Objective: To study the relationship between serum HBV pgRNA and antigen status in patients with chronic hepatitis B treated with long-term nucleotide analogues, and to elucidate the reason and possible mechanism of high relapse rate in antiviral therapy of nucleotide analogues in chronic hepatitis B. Methods: 94 patients with chronic hepatitis B who had been treated with long-term antiviral therapy with nucleotide analogues (more than 2 years) were divided into 5 groups according to their HBeAg and HBsAg levels: e antigen positive group(group1), e antigen negative and HBsAg > 1 500 IU/L group(group2), e antigen negative and 100 IU/L< HBsAg < 1 500 IU/L group(group3), e antigen negative and HBsAg < 100 IU/L group(group4), e antigen negative and HBsAg negative group(group5). The level and detection rate of HBVpgRNA in different antigen states groups were analyzed and compared. In addition, in order to exclude the influence of other factors on the results of this study. The study was divided into groups according to age, gender and treatment time. Results: The detection rate of HBVpgRNA was 95.0% in patients with e antigen positive, while 43.2% in patients with e antigen seroconversion, which was significantly lower than that in patients with e antigen positive (P < 0.05). The detection rate of serum HBVpgRNA was 95.0% in e antigen positive group, 75.0% in group 2, 65.0% in e antigen negative with group 3, 15.0% in group 4 and 0% in group 5. Among them, group 1, group 2 and group 3 was significantly higher than that in group 4 and group 5. There was significant difference between the two groups (P < 0.05). However, there was no difference in the positive rate of serum HBV pgRNA among group 1, group 2 and group 3 (P > 0.05). Similarly, there was no difference in the positive rate of serum HBV pgRNA between group 4 and group 5 (P > 0.05). Moreover, the detection rate of serum HBV pgRNA was not correlated with age, gender and treatment time of nucleotide analogues (P > 0.05). Conclusion: There is a significant correlation between the serological antigen status and the presence of HBV pgRNA in chronic hepatitis B after long-term treatment of nucleotide analogues. The persistence of HBV pgRNA is closely related to the low seroconversion rate of e antigen and the high level of HBsAg. HBV pgRNA can be used as one of the biomarkers to judge the transcription activity and replication status of HBV cccDNA in liver.
目的： 研究长期核苷酸类似物治疗的慢性乙型肝炎患者血清乙型肝炎病毒前基因组RNA（HBV pgRNA）与抗原状态变化的相关性，阐明慢性乙型肝炎长期核苷酸类似物抗病毒治疗，达到HBeAg血清转换后停药复发率高的原因和可能的机制。 方法： 选择长期口服核苷酸类似物抗病毒治疗（2年以上）的慢性乙型肝炎患者94例，在其血清HBV DNA低于检测下限（< 20 IU/ml）的基础上，根据其HBeAg和HBsAg水平分为5组：HBeAg阳性组(组1)、HBeAg阴性且HBsAg > 1 500 IU/L组(组2)、HBeAg阴性且100 IU/L < HBsAg < 1 500 IU/L组（组3）、HBeAg阴性且HBsAg < 100 IU/L组（组4）及HBeAg阴性同时HBsAg阴性组（组5）。分析比较不同抗原状态下HBV pgRNA的水平及检出率。此外，为了排除其他因素对本研究结果的影响。研究分别按照年龄、性别和服药治疗时间分组。按资料分别用t检验、Mann-Whitney U检验、Kruskal-Wallis H检验或线性回归相关性分析进行统计学分析。 结果： HBeAg阳性患者（组1）血清HBV pgRNA检出率为95.0%；而HBeAg阴性患者则为43.2%，明显低于HBeAg阳性者，差异有统计学意义（P < 0.05）。血清HBV pgRNA检出率在HBeAg阴性患者中，组2为75.0%；组3为65.0%；组4为15.0%及组5为0。其中，组1、组2及组3的血清HBV pgRNA检出率明显高于组4和组5，差异有统计学意义（P值均< 0.05）。然而，统计学分析发现：组1、组2和组3之间血清HBV pgRNA检出率差异无统计学意义（P > 0.05）。组4和组5之间的血清HBV pgRNA检出率比较，差异无统计学意义（P > 0.05）。而且，血清HBV pgRNA检出率与患者的年龄、性别及核苷酸类似物治疗时间无相关性（P > 0.05）。 结论： 慢性乙型肝炎长期核苷酸类似物抗病毒治疗后的血清学抗原状态可能与血清HBV pgRNA的存在有关。HBV pgRNA的持续存在也可能是HBeAg血清转换率低及HBsAg持续高水平的原因。.
Keywords: Chronic hepatitis B; HBV pregenomic RNA; Hepatitis B e antigen; Hepatitis B s antigen; Nucleotide analogues.