抗病毒治疗慢性乙型肝炎患者血清外泌体HBV-miR-3动态变化与病毒学指标的关系

Dynamic changes of serum exosomal HBV-miR-3 in patients with chronic hepatitis B treated with antiviral therapy and its relationship with virological indicators

目的探讨抗病毒治疗慢性乙型肝炎(CHB)患者血清外泌体HBV-miR-3动态变化与病毒学指标的关系。方法选取2020年6月至2021年6月收治的116例CHB患者,均接受抗病毒治疗12个月,比较发生病毒学应答组(VR+组)和未发生病毒学应答组(VR-组)一般资料及接受抗病毒治疗前后病毒学指标和外泌体HBV-miR-3的动态变化。采用Pearson相关分析外泌体HBV-miR-3水平与病毒学指标的关系,采用受试者工作特征曲线分析外泌体HBV-miR-3水平对病毒学应答的预测效能。结果经12个月抗病毒治疗后,VR+组54例,VR-组62例,病毒学应答率为46.55%;VR+组ALT水平高于VR-组,而HBsAg、HBV DNA和外泌体HBV-miR-3水平低于VR-组(P<0.05);VR+组HBsAg、HBV DNA和外泌体HBV-miR-3水平在接受抗病毒治疗后明显下降,而VR-组虽有下降但变化不明显,且一直高于VR+组(P<0.05);血清外泌体HBV-miR-3水平与ALT无明显相关性(r=0.049,P=0.241),与HBV DNA和HBsAg呈正相关(r=0.314、0.809,P<0.05)。治疗3个月时,以4.52lg拷贝/mL为最佳界值的AUC最大为0.857(95%CI:0.716~0.962),敏感度和特异度最高,分别为82.70%和78.10%。结论CHB患者血清外泌体HBV-miR-3水平随着抗病毒治疗时间的延长而下降,与病毒学指标HBV DNA和HBsAg呈正相关,抗病毒治疗3个月时HBV-miR-3的临界值可作为预测CHB患者抗病毒治疗12个月的病毒学应答的指标。

Objective To investigate the dynamic changes of serum exosomal HBV-miR-3 in patients with chronic hepatitis B(CHB)treated with antiviral therapy and its relationship with virological indicators.Methods A total of 116 patients with CHB who were admitted from June 2020 to June 2021 were selected,all received antiviral therapy for 12 months.The patients were divided into a virological response group(VR+group)and a non-viral response group(VR-group)according to their levels of HBV DNA after treatment.The general data and dynamic changes of virological parameters and serum exosomal HBV-miR-3 before and after antiviral therapy were compared between VR+and VR-groups.The relationship between exosomal HBV-miR-3 levels and virological indicators was investigated by Pearson correlation analysis,and the predictive efficacy of exosomal HBV-miR-3 levels on virological response was analyzed by receiver operating characteristic(ROC)curve analysis.Results After 12 months of antiviral treatment,54 cases had virological response(VR+group)and 62 cases did not obtain viral response(VR-group).The virological response rate was 46.55%.The level of ALT in the VR+group was higher than that in the VR-group,while the HBsAg concentration,HBV DNA load and exosomal HBV-miR-3 levels were lower than those in the VR-group(P<0.05).The HBsAg concentration,HBV DNA load and exosomal HBV-miR-3 level in the VR+group decreased significantly after receiving antiviral treatment,while the VR-group decreased but did not change significantly,and was always higher than the VR+group(P<0.05).Serum exosomal HBV-miR-3 levels were not significantly correlated with ALT(r=0.049,P=0.241),but were positively correlated with HBV DNA and HBsAg(r=0.314,0.809,P<0.05).The ROC curve results showed that at 3 months of treatment,the AUC(0.857)(95%CI:0.716-0.962)with 4.52 lg copies/ml as the optimal cutoff value was the largest,and the sensitivity and specificity were the highest,which were 82.70%and 82.70%,respectively.Conclusion The level of serum exosomal HBV-miR-3 in CHB patients decreased with the prolongation of antiviral treatment time,and was positively correlated with virological indicators of HBV DNA and HBsAg,and HBV-miR-3≤4.52 lg copies/ml at 3 months of antiviral therapy can be used as an indicator to predict the virological response of CHB patients with 12 months of antiviral therapy.