α-干扰素治疗慢性乙型肝炎疗效预测因素研究进展

doi:10.3969/j.issn.1672-5069.2015.05.032

摘要/Abstract

摘要： α-干扰素主要通过抑制病毒复制和调节免疫功能而发挥抗病毒作用。在实际临床应用中，α-干扰素治疗慢性乙型肝炎的总有效率仅为30％～40％。研究发现，宿主血清丙氨酸氨基转移酶水平、肝脏病理学损害程度、机体免疫状态、遗传背景以及病毒基因分型、病毒变异、血清HBV DNA、HBsAg、HBeAg、HBcAb水平可以预测干扰素的疗效。采用多因素联合对α-干扰素疗效进行预测，可以优化治疗、提高疗效，以获得最大价格效益比。

关键词: 慢性乙型肝炎, α-干扰素, 疗效预测

Abstract: Interferon-alpha（IFN-α） plays a antiviral role mainly through inhibiting virus replication and regulating immune function. In clinical practice，the effective rate of IFN-αtreatment in patients with chronic hepatitis B （CHB） is only 30% to 40%. There are many factors，such as serum alanine aminotransferase（ALT） level，hepatic pathological status，immune function， genetic background，and viral genotype，virus mutation，serum level of HBV DNA，HBsAg，HBeAg and HBcAb，which can predict the efficacy of IFN-αtherapy. We should take a variety of factors into consideration when we predict the efficacy of IFN-αtreatment in order to optimize the therapy regimen and to improve the viral response.

Key words: Chronic hepatitis B, Interferon-alpha, Efficacy predicting

郭远，陈从新. α-干扰素治疗慢性乙型肝炎疗效预测因素研究进展[J]. 实用肝脏病杂志, 2015, 18(5): 558-562.

Guo Yuan，Chen Congxin. Factors predicting the efficacy of interferon-alpha efficacy in treatment of patients with chronic hepatitis B[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2015, 18(5): 558-562.

