardized interferon α regimen: A five-year follow-up study
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摘要: 目的 评价α-干扰素(interferon-alpha,IFN-α)治疗乙肝e抗原(hepatitis B e antigen,HBeAg)阳性慢性乙型肝炎患者5年随访的复发情况并探讨影响复发的危险因素。方法 回顾性分析经过5年随访的169例近期应答者。记录患者临床及实验室资料、治疗方案和复发情况。采用Kaplan-Meier法计算累积复发率,χ2和t检验进行单因素分析,Cox回归进行多因素分析。结果 治疗结束后第1、2、3、4、5年的累积复发率分别为21.9%、 28.4%、 32.0%、33.1%、34.3%。单因素分析中,年龄、基线血清乙肝病毒脱氧核糖核酸(hepatitis B virus deoxyribonucleic acid,HBV DNA)水平、停药时血清乙肝表面抗原(hepatitis B surface antigen,HBsAg)水平、停药时血清HBsAg较基线下降程度、HBV基因型及干扰素疗程与复发相关。Cox回归显示,干扰素疗程与治疗结束时血清HBsAg水平RR(95% CI)分别为0.640(0.413~0.991)和1.789(1.218~2.629),是影响IFN-ɑ治疗近期应答者复发的主要指标。治疗结束时血清HBsAg≥2 lg IU/ml所得复发的阳性预测值(positive predictive value,PPV)和阴性预测值(negative predictive value,NPV)分别为49.5%和90.6%。结论 IFN-ɑ疗程过短和治疗结束时HBsAg水平仍高是近期应答者复发的危险因素,延长IFN-ɑ疗程可以降低复发风险,血清HBsAg定量有助于决定IFN-ɑ个体化治疗疗程。Abstract: Objective To estimate relapse of hepatitis B in HBeAg-positive chronic hepatitis B patients who accept standardized interferon-alpha α (IFN-α) regimen during 5-year follow-up observation and evaluate the factors influencing relapse of hepatitis B. Methods We retrospectively analyzed 169 initial responders to standardized IFN-α therapy during 5-year follow-up. The clinical data and laboratory data, treatment regimen and relapse of the illness were recorded. The Kaplan-Meier method was used to calculate cumulative relapse rate; The χ2 test, student's t test and Cox proportional hazards regression model were used to analyze the correlation between the potential risk factors and relapse. Results The cumulative relapse rates at 1, 2, 3, 4, and 5 year posttreatment were 21.9%, 28.4%, 32.0%, 33.1% and 34.3% respectively; Relapse was related to age, serum hepatitis B virus deoxyribonucleic acid (HBV DNA) and hepatitis B surface antigen (HBsAg) levels, decline in serum HBsAg levels at the end of treatment, HBV genotype and duration of IFN-α therapy by univariate analysis; According to Cox regression, duration of IFN-α therapy and serum HBsAg levels at the end of treatment were two main indicators for relapse of hepatitis B; The relative risk (RR) were 0.640 (95% CI:0.413-0.991) and 1.789 (95% CI:1.218-2.629) respectively. The positive predictive value (PPV) and negative predictive value (NPV) of serum HBsAg being 2 lg IU/ml or greater at end of treatment was 49.5% and 90.6% for prediction of relapse. Conclusions Shorter duration of IFN-α therapy and higher serum HBsAg levels at the end of treatment are risk factors for relapse of hepatitis B, prolongation of IFN-α therapy might reduce risk of relapse, and serum HBsAg quantification may be useful in determining course of individualized IFN-α treatment.
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Key words:
- Hepatitis B, Chronic /
- Interferon-alpha /
- Recurrence /
- Regression analysis
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