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血清乙型肝炎病毒前基因组RNA水平对核苷(酸)类似物初治的慢性乙型肝炎患者疗效预测价值*
引用本文:严景全,王春玲,刘娟,卢雪兰,林占洲,莫凡.血清乙型肝炎病毒前基因组RNA水平对核苷(酸)类似物初治的慢性乙型肝炎患者疗效预测价值*[J].实用肝脏病杂志,2022,25(1):22-25.
作者姓名:严景全  王春玲  刘娟  卢雪兰  林占洲  莫凡
作者单位:516001 广东省惠州市中心人民医院肝病内科(严景全,王春玲,刘娟,卢雪兰,林占洲);广东医科大学附属医院肝病内科(莫凡)
基金项目:广东省自然科学基金资助项目(编号:2018A030313550)。
摘    要:目的 探讨应用血清乙型肝炎病毒前基因组RNA(HBV pgRNA)水平预测核苷(酸)类似物初治的慢性乙型肝炎(CHB)患者疗效的价值。方法 2015年8月~2019年12月我院诊治的初始治疗的CHB患者107例,接受恩替卡韦、替诺福韦或替比夫定治疗观察48 w。采用实时荧光定量PCR法检测血清HBV pgRNA,采用ELISA法检测血清HBsAg和HBeAg。应用Logistic回归分析影响疗效的因素,应用MedCalc1 5.1统计学软件绘制ROC,计算曲线下面积(AUC)评价血清HBV pgRNA水平预测核苷(酸)类似物治疗的疗效。结果 在治疗48周末,27例(25.2%)患者不应答,另80例(74.8%)患者获得完全应答或部分应答;(完全或部分)应答组血清HBV DNA载量为(6.1±1.0)lg copies/mL,显著低于不应答组【(7.2±1.2) lg copies/mL,P<0.05】,外周血CD4/CD8比值为(0.7±0.2),显著高于不应答组【(0.6±0.1),P<0.05】,血清HBeAg阳性率为41.3%,显著低于不应答组(70.4%,P<0.05),血清HBV pgRNA水平为(5.3±0.8)lg copies/mL,显著低于不应答组【(6.5±1.1)lg copies/mL,P<0.05】;Logistic回归分析显示,基线HBV DNA载量、HBeAg状态和血清HBV pgRNA水平均为影响核苷(酸)类似物治疗的CHB患者疗效的因素(OR=2.793、OR=3.827、OR=4.035,P均<0.05);经ROC分析显示,血清HBV pgRNA水平预测核苷(酸)类似物治疗CHB患者不应答的最佳截断点为5.89 lgcopies/mL,AUC值为0.865(95%CI:0.816~0.905),其预测的灵敏度为74.1%(20/27),特异度为88.8%(71/80)。结论 监测血清HBV pgRNA水平预测核苷(酸)类似物初治的CHB患者的疗效有一定的临床应用价值,如果检测结果稳定,不失为一种临床决策的参考依据。

关 键 词:乙型肝炎  HBV前基因组RNA  核苷(酸)类似物  疗效预测  
收稿时间:2021-03-23

Predictive value of antiviral response by serum hepatitis B virus pregenomic RNA levels in na ve patients with hepatitis B receiving nucleos(t)ide analogues treatment
Yan Jingquan,Wang Chunling,Liu Juan,et al.Predictive value of antiviral response by serum hepatitis B virus pregenomic RNA levels in na ve patients with hepatitis B receiving nucleos(t)ide analogues treatment[J].Journal of Clinical Hepatology,2022,25(1):22-25.
Authors:Yan Jingquan  Wang Chunling  Liu Juan  
Affiliation:Department of Liver Diseases, Central People's Hospital, Huizhou 516001,Guangdong Province,China
Abstract:Objective The aim of this study was to explore the predictive value of antiviral response by serum hepatitis B virus(HBV)pregenomic RNA(pgRNA)levels in na ve patients with hepatitis B receiving nucleos(t)ide analogues treatment.Methods 107 na ve patients with chronic hepatitis B(CHB)were enrolled in our hospital between August 2015 and December 2019,and all were treated with nucleos(t)ide analogues,e.g.entecarvir,tenofovir,or telbivodine,for 12 months.Serum HBV pgRNA loads was assayed by real-time fluorescent quantitative PCR,serum HBsAg and HBeAg were detected by ELISA,the multivariate Logistic regression model was applied to analyze the influencing factors of response in CHB patients to nucleos(t)ide analogue treatment,and the area under the receiver operating characteristic curve(AUROC)was applied to predict the antiviral response by serum HBV pgRNA levels in CHB patients receiving nucleos(t)ide analogue treatment.Results At the end of 48 week observation,27 patients(25.2%)didn’t response to antiviral therapy,but 80 patients(74.8%)obtained complete or partial response;serum HBV DNA loads in patients with CR and PR was(6.1±1.0)lg copies/mL,significantly lower than(7.2±1.2)lg copies/mL,P<0.05],peripheral blood血CD4+/CD8+cell ratio was(0.7±0.2),significantly higher than(0.6±0.1),P<0.05],serum HBeAg positive rate was 41.3%,significantly lower than(70.4%,P<0.05),and serum HBV pgRNA level was(5.3±0.8)lg copies/mL,significantly lower than(6.5±1.1)lg copies/mL,P<0.05]in non-responders;the multivariate Logistic regression analysis showed that baseline serum HBV DNA loads,serum HBeAg state and serum HBV pgRNA levels were the independent influencing factors for antiviral response in CHB patients receiving nucleos(t)ide analogue treatment(OR=2.793,OR=3.827,OR=4.035,all P<0.05);the ROC analysis demonstrated that the optimal cut-off-value of serum HBV pgRNA level in predicting response of antiviral therapy in CHB patients was 5.89 lg copies/mL,with the AUC of 0.865(95%CI:0.816-0.905),the sensitivity of 74.1%(20/27)and the specificity of 88.8%(71/80).Conclusion Serum HBV pgRNA levels could be assayed in sera of patients with CHB,and it might be used to predict the antiviral response and warrants further clinical investigation.
Keywords:Hepatitis B  Hepatitis B virus pregenomic RNA  Nucleos(t)ide analogues  Response  Prediction
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