王洁　　朱姣娜　　陈公英　　刘静　　龚玲　　施军平

[關键词] 慢性乙型肝炎;慢性乙型肝炎表面抗原;肝炎e抗原;恩替卡韦;预测价值

[中图分类号] R512.62          [文献标识码] A          [文章编号] 1673-9701（2021）16-0027-05

The predictive value of HBsAg concentration on the therapeutic effect of entecavir in HBeAg-positive chronic hepatitis B patients

WANG Jie1   ZHU Jiaona2   CHEN Gongying1   LIU Jing1   GONG Ling1   SHI Junping1

1.The Affiliated Hospital of Hangzhou Normal University， Hangzhou   310000， China; 2.Ningbo Yinzhou NO.2 Hospital，Ningbo   315000， China

[Abstract] Objective To dynamically monitor the hepatitis B surface antigen （HBsAg） level in patients with hepatitis B e antigen （HBeAg） positive chronic hepatitis B （CHB） receiving entecavir （ETV） treatment， and to explore the predictive value of the early HBsAg concentration for treatment effect. Methods A total of 62 HBeAg-positive patients with chronic hepatitis B received entecavir antiviral treatment for one year. The hepatitis B virus （HBV） serum markers， deoxyribonucleic acid quantification（HBV DNA）， and alanine aminotransferase （ALT） were detected at 0， 4， 8， 12， 24， and 48 weeks. T-test， Pearson correlation analysis， and receiver operating characteristic （ROC） curve were used for analysis. Results 50 CHB patients had a virological response （VR+）， and 12 CHB patients did not have a virological response （VR-）. There was no significant difference in baseline of gender， age， ALT， and HBV DNA load between the two groups （P>0.05）. The lg HBsAg concentration in the VR+ group was lower than that in the VR-group [（4.103±0.459） vs. （4.611±0.259）， P=0.000]. Both groups of HBV-DNA decreased with the prolonged treatment time. The HBV DNA load in VR+ group was significantly lower than that in VR-group after treatment for 4 weeks， 8 weeks， 12 weeks， 24 weeks， and 48 weeks （P<0.05）. The lg HBsAg of the two groups decreased with the prolonged treatment time. The lg HBsAg of VR+ group was significantly lower than that of VR- group after treatment for 4 weeks， 8 weeks， 12 weeks， 24 weeks， and 48 weeks （P<0.05）. The area under the ROC curve of lg HBsAg concentration was the largest at 8 weeks of treatment （AUC=0.992， P<0.05）. The Youden index of cut-off value 3.945 IU/mL was the largest（0.960）. Conclusion The lg HBsAg≤3.945 IU/mL at 8 weeks of ETV treatment can be used as an index to predict the virological response of ETV treatment for one year.

[Key words] Chronic hepatitis B; Chronic hepatitis B surface antigen; Hepatitis e antigen; Entecavir; Predictive value

乙型病毒性肝炎是由乙型肝炎病毒（Hepatitis B virus，HBV）引起的一类常见肝病，流行病学调查结果显示，全球约2.5亿人为慢性HBV感染者[1]，有15%～40%发展为肝衰竭、肝硬化和肝细胞癌（Hepatocellular carcinoma，HCC）[2]。调查显示，我国1～59岁一般人群乙型病毒性肝炎表面抗原（Hepatitis B surface antigen，HBsAg）携带率为7.18%[3-4]。据此推算，我国现有慢性HBV感染者约9300万人，其中慢性乙型肝炎患者约2000万例[5]。目前慢性乙型肝炎患者的治疗以抗病毒为主，恩替卡韦已逐渐成为我国目前主要的一线抗病毒药物，如何通过对早期治疗反应的观察，从而进一步优化治疗以提高远期疗效，预防肝硬化、肝癌的发生成为新的研究热点。据报道，HBsAg水平或治疗期间HBsAg水平与机体的长期病毒学应答、血清学应答及HBsAg阴转状况有良好的相关性[6]。本研究对62例ETV治疗的HBeAg阳性 CHB患者随访1年，动态监测恩替卡韦（Entecavir，ETV）治疗前后HBsAg浓度、乙肝脱氧核糖核酸（Hepatitis B deoxyribonucleic acid，HBV DNA）载量、丙氨酸氨基转移酶（Alanine aminotransferase，ALT）水平的变化，探讨HBsAg浓度对HBeAg阳性的HBV患者恩替卡韦治疗效果的预测价值，现报道如下。

1 资料与方法

1.1 一般资料

选择2014年1月至2017年11月在杭州师范大学附属医院肝病科住院及门诊接受恩替卡韦初治（0.5 mg/d）的HBeAg阳性CHB患者62例，其中男47例，女15例，每例收集6个时间点（0、4、8、12、24、48周）的血清样本。纳入标准：①诊断标准符合2015年《慢性乙型肝炎防治指南》[7]者;②年龄18～65岁，有能力理解和签署知情同意书者;③HBsAg阳性≥6个月，且HBeAg阳性者;④HBV DNA≥2×104 IU/mL者;⑤血清ALT>2倍正常值上限者。排除……