血清HBsAg和HBeAg水平变化与慢性乙型肝炎患者抗病毒疗效预测

doi:10.3969/j.issn.1672-5069.2014.01.032

摘要/Abstract

摘要： 血清HBsAg或HBeAg定量水平的变化在慢性乙型肝炎（CHB）患者抗病毒治疗的应答中有重要预测价值,可以用于指导和调整治疗方案。本文综述了CHB患者血清HBsAg和HBeAg水平变化与HBV复制指标如血清HBV DNA和肝内HBV cccDNA间的关系,以阐明CHB患者血清HBsAg或HBeAg水平在判定抗病毒疗效方面的新认识。

关键词: 慢性乙型肝炎, 乙型肝炎病毒, HBsAg, HBeAg, 抗病毒治疗

Abstract: Quantification of serum HBsAg and HBeAg in patients with CHB is useful in the prediction of response to antiviral treatment, and they can be used to guide the treatment strategy. Here we reviewed the changes in serum HBsAg and HBeAg levels in patients with CHB and their relations to HBV replication, which include serum HBV DNA, and intrahepatic HBV cccDNA. This review will help to understand the clinical value of serum HBsAg and HBeAg levels in the prediction of antiviral efficacy in patients with CHB.

Key words: Chronic hepatitis B, Hepatitis B virus, HBsAg, HBeAg, Antiviral treatment

林沪综述李元元, 王福生审校. 血清HBsAg和HBeAg水平变化与慢性乙型肝炎患者抗病毒疗效预测[J]. 实用肝脏病杂志, 2014, 17(1): 98-102.

Lin Hu, Li Yuanyuan, Wang Fusheng. Serum HBsAg and HBeAg levels in the prediction of antiviral efficacy in patients with chronic hepatitis B[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2014, 17(1): 98-102.

