【摘要】 目的 探讨慢性乙型肝炎（CHB）患者接受核苷（酸）类似物（NAs）治疗期间，在乙型肝炎病毒（HBV）DNA阴转，血清前基因组RNA(pgRNA)的动态变化对疗效评估的临床意义。方法 （1）2015年11月至2016年8月62例研究对象均来自广西医科大学第一附属医院感染性疾病科抗病毒治疗的CHB患者队列，接受NAs治疗均获得HBV DNA完全病毒学应答且维持应答时间>3年。（2）采用荧光定量PCR检测基线、HBV DNA首次应答和维持应答1、2、3年各个时间点血清pgRNA载量。（3）分析基线HBV DNA和pgRNA相关性、治疗期间血清pgRNA变化、血清pgRNA累计阴转率以及影响因素；分析观察终点pgRNA阳性率与治疗后各时间点pgRNA水平：EASL停药标准的关系。结果 （1）基线HBV DNA和pgRNA呈中度正相关（r=0.789,P<0.01）。（2）治疗期间，血清pgRNA载量逐渐下降（P<0.01）;HBV DNA首次应答和维持应答1、2、3年时的血清pgRNA累计阴转率分别为：22.6%(14/62)、37.1%(23/62)、37.1%(23/62)、41.9%(26/62)。（3）治疗期间影响血清pgRNA变化的亚组分析显示：治疗后各时间点pgRNA水平：基线HBV DNA载量>6(lg copies/mL)组高于基线HBV DNA载量≤6(lg copies/mL)组（P=0.001）；基线HBeAg阳性组高于基线HBeAg阴性组（P<0.001）;HBV DNA病毒学应答时间>6个月高于HBV DNA病毒学应答时间≤6个月组（P=0.003）。（4）观察终点时，达到和未达到欧洲肝脏研究学会（EASL）指南停药标准患者的血清pgRNA阳性率为48.5%对68.9%(P=0.103)。结论 （1）CHB患者长期有效NAs治疗，可持续获得血清pgRNA消减；（2）动态定量检测血清pgRNA，有助于判断NAs抗病毒治疗的疗效，尤其在血清HBV DNA不可检测之后肝内共价闭合环状DNA耗竭状态；（3）血清pgRNA可以作为评估安全停药的指标补充。更多还原

【Abstract】 Objective To explore the clinical significance of dynamic changes of serum pgRNA level in evaluating therapeutic effect when serum HBV DNA is undetectable in chronic hepatitis B(CHB)with nucleos(t)ide analogues(NAs)therapy. Methods(1)Sixty-two CHB patients,who received NAs treatment and whose HBV DNA obtained completely over 3 years from No. 2015 to Aug 2016 were selected from the antiviral therapy cohort from the Department of Infectious Diseases,the First Affiliated Hospital of Guangxi Medical University(.2)Real-time fluorescent quantitative polymerase chain reaction(PCR) was used to detect the serum pgRNA at five follow-up points: treatment baseline,first response serum HBV DNA,and1,2,3 years of maintaining response.(3)We analyzed the correlation between baseline HBV DNA and pgRNA,serum pgRNA kinetics,cumulative negative rate of serum pgRNA,and affecting factors during treatment;the relationship between the positive rate of pgRNA at the end of observation and EASL withdrawal criteria. Results(1)There was a moderate correlation between baseline HBV DNA and pgRNA(r = 0.789,P<0.01).(2)Serum pgRNA level gradually decreased during NAs treatment(P<0.01); the cumulative negative rates of serum pgRNA at the point of HBV DNA first response and maintained response for 1,2 and 3 years were: 22.6%(14/62),37.1%(23/62),37.1%(23/62),and 41.9%(26/62),respectively(.3)Subgroup analysis that affected the changes of serum pgRNA showed serum pgRNA level at each time point after treatment: group with baseline HBVDNA load >6(lg copies/ml) was higher than group with baseline HBV DNA load ≤6(lg copies/ml)(P= 0.001),group with baseline HBeAg positive was higher than group with baseline HBeAg negative(P <0.001),and group with HBVDNA virological response time >6 months was higher than group with HBV DNA virological response time ≤6 months(P =0.003)(.4)At the end of observation,serum pgRNA positive rate of patients who reached and did not reach the guidelines cessation criteria of EASL was 48.5% and 68.90%(P=0.103).Conclusion(1) CHB patients receiving long-term effective NAs treatment can obtain continuous serum pgRNA reduction.(2)Dynamic quantitative detection of serum pgRNA is helpful to evaluate the efficacy of NAs treatment,especially to assess the cccDNA transcriptional status when serum HBV DNA is undetectable.(3)Serum pgRNA can be used as an index supplement to evaluate safe NAs withdrawal.更多还原