经核苷(酸)类似物治疗的慢性乙肝患者血清乙肝病毒前基因组RNA的临床意义

Clinical significance of hepatitis B virus pregenomic RNA in chronic hepatitis B patients treated with nucleoside(acid) analogues

目的分析经核苷(酸)类似物(NAs)抗病毒治疗后血清HBV DNA<20 IU/ml的慢性乙型肝炎(CHB)患者血清HBV前基因组RNA(pgRNA)的表达及与HBV表面抗原(HBsAg)的相关性,探讨HBV pgRNA检测的临床意义。方法根据接受NAs单药抗病毒治疗时间将185例CHB患者分为48周组(53例)、144周组(61例)及240周组(71例),收集其一般资料和治疗后的实验室检查结果[ALT、AST、HBsAg、HBV pgRNA检出率及其水平、HBV e抗原(HBeAg)表达情况]并分组进行比较。根据治疗后HBeAg表达情况将185例患者分为HBeAg阳性组(53例)和HBeAg阴性组(132例),比较两组患者血清HBV pgRNA检出率和水平。采用Spearman相关分析评估血清HBV pgRNA与HBsAg的相关性。结果240周组患者HBsAg水平低于48周组;144周组和240周组患者HBV pgRNA检出率均低于48周组,144周组和240周组患者HBV pgRNA水平均低于48周组,240周组患者HBV pgRNA水平低于144周组;HBeAg阳性组患者血清HBV pgRNA检出率和水平均显著高于HBeAg阴性组(P<0.05)。Spearman相关分析结果显示,经NAs治疗的CHB患者血清HBV pgRNA水平与HBsAg水平呈正相关,HBeAg阳性患者HBV pgRNA水平与HBsAg水平呈正相关(P<0.01)。结论血清HBV pgRNA检测简便无创,在HBV DNA阴转后,作为临床持续监测共价闭合环状DNA(cccDNA)水平的血清学标志物具有广阔的应用前景。

Objective To analyze the expression of serum HBV pregenomic RNA(pgRNA)and its correlation with HBV surface antigen(HBsAg)in chronic hepatitis B(CHB)patients with serum HBV DNA<20 IU/ml after antiviral treatment with nucleoside(acid)analogue(NAs),investigate the clinical significance of HBV pgRNA detection.Methods According to the time of NAs monotherapy,185 patients with CHB were divided into 48 weeks group(53 cases),144 weeks group(61 cases)and 240 weeks group(71 cases).The general data and laboratory test indicators after treatment[ALT,AST,HBsAg,HBV pgRNA detection rate and their levels,HBV e antigen(HBeAg)expression]were collected and grouped for comparison.According to the expression of HBeAg after treatment,185 patients were divided into HBeAg positive group(53 cases)and HBeAg negative group(132 cases).The detection rate and level of serum HBV pgRNA were compared between the two groups.Spearman correlation analysis was used to evaluate the correlation between serum HBV pgRNA and HBsAg.Results The level of HBsAg in 240 weeks group was lower than that in 48 weeks group;The detection rate of HBV pgRNA in 144 weeks group and 240 weeks group were lower than that in 48 weeks group,the level of HBV pgRNA in 144 weeks group and 240 weeks group were lower than that in 48 weeks group,and the level of HBV pgRNA in 240 weeks group was lower than that in 144 weeks group;The detection rate and level of serum HBV pgRNA in HBeAg positive group were significantly higher than those in HBeAg negative group(P<0.05).Spearman correlation analysis showed that serum HBV pgRNA level was positively correlated with HBsAg level in CHB patients treated with NAs,and HBsAg level was positively correlated with HBV pgRNA level in HBeAg positive patients(P<0.01).Conclusion Serum HBV pgRNA detection is simple and non-invasive.After HBV DNA turns negative,it has a broad application prospect as a serological markers for clinical continuous monitoring of cccDNA levels.