HBV RNA is a novel serum biomarker that reflects intrahepatic HBV covalently closed circular DNA (cccDNA) transcription activity. Serum HBV RNA levels among treatment-naïve adults during the natural history of chronic hepatitis B (CHB) and distinct liver histopathology statuses remain elusive. In our study, we include a total of 411 treatment-naïve CHB patients, among which 43 patients were HBeAg-positive immune-tolerant [IT(e⁺)], 84 patients were HBeAg-positive immune active [IA(e⁺)], 65 patients in HBeAg-negative immune active phases [IA(e⁻)], 149 patients were HBeAg-negative inactive phases [IC(e⁻)], and 70 patients were in Gray Zone (GZ). HBV RNA was measured in this cohort and its potential correlation with traditional serological markers and liver histopathology were analyzed. Our data showed that HBV RNA was strongly correlated with HBV DNA, HBeAg, HBsAg and ALT. Further subgroup analysis revealed a close correlation between HBV RNA and HBV DNA in patients in the IA (e⁺) and IA (e⁻) phases, but neither in IT(e⁺) nor IC(e⁻) phase. HBV RNA levels were consistently increased with the advanced degrees of hepatic inflammation, but not hepatic fibrosis. Of note, HBV RNA from HBeAg-positive patients negatively correlated with liver fibrosis, whereas HBV RNA from HBeAg-negative patients was weakly associated with liver inflammation. To sum up, serum HBV RNA shows a distinct profile among CHB patients in different immune statuses and hepatic histopathology stages/grades. Simultaneous testing of HBV RNA and traditional indicators might provide a comprehensive clinical assessment of CHB patients.

HBV RNA 是一种新型血清生物标志物，反映肝内 HBV 共价闭合环状 DNA (cccDNA) 转录活性。慢性乙型肝炎 (CHB) 自然史期间未接受治疗的成年人的血清 HBV RNA 水平和不同的肝脏组织病理学状态仍然难以捉摸。在我们的研究中，我们总共纳入了 411 名初治 CHB 患者，其中 43 名患者为 HBeAg 阳性免疫耐受 [IT(e + ⁾ ]，84 名患者为 HBeAg 阳性免疫活跃 [IA(e ⁺ )]其中，65 名患者处于 HBeAg 阴性免疫活跃期 [IA(e ⁻ )]，149 名患者处于 HBeAg 阴性非活跃期 [IC(e ⁻ )]，70 名患者处于灰色区 (GZ)。在该队列中测量了 HBV RNA，并分析了其与传统血清学标志物和肝脏组织病理学的潜在相关性。我们的数据显示，HBV RNA 与 HBV DNA、HBeAg、HBsAg 和 ALT 密切相关。^{进一步的亚组分析显示，IA (e +} ) 和 IA (e ⁻ ) 期患者的 HBV RNA 和 HBV DNA 之间存在密切相关性，但 IT(e ^{+ ) 期和 IC(e −} ) 期患者的 HBV RNA 和 HBV DNA之间没有密切相关性。HBV RNA 水平随着肝脏炎症程度的加深而持续升高，但肝纤维化则不然。值得注意的是，HBeAg 阳性患者的 HBV RNA 与肝纤维化呈负相关，而 HBeAg 阴性患者的 HBV RNA 与肝脏炎症微弱相关。综上所述，不同免疫状态和肝组织病理学阶段/等级的慢性乙型肝炎患者的血清 HBV RNA 显示出不同的特征。同时检测 HBV RNA 和传统指标可能会为 CHB 患者提供全面的临床评估。