传染病信息

目的 探讨急性乙型肝炎（acute viral hepatitis type B, AHB）和不同自然阶段慢性乙型肝炎（chronic hepatitis B, CHB）患者血清病毒标志物和miR-122水平的表达差异及相关性。方法 选取2022年5月至2025年3月期间于空军军医大学第二附属医院就诊的初治AHB患者（AHB组）和CHB患者（CHB组）为研究对象。其中CHB组包括免疫耐受（immune tolerance, IT）期患者35例，免疫清除（immune clearance, IC）期患者48例，低复制（low replication, LR）期患者30例，乙型肝炎e抗原阴性（HBeAg-negative chronic hepatitis B, ENH）期患者41例。采用化学发光法定量血清乙型肝炎表面抗原（hepatitis B surface antigen, HBsAg）滴度，实时荧光定量PCR法检测治疗前血清乙型肝炎病毒（hepatitis B virus, HBV）DNA和miR-122水平。结果 CHB-IT组、CHB-IC组及CHB-ENH组血清HBsAg和HBV DNA水平均显著高于AHB组（均P<0.05）。在CHB各亚组中，CHB-IT组HBsAg和HBV DNA水平最高，显著高于CHB-LR组和CHB-ENH组（均P<0.05）;CHB-IC组和CHB-ENH组HBsAg和HBV DNA水平亦显著高于CHB-LR组（P<0.05）。此外，CHB-IT组、CHB-IC组、CHB-LR组及CHB-ENH组miR-122水平均显著高于AHB组（均P<0.05）。在CHB患者中，CHB-IT组miR-122水平显著高于CHB-LR组和CHB-ENH组（P<0.05）。CHB-IC组和CHBENH组miR-122亦显著高于CHB-LR组（均P<0.05）。Spearman秩相关性分析显示，在AHB或整个CHB患者队列中，miR-122与血清HBsAg、HBV DNA均呈正相关（均P<0.05）。在CHB-IT组、CHB-IC组及CHB-ENH组中，miR-122水平与血清HBsAg、HBV DNA呈正相关性（均P<0.05），而在CHB-LR组中未观察到显著相关性（P>0.05）。此外，miR-122水平与天门冬氨酸氨基转移酶、丙氨酸氨基转移酶水平在CHB-IT组和CHB-IC组中呈负相关（P<0.05）。CHB患者miR-122与肝脏炎症分期和纤维化分期呈负相关（P<0.05）。血清miR-122识别CHB患者严重炎症和严重肝纤维化的曲线下面积分别为0.811(95%CI:0.740～0.869)、0.809(95%CI:0.738～0.868)。结论 血清miR-122水平与HBsAg、HBV DNA水平呈正相关，与病理炎症和纤维化分期呈负相关，提示其与CHB患者病毒复制活跃程度、肝损伤严重程度密切相关。血清miR-122有望作为评估HBV感染肝损伤的新型生物标志物，在确定CHB感染的阶段和病情监测中具有潜在价值。

Objective To explore the expression differences and correlation of serum viral markers and miR-122 levels in patients with acute hepatitis B(AHB) and chronic hepatitis B(CHB) at different natural stages. Methods Patients with initially treated AHB and CHB who attended the Second Affiliated Hospital of Air Force Medical University from May 2022 to March 2025 were enrolled as the study subjects. The CHB group included 35 patients in the immune tolerance(IT) phase, 48 patients in the immune clearance(IC) phase, 30 patients in the low replication(LR) phase, and 41 patients in the HBeAgnegative chronic hepatitis B(ENH) phase. The serum HBsAg titer was quantified by chemiluminescence method, and the serum hepatitis B virus(HBV) DNA and miR-122 levels before treatment were detected by real-time fluorescence quantitative PCR. Results The serum HBsAg and HBV DNA levels in the CHB-IT group, CHB-IC group, and CHB-ENH group were significantly higher than those in the AHB group(all P<0.05). Among the CHB subgroups, the CHB-IT group had the highest HBsAg and HBV DNA levels, which were significantly higher than those in the CHB-LR and CHB-ENH groups(all P<0.05). The HBsAg and HBV DNA levels in the CHB-IC group and CHB-ENH group were also significantly higher than those in the CHB-LR group(P<0.05). In addition, the miR-122 levels in the CHB-IT group, CHB-IC group, CHB-LR group, and CHB-ENH group were significantly higher than those in the AHB group(all P<0.05). Among CHB patients, the miR-122 level in the CHBIT group was significantly higher than those in the CHB-LR and CHB-ENH groups(P<0.05). The miR-122 level in the CHB-IC group and CHB-ENH group was also significantly higher than that in the CHB-LR group(all P<0.05). Spearman rank correlation analysis showed that miR-122 was positively correlated with serum HBsAg and HBV DNA in the AHB or the entire CHB patient cohort(all P<0.05). Stratified analysis of CHB patients by different natural phases revealed that the miR-122 level was positively correlated with serum HBsAg and HBV DNA in the CHB-IT group, CHB-IC group, and CHB-ENH group(all P<0.05), while no significant correlation was observed in the CHB-LR group(P>0.05). Moreover, the miR-122 level was negatively correlated with aspartate aminotransferase(AST) and alanine aminotransferase(ALT) levels in the CHB-IT group and CHB-IC group(P<0.05). Spearman rank correlation analysis showed that miR-122 was negatively correlated with liver inflammation stage and fibrosis stage in CHB patients(P<0.05). ROC curve analysis showed that the area under the curve of serum miR-122 for identifying severe inflammation and severe liver fibrosis in CHB patients could reached 0.811(95%CI: 0.740-0.869) and 0.809(95%CI: 0.738-0.868), respectively. Conclusion Serum miR-122 levels are positively correlated with the levels of HBsAg and HBV DNA, and negatively correlated with the pathological inflammation and fibrosis stages, suggesting that it is closely associated with the degree of viral replication activity and the severity of liver injury in CHB patients. Serum miR-122 is expected to serve as a novel biomarker for evaluating liver injury in HBV infection, with potential value in determining the stage of CHB infection and monitoring disease progression.