Predictive value of HBcrAg for lamivudine resistance in patients with chronic hepatitis B
摘要: 目的评价乙型肝炎核心相关抗原（HBcrAg）对慢性乙型肝炎患者拉米夫定（LAM）耐药的预测作用。方法收集2009年1月至2011年12月期间住院和门诊收治的43例慢性乙型肝炎初治患者,拉米夫定治疗≥6个月,随访≥6个月,根据随访期间HBV DNA测序结果分为耐药组21例,非耐药组22例。分别检测各研究节点ALT、HBsAg、HBeAg、HBcrAg、HBV DNA水平。计量资料两组间比较采用独立样本t检验,方差不齐采用Mann-Whitney U检验;计数资料采用卡方检验。相关性分析采用Spearman分析。影响因素采用Logistic回归分析。结果 LAM抗病毒前HBcrAg与HBV DNA水平有较好的一致性,Spearman相关系数为0.863（P<0.001）。LAM抗病毒治疗后,外周血HBcrAg与HBV DNA水平均有所下降,但HBcrAg下降速度与幅度均低于HBV DNA。Logistic回归分析显示,随访结束时HBcrAg水平可能为LAM耐药的影响因素（P<0.01）。HBcrAg对LAM耐药预测价值较高,ROC曲线下面积为0.872（P<0.001）。...Abstract: Objective To evaluate the predictive value of hepatitis B virus ( HBV) core- related antigen ( HBcrAg) for the lamivudine ( LAM) resistance in patients with chronic hepatitis B. Methods Forty- three patients with previously untreated chronic hepatitis B who were treated in the inpatient department and outpatient department from January 2009 to December 2011 were enrolled. These patients received treatment with LAM for at least 6 months and were then followed up for at least 6 months. They were divided into resistance group ( n= 21) and non- resistance group ( n = 22) according to the HBV DNA sequencing results during follow up. ALT, HBsAg, HBeAg, HBcrAg, and HBV DNA levels at different time points were measured. Comparison of continuous data between the two groups was made by independent- samples t test, and Mann- Whitney U test was used if heterogeneity of variance was identified; categorical data were analyzed by chi- square test; correlations were determined by Spearman analysis; the influential factors were determined by logistic regression analysis. Results Before treatment with LAM, there was a significant positive correlation between the HBcrAg and HBV DNA levels in peripheral blood ( Spearman correlation coefficient r = 0. 863, P < 0. 001) . After the initiation of LAM therapy, both HBcrAg and HBV DNA levels decreased, and the decrease in HBcrAg level was significantly slower and smaller than that in HBV DNA level. The logistic regression analysis showed that HBcrAg level at the end of follow- up might be an influential factor for LAM resistance ( P < 0. 01) . HBcrAg had a high predictive value for LAM resistance, with an area under the ROC curve of 0. 872 ( P < 0. 001) . Conclusion There is a significant positive correlation between HBcrAg and HBV DNA levels in peripheral blood before LAM administration, and the HBcrAg level at the end of follow-up has a high predictive value for LAM resistance in patients with chronic hepatitis B.
European Association for the Study of the Liver.EASL clinical practice guidelines:management of chronic hepatitis B[J].J Hepatol, 2009, 50 (2) :227-242.LAI CL, RATZIU V, YUEN MF, et al.Viral hepatitis B[J].Lancet, 2003, 362 (9401) :2089-2094.Lamivudine Clinical Practice Group.Lamivudine treatment consensus from relative experts in 2004[J].J Clin Hepatol, 2005, 8 (1) :60-64. (in Chinese) 拉米夫定临床应用专家组.拉米夫定临床应用专家共识 (2004年版) [J].实用肝脏病杂志, 2005, 8 (1) :60-64.QIN H, CHENG XF, TENG X, et al.Study mutation in Heilongjiang province[J].Int J Virol, 2012, 19 (1) :15-19. (in Chinese) 秦辉, 程险峰, 滕旭, 等.黑龙江省乙型肝炎病毒拉米夫定耐药株YMDD变异与基因型、BCP区变异的相关性研究[J].国际病毒学杂志, 2012, 19 (1) :15-19.USUDA S, OKAMOTO H, TSUDA F, et al.An enzyme-linked immunosorbent assay with monoclonal antibodies for the determination of phosphorylated hepatitis B core protein (p21c) in serum[J].J Virol Methods, 1998, 72 (1) :95-103.KIMURA, TA, ROKUHARA Y, SAKAMOTO S, et al.Sensitive enzyme immunoassay for hepatitis B virus core-related antigens and their correlation to virus load[J].J Clin Microbiol, 2002, 40 (2) :439-445.Chinese Society of Infectious and Parasitic Diseases, Chinese Society of Hepatology.Prevention and treatment programs in viral hepatitis[J].Chin J Hepatol, 2000, 8 (6) :324-329. (in Chinese) 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.MARZANO A, GAIA S, GHISETTI V, et al.Viral load at the time of liver transplantation and risk of hepatitis B virus recurrence[J].Liver Transpl, 2005, 11 (4) :402-409.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[J].Gastroenterology, 2004, 126 (7) :1750-1758.LOK ASF, McMAHON BJ.Chronic hepatitis B:update 2009[J].Hepatology, 2009, 50 (3) :1-36.YUEN MF, WONG DK, SUM SS, et al.Effect of lamivudine therapy on the serum covalently closed circular (ccc) DNA of chronic hepatitis B infection[J].Am J Gastroenterol, 2005, 100 (5) :1099-1110.HAMADA R, NAKAO R, HAI N, et al.Hepatitis B virus corerelated antigen as an indicator of safe discontinuation of lamivudine therapy[J].Hepatology, 2006, 44 (4) :562a.LIU C, MU YP, YANG ZG, et al.Clinical significance of monitoring hepatitis B virus core-related antigens[J].J Clin Hepatol, 2012, 28 (10) :793-796. (in Chinese) 刘成, 慕永平, 杨宗国, 等.乙型肝炎病毒核心相关抗原的监测及临床意义[J].临床肝胆病杂志, 2012, 28 (10) :793-796.MATSUMOTO A, TANAKA E, SUZUKI Y, et al.Combination of hepatitis B viral antigens and DNA for prediction of relapse after discontinuation of nucleos (t) ide analogs in patients with chronic hepatitis B[J].Hepatol Res, 2012, 42 (2) :139-149.
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