Objective: To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy. Methods: 100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ (2) test and Fisher's exact test were used to compare categorical variables. Results: HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks (n = 54) during subsequent treatment compared to those who did not (n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients (P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy (r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion: HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.
目的： 探究新型临床标志物血清乙型肝炎病毒（HBV）前基因组RNA（pgRNA）水平在长期抗病毒治疗慢性乙型肝炎（CHB）患者中的的临床变化特点。 方法： 纳入在北京大学第一医院就诊的100例核苷（酸）类似物（NAs）初治CHB患者，分别检测患者随访期间的丙氨酸转氨酶（ALT）、HBV DNA、乙型肝炎e抗原（HBeAg）、乙型肝炎表面抗原（HBsAg）水平，并使用Taqman法实时定量PCR检测血清HBV pgRNA水平。连续变量采用独立样本t检验和Mann-Whitney U检验进行组间比较，分类变量采用Pearson χ(2)检验和Fisher精确检验进行组间比较。 结果： 48周时发生病毒学应答者（n = 54）在后续治疗中的HBV pgRNA下降水平显著高于未发生病毒学应答者（n = 46）；HBeAg阳性患者的HBV pgRNA下降水平低于HBeAg阴性者；P < 0.05或P < 0.01。抗病毒治疗后，基线期HBV DNA水平更高、HBeAg阳性患者HBV pgRNA水平更高，基线期HBV pgRNA水平不同的患者抗病毒治疗后的HBV pgRNA水平差异无统计学意义。血清HBV pgRNA与HBsAg在基线期无相关性，而在长期抗病毒治疗后出现相关性，抗病毒治疗第5年、第9年HBV pgRNA与HBsAg存在弱相关性（分别为r = 0.262，P = 0.031；r = 0.288，P = 0.008）。 结论： 在CHB长期抗病毒治疗过程中，HBV活性较高CHB患者的HBV pgRNA水平更高。.
Keywords: Chronic hepatitis B; Hepatitis B virus; pgRNA.