参考文献

[1] Buster EH，Hansen BE，Lau GK，et al. Factors that predict response of patients with hepatitis B e antigen-positive chronic hepatitis B to peginterferon-alfa. Gastroenterology，2009，137（6）:2002-2009.
[2] 占国清，谭华炳，谢杏榕，等. α干扰素治疗HBeAg阳性慢性乙型肝炎疗效的预测指标.胃肠病学和肝病学杂志，2011，20（7）：663-665.
[3] 杨正德，万谟彬，爱翠，等. 慢性乙型肝炎患者肝病理学检查在预测干扰素抗病毒疗效中的意义.第二军医大学学报，2001，22（3）：263-264.
[4] 辛杰晶，潘修成，毛娟娟，等. α-干扰素治疗慢性乙型肝炎患者外周血调节性T细胞比例及单核细胞程序性死亡受体-1配体表达的变化及意义. 徐州医学院学报，2011，31（3）：163-165.
[5] 黄芳，龚环宇，鲁猛厚. 聚乙二醇干扰素治疗HBeAg阳性慢性乙型肝炎患者外周血NKT细胞的变化及疗效预测. 中国感染控制杂志，2013，12（2）：88-91.
[6] Xiao C，Qin B，Chen L，et a1. Preactivation of the interferon signalling in liver is correlated with nonresponse to interferon alpha therapy in patients chronically infected with hepatitis B virus. J Viral Hepat，2012，19（2）:e1-10．
[7] Zhu Y，Qin B，Xiao C，et a1. Cell-type specific interferon stimulated gene staining in liver underlies response to interferon therapy in chronic HBV infected patients. Dig Dis Sci，2012，57（9）:2355-2361．
[8] 马为民，陆坚，蒋小玲，等. 干扰素α- l b治疗慢性乙型肝炎的疗效及其预测因素分析. 中华传染病杂志，2001，19（3）：148-151.
[9] Tan AT，Koh S，Goh W，et al. A longitudinal analysis of innate and adaptive immune profile during hepatic flares in chronic hepatitis B. J Hepatol，2010，52（3）:330-339.
[10] Lee IC，Huang YH，Su CW，et al. CXCL9 associated with sustained virological response in chronic hepatitis B patients receiving peginterferon alfa-2a therapy:a pilot study.PLoS One，2013，8（10）:e76798.
[11] 刘劲阳.干扰素中和抗体和CHB患者抗病毒疗效之间的关系.中外医疗，2010，29（26）：31-32.
[12] Tseng TC，Yu ML，Liu CJ，et al. Effect of host and viral factors on hepatitis B e antigen-positive chronic hepatitis B patients receiving pegylated interferon-α-2a therapy. Antivir ther，2011，16（5）:629-637.
[13] Wu X，Zhu X，Zhu S，et al. A pharmacogenetic study of polymorphisms in interferon pathway genes and response to interferon-alpha treatment in chronic hepatitis B patients. Antiviral Res，2009，83（3）:252-256.
[14] 黄雁翔，马丽娜，陈新月，等. 粘病毒抵抗蛋白A和真核细胞起始因子2α调节区2基因多态性与慢性乙型肝炎干扰素治疗效果的相关性. 中华肝脏病杂志，2007，15（3）：187-191.
[15] King JK，Yeh SH，Lin MW，et al. Genetic polymorphisms in interferon pathway and response to interferon treatment in hepatitis B patients:A pilot study. Hepatology，2002，36（6）:1416-1424.
[16] Lampertico P，Viganò M，Cheroni C，et al. IL28B polymorphisms predict interferon-related hepatitis B surface antigen seroclearance in genotype D hepatitis B e antigen-negative patients with chronic hepatitis B. Hepatology，2013，57（3）:890-896.
[17] Boglione L，Cusato J，Allegra S，et al. Role of IL28-B polymorphisms in the treatment of chronic hepatitis B HBeAg-negative patients with peginterferon. Antiviral Res，2014，102:35-43.
[18] de Niet A，Takkenberg RB，Benayed R，et al. Genetic variation in IL28B and treatment outcome in HBeAg-positive and -negative chronic hepatitis B patients treated with peginterferon alfa-2a and adefovir. Scand J Gastroenterol，2012，47（4）:475-481.
[19] Galmozzi E，Viganò M，Lampertico P. Systematic review with meta-analysis:do interferon lambda 3 polymorphisms predict the outcome of interferon-therapy in hepatitis B infection Aliment Pharmacol Ther，2014，39（6）:569-578.
[20] 吴海清，赵钢德，李凤棣，等. 干扰素β启动子刺激因子1基因多态性与HBeAg阳性慢性乙型肝炎患者聚乙二醇干扰素α治疗应答的关系. 临床肝胆病杂志，2014，30（8）：757-763.
[21] Janssen HL，van Zonneveld M，Senturk H，et a1. Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B:a randomised trial.Lancet，2005，365（9454）:123-129．
[22] Buster EH，Flink HJ，Cakaloglu Y，et a1. Sustained HBeAg and HBsAg loss after long-term follow-up of HBeAg-positive patients treated with peginterferon alpha-2b. Gastroenterology，2008，135（2）:459-467．
[23] 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. Antivir Ther，2012，17（1）:9-17.
[24] 高国生，徐晓珍，胡耀仁，等. 乙型肝炎病毒基因型与聚乙二醇干扰素α治疗HBeAg阳性慢性乙型肝炎疗效的关系.中华内科杂志，2013，52（12）：1009-1012.
[25] Sonneveld MJ，Rijckborst V，Zeuzem S，et al. Presence of precore and core promoter mutants limits the probability of response to peginterferon in hepatitis B e antigen-positive chronic hepatitis B.Hepatology，2012，56（1）:67-75.
[26] European Association for the Study of the Liver. EASL Clinical Practice Guidelines:Management of chronic hepatitis B virus infection. J Hepatol，2012，57（1）:167-185.
[27] 安宝燕，蔡伟，王晖，等. 聚乙二醇干扰素α-2b治疗HBeAg阳性慢性乙型肝炎患者的疗效及影响因素.肝脏，2013，18（3）：146-149.
[28] 戚园，邵江波，吴迪. 肝组织cccDNA的检测在干扰素治疗慢性乙型肝炎患者中的应用. 中国医药指南，2012，10（36）：84-85.
[29] Takkenberg B，Terpstra V，Zaaijer H，et al. Intrahepatic response markers in chronic hepatitis B patients treated with peginterferon alpha-2a and adefovir.J Gastroenterol Hepatol，2011，26（10）:1527-1535.
[30] Liaw YF，Jia JD，Chan HL，et a1. Shorter durations and lower doses of peginterferon alfa-2a are associated with inferior hepatitis B e antigen seroconversion rates in hepatitis B virus genotypes B or C.Hepatology，2011，54（5）:1591-1599．
[31] Sonneveld MJ，Hansen BE，Piratvisuth T，et al. Response-guided peginterferon therapy in hepatitis B e antigen-positive chronic hepatitis B using serum hepatitis B surface antigen levels. Hepatology，2013，58（3）:872-880.
[32] Moucari R，Mackiewicz V，Lada O，et a1. Early serum HBsAg drop:a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology，2009，49（4）:1151-1157．
[33] 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. Hepatology，2009，49（4）:1141-1150．
[34] Rijckborst V，Ferenci P，Akdogan M，et al. Long-term follow-up of hepatitis B e antigen-negative patients treated with peginterferon a-2a:progressive decrease in hepatitis B surface antigen in responders. Eur J Gastroenterol Hepatol，2012，24（9）:1012-1019.
[35] Gheorghita VI，Caruntu FA，Curescu M，et al. Use of quantitative serum HBsAg for optimization of therapy in chronic hepatitis B patients treated with pegylated interferon alfa-2a:a Romanian cohort study. J Gastrointestin Liver Dis，2013，22（1）:27-32.
[36] Tangkijvanich P，Komolmit P，Mahachai V，et al. Comparison between quantitative hepatitis B surface antigen hepatitis B e-antigen and hepatitis B virus DNA levels for predicting virological response to pegylated interferon-alpha-2b therapy in hepatitis B e-antigen-positive chronic hepatitis B. Hepatol Res，2010，40（4）:269-277.
[37] 李磊，李宜，高人焘. HBsAg和HBeAg定量在干扰素治疗HBeAg阳性慢性乙型肝炎疗效预测中的价值.实用肝脏病杂志，2012，15（3）：232-234.
[38] Fried MW，Piratvisuth T，Lau GK，et a1. HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa-2a for HBeAg-positive chronic hepatitis B.Hepatology，2008，47（2）:428-434．
[39] Ma H，Yang RF，Wei L. Quantitative serum HBsAg and HBeAg are strong predictors of sustained HBeAg seroconversion to pegylated interferon alfa-2b in HBeAg-positive patients. J Gastroenterol Hepatol，2010，25（9）:1498-506.
[40] 纪永健，李菲菲，任万华，等. HBeAg早期下降对聚乙二醇干扰素α-2a治疗HBeAg阳性慢性乙型肝炎的疗效预测.中华肝脏病杂志，2013，21（5）：335-339.
[41] Hou FQ，Song LW，Yuan Q，et al. Quantitative hepatitis B core antibody level is a new predictor for treatment response in HBeAg-positive chronic hepatitis B patients receiving peginterferon.Theranostics，2015，5（3）:218-226.