参考文献

[1] Lau GK,Piratvisuth T,Luo KX,et al. Peginterferon alfa-2a HBeAg-positive chronic hepatitis B study group. Peginterferon alfa-2a,lamivudine,and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med,2005,352（26）：2682-2695.
[2] 中华医学会肝病学分会和感染病学分会.慢性乙型肝炎防治指南（2010年版）. 实用肝脏病杂志,2011,14（2）：81-89.
[3] Moucari R,Mackiewicz V,Lada O,et al. Early serum HBsAg drop：a strong predictor of sustained virological response to pegylated interferon alfa-2a in HBeAg-negative patients. Hepatology,2009,49：1151-1157.
[4] Brunetto MR,Moriconi F,Bonino F,et al. Hepatitis B virus surface antigen levels：a guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B. Hepatology,2009,49：1141-1150.
[5] Lang T,Lo C,Skinner N,et al. The hepatitis B e antigen （HBeAg） targets and suppresses activation of the toll-like receptor signaling pathway. J Hepatol,2011,55（4）：762-769.
[6] Lau G,Marcellin P,Peters M. Chronic hepatitis B：a global health problem requiring coherent worldwide treatment strategies. Hepatol Int,2007,1（2）： 316-325.
[7] Yuen MF. Revisiting the natural history of chronic hepatitis B：impact of new concepts on clinical management. J Gastroenterol Hepatol,2007,22（7）：973-976.
[8] Fried MW,Piratvisuth T,Lau GK,et al. 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.
[9] 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.
[10] Lu H,Geng DY,Shen F,et al. Optimization of adefovir therapy in chronic hepatitis B according to baseline predictors and on-treatment HBV DNA：a 5-year prospective study. Virol J, 2011,21（8）：444.
[11] Yen YH,Lu SN,Chen CH,et al. Changes in serum hepatitis B e antigen（HBeAg） levels associated with the emergence of YMDD mutants in HBeAg non-seroconverted patients during lamivudine therapy. Liver Int,2007,27（10）：1349-1355.
[12] Thompson AJ,Nguyen T,Iser D,et al. Serum hepatitis B surface antigen and hepatitis B e antigen titers： disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology,2010,51：1933-1944.
[13] Michael FW,Teerha P,George KL,et al.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.
[14] Lim SG,Cheng Y,Guindon S,et al. Viral quasispecies evolution during hepatitis Be antigen seroconversion. Gastroenterology,2007,133（3）：951-958.
[15] Nguyen T,Thompson AJ,Bowden S,et al. Hepatitis B surface antigen levels during the natural history of chronic hepatitis B：A perspective on Asia. J Hepatol,2010,52（4）：508-513.
[16] Kim YJ,Cho HC,Choi MS,et al. The change of the quantitative HBsAg level during the natural course of chronic hepatitis B. Liver Int,2011,31（6）：817-823.
[17] Chan HL,Wang H,Niu J,et al. Two-year lamivudine treatment for hepatitis B e antigen-negative chronic hepatitis B：A double-blind,placebo-controlled trial. Antiviral Ther,2007,12（3）：345-353.
[18] Werle-Lapostolle B,Bowden S,Locarnini S,et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology,2004,126（7）：1750-1758.
[19] Wursthorn K,Lutgehetmann M,Dandri M,et al. Peginterferon alpha-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis B. Hepatology,2006,44（3）：675-684.
[20] Lau GK,Marcellin P,Brunetto M,et al. On-treatment monitoring of HBsAg levels to predict response to peginterferon alfa-2a in patients with HBeAg-positive chronic hepatitis. J Hepatol,2009,50：S333.
[21] Brunetto MR,Moriconi F,Bonino F,et al. 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）：1141-1450.
[22] Moucari R,Mackiewicz V,Lada O,et al. 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.
[23] Lu L,Ye DW,Wang YD,et al. Relationship between HBV cccDNA and HBsAg levels is associated with HBeAg status of chronic hepatitis B patients. J Hepatol,2009,50：S209.
[24] Lin LY,Wong VW,Zhou HJ,et al. Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients. J Med Virol,2010,82（9）：1494-1500.
[25] Manesis EK,Papatheodoridis GV,Tiniakos DG,et al. Hepatitis B surface antigen：Relation to hepatitis B replication parameters in HBeAg-negative chronic hepatitis B. J Hepatol,2011,55（1）：61-68.
[26] Ganji A,Esmaeilzadeh A,Ghafarzadegan K,et al. Correlation between HBsAg quantitative assay results and HBV DNA levels in chronic HBV. Hepat Mon,2011,11（5）：342-345.
[27] Lim SG,Cheng Y,Guindon S,et al. Viral quasispecies evolution during hepatitis B e antigen seroconversion. Gastroenterology,2007,133（3）：951-958.
[28] Volz T,Lutgehetmann M,Wachtler P,et al. Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients. Gastroenterology,2007,133（3）：843-852.
[29] Laras A,Koskinas J,Dimou E,et al. Intrahepatic levels and replicative activity of covalently closed circular hepatitis B virus DNA in chronically infected hepatitis B surface antigen quantitation can reflect hepatitis B virus in the liver and predict treatment response. Clin Gastroenterol Hepatol,2007,5（12）：1462-1468.
[31] Marcellin P,Bonino F,Lau GK,et al. Peginterferon alfa-2a in HBeAg-negative chronic hepatitis B study group. Sustained response of hepatitis B e antigen-negative patients 3 years after treatment with peginterferon alpha-2a. Gastroenterology,2009,136（7）：2169-2179.e1-4.
[32] Rijckborst V,Hansen BE,Cakaloglu Y,et al. Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels. Hepatology,2010,52（2）：454-461.
[33] 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. Hepatology,2010,52（4）：1251-1257.
[34] Liaw YF. Clinical utility of hepatitis B surface antigen quantitation in patients with chronic hepatitis B：a review. Hepatology, 2011,53（6）：2121-2129.
[35] Chan HL,Thompson A,Martinot-Peignoux M,et al. Hepatitis B surface antigen quantification：why and how to use it in 2011- a core group report. J Hepatol,2011,55（5）：1121-1131.