目的 探讨血清外泌体微RNA（miRNA）与慢性乙型肝炎（CHB）患者肝组织炎症损伤及组织学转归之间的关联。 方法 从6例健康者及6例CHB患者中采集外周血清，经尺寸洗脱色谱法提取外泌体。通过小RNA测序及转录组学分析，识别与肝组织炎症损伤和肝纤维化程度相关的血清外泌体miRNA，分别在脂多糖/D-氨基半乳糖诱导急性肝损伤小鼠模型、四氯化碳诱导肝纤维化大鼠模型及84例具有治疗前后两次肝活检病理评估的CHB患者中进行实时荧光定量PCR验证。正态分布的计量资料两组间比较采用成组t检验；多组间比较采用方差分析，进一步两两比较采用Tukey检验。非正态分布的计量资料两组间比较采用Mann-Whitney U检验；多组间比较采用Kruskal-Wallis H检验，进一步两两比较采用Dunn检验。计数资料组间比较采用χ²检验或Fisher精确检验。采用单因素和多因素Logistic回归分析影响因素。 结果 血清外泌体miR-122-5p在CHB患者中异常表达，并在伴有融合性坏死及晚期肝纤维化患者中表达均下调。在急性肝损伤小鼠模型和肝纤维化大鼠