α-干扰素治疗HBeAg阳性慢性乙型肝炎5年随访与复发因素分析

郭远; 宋海燕; 张骏飞; 董静; 潘劲劲; 陈照林; 陈曦; 刘波; 陈从新

doi:10.16462/j.cnki.zhjbkz.2016.03.007

α-干扰素治疗HBeAg阳性慢性乙型肝炎5年随访与复发因素分析

doi: 10.16462/j.cnki.zhjbkz.2016.03.007

安徽医科大学附属解放军临床学院, 解放军第105医院感染病科, 安徽合肥 230031

基金项目:

南京军区联勤部卫生部第十二五重大攻关课题（10Z007-A）

详细信息

作者简介:
郭远(1990-),女,湖北仙桃人,在读硕士研究生。主要研究方向:病毒性肝炎的基础与临床。

中图分类号: R512.26; R181
计量
- 文章访问数: 276
- HTML全文浏览量: 62
- PDF下载量: 69
- 被引次数: 0
出版历程
- 收稿日期: 2015-11-15
- 修回日期: 2016-01-23

Relapse of hepatitis B e antigen-positive patients after standardized interferon α regimen: A five-year follow-up study

Department of Infectious Diseases, 105th Hospital, PLA Clinical College Affiliated to Anhui Medical University, Hefei 230031, China

摘要

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。
- 肝炎,乙型,慢性 /
- 干扰素α /
- 复发 /
- 回归分析
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.
- Hepatitis B, Chronic /
- Interferon-alpha /
- Recurrence /
- Regression analysis

HTML全文

参考文献(16)

European Association for the Study of the Liver. EASL clinical practice guidelines: management of chronic hepatitis B virus infection [J]. J Hepatol, 2012,57(1):167-185.

Seeger C, Mason WS. Hepatitis B virus biology [J]. Microbiol Mol Biol Rev, 2000,64(1):51-68.

刘定立,骆抗先,冯筱榕,等. 慢性乙型肝炎干扰素治疗后长期随访中复发与相关因素的研究 [J]. 南方医科大学学报, 2007,27(8):1264-1270.

中华医学会肝病学分会和中华医学会感染病学分会. 慢性乙型肝炎防治指南(2010年版) [J]. 中华肝脏病杂志(电子版), 2011,3(1):40-56.

袁敏,张振华,张礼周,等. IFN-ɑ治疗慢性乙型肝炎中出现HBeAg血清学转换的预测因素分析 [J]. 中华疾病控制杂志, 2014,18(7):606-609.

中华医学会传染病与寄生虫病学分会,肝病学分会. 病毒性肝炎防治方案 [J]. 中华肝脏病杂志, 2000,8(6):324-329.

占国清,谭华炳,李芳,等. ɑ-干扰素治疗慢性乙型肝炎完全应答后5年随访报告 [J]. 实用肝脏病杂志, 2014,17(4):380-383.

Song BC, Suh DJ, Lee HC, et al. Which patients with chronic hepatitis B are more likely to relapse after interferon alpha-induced hepatitis B e antigen loss in Korea? [J]. J Clin Gastroenterol, 2004,38(2):124-129.

Newbold JE, Xin H, Tencza M, et al. The covalently closed duplex form of the hepadnavirus genome exists in situ as a heterogeneous population of viral minichromosomes [J]. J Virol, 1995,69(6):3350-3357.

Carey I, Bruce M, Horner M, et al. HBsAg plasma level kinetics: a new role for an old marker as a therapy response predictor in vertically infected children on combination therapy [J]. J Viral Hepat, 2015,22(4):441-452.

Brunetto MR, Moriconi F, Bonino F, et a1. Hepatitis B virus surface antigen levels: a guide to sustained response to peginterferon alfa-2a in HBeAg- negative chronic hepatitis B [J]. Hepatology, 2009,49(4):1141-1150.

Suzuki F, Arase Y, Suzuki Y, et al. Long-term efficacy of interferon therapy in patients with chronic hepatitis B virus infection in Japan [J]. J Gastroenterol, 2012,47(7):814-822.

Sonneveld MJ, Rijckborst V, Cakaloglu Y, et al. Durable hepatitis B surface antigen decline in hepatitis B e antigen-positive chronic hepatitis B patients treated with pegylated interferon-α2b: relation to response and HBV genotype [J]. Antivir Ther, 2012,17(1):9-17.

Rijckborst V, Ferenci P, Akdogan M, et al. Long-term follow-up of hepatitis B e antigen-negative patients treated with peginterferon α-2a: progressive decrease in hepatitis B surface antigen in responders [J]. Eur J Gastroenterol Hepatol, 2012,24(9):1012-1019.

Sonneveld MJ, Rijckborst V, Boucher CA, et al. Prediction of sustained response to peginterferon alfa-2b for hepatitis B e antigen-positive chronic hepatitis B using on-treatment hepatitis B surface antigen decline [J]. Hepatology, 2010,52(4): 1251-1257.

Buster EH, Flink HJ, Cakaloglu Y, et al. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b [J]. Gastroenterology, 2008,135(2):459-467.

施引文献

资源附件(0)

访问统计