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恩替卡韦治疗慢性乙型肝炎患者血清HBV cccDNA和HBV pgRNA水平变化*
引用本文:王春莹,屈耀宁,乔炜,刘静静,胡颖辉. 恩替卡韦治疗慢性乙型肝炎患者血清HBV cccDNA和HBV pgRNA水平变化*[J]. 实用肝脏病杂志, 2022, 25(5): 641-644. DOI: 10.3969/j.issn.1672-5069.2022.05.009
作者姓名:王春莹  屈耀宁  乔炜  刘静静  胡颖辉
作者单位:710065 西安市 兵器工业五二一医院消化内科(王春莹,屈耀宁,乔炜);肿瘤血液科(刘静静);西安交通大学第一附属医院涉外病房(胡颖辉)
基金项目:陕西省卫生健康委员会科学技术研究基金资助项目(编号:2018SF-229)
摘    要:目的 探讨血清 HBV 共价闭合环状 DNA(HBV cccDNA)和HBV前基因组 RNA(HBV pgRNA)水平预测血清HBeAg阳性慢性乙型肝炎(CHB)患者接受恩替卡韦治疗后疗效的临床价值。方法 2018年1月~2020年1月我院收治的HBeAg阳性CHB患者89例,均口服恩替卡韦分散片治疗48 w。使用COOBAS TAQMAN和COBAS Amliprep系统和采用荧光定量PCR法检测血清HBV cccDNA和HBV pgRNA水平,采用化学发光法定量检测血清HBsAg和HBeAg水平。应用受试者工作特征曲线(ROC)分析血清各指标预测恩替卡韦治疗的CHB患者疗效的价值。结果 89例HBeAg阳性CHB患者经恩替卡韦治疗48 w后,获得病毒学应答85例(95.5%),生化学应答80例(89.9%),血清学应答9例(10.1%);获得完全应答75例(84.3%);完全应答组血清ALT、HBsAg、HBeAg、HBV DNA, HBV cccDNA和HBV pgRNA水平分别为(228.3±34.9)U/L、(2.5±0.4)lg IU/mL、(18.6±1.9)S/CO、(6.1±0.6)lg IU/mL、(2.2±0.2)cps/mL和(4.5±0.6)cps/mL,与非完全应答组【分别为(69.5±17.1)U/L、(3.7±0.7)lg IU/mL、(163.2±16.3)S/CO、(6.8±0.7)lg IU/mL、(3.9±0.4)cps/mL和(7.0±0.7)cps/mL】比,差异显著(P<0.05);应用血清HBV cccDNA与HBV pgRNA水平联合预测CHB患者接受恩替卡韦治疗疗效的ROC曲线下面积为0.892,其敏感性为81.6%,特异性为89.5%。结论 在抗病毒治疗前,检测HBeAg阳性慢性乙型肝炎患者血清HBV cccDNA和HBV pgRNA水平预测疗效有一定的应用价值,值得进一步研究。

关 键 词:慢性乙型肝炎  恩替卡韦  HBeAg  HBV共价闭合环状DNA  HBV前基因组RNA  治疗  
收稿时间:2021-12-23

Implication of serum HBV cccDNA and HBV pgRNA in patients with chronic hepatitis B receiving entecavir therapy
Wang Chunying,Qu Yaoning,Qiao Wei,et al.. Implication of serum HBV cccDNA and HBV pgRNA in patients with chronic hepatitis B receiving entecavir therapy[J]. Journal of Clinical Hepatology, 2022, 25(5): 641-644. DOI: 10.3969/j.issn.1672-5069.2022.05.009
Authors:Wang Chunying  Qu Yaoning  Qiao Wei  et al.
Affiliation:Department of Gastroenterology, 521st Hospital of Ordnance Industry, Xi’an 710065, Shaanxi Province, China
Abstract:Objective The aim of this study was to investigate the clinical implication of serum HBV covalently closed circular DNA (HBV cccDNA) and HBV pregenomic RNA (HBV pgRNA) in patients with chronic hepatitis B (HBV) undergoing entecavir therapy. Methods A total of 89 patients with serum HBeAg-positive CHB were admitted to our hospital between January 2018 and January 2020, and all received entecavir therapy for 48 weeks. Serum HBV cccDNA, HBV pgRNA and HBV DNA loads were detected by fluorescent quantitative PCR under COOBAS TAQMAN and COBAS Amliprep systems. Serum HBsAg and HBeAg levels were detected by chemiluminescence method. The predicting performance of each parameter was analyzed by receiver operating characteristic (ROC) curve. Results At the end of 48 week observation, the virologic response was obtained in 85 cases(95.5%), biochemical response was obtained in 80 cases (89.9%), and serologic response in 9 cases (10.1%); the complete response (CR) as defined by both virologic and biochemical responses was gained in 75 cases(84.3%); at presentation, serum ALT, HBsAg, HBeAg, HBV DNA, HBV cccDNA and HBV pgRNA levels in patients with CR were (228.3±34.9)U/L, (2.5±0.4)lg IU/mL, (18.6±1.9)S/CO, (6.1±0.6)lg IU/mL, (2.2±0.2)cps/mL and (4.5±0.6)cps/mL, significantly different compared to [(69.5±17.1)U/L, (3.7±0.7)lg IU/mL, (163.2±16.3)S/CO,(6.8±0.7)lg IU/mL, (3.9±0.4)cps/mL and (7.0±0.7)cps/mL, respectively, P<0.05]; the area under ROC of serum HBV cccDNA and HBV pgRNA combination in predicting CR in patients with CHB receiving entecavir treatment was 0.892, with the sensitivity of 81.6% and specificity of 89.5%. Conclusion The combined detection of serum HBV cccDNA and HBV pgRNA is of high predictive value in patients with HBeAg-positive CHB before antiviral therapy, which needs further clinical investigation.
Keywords:Hepatitis B  Entecavir  HBeAg positive  HBV cccDNA  HBV pgRNA  Therapy  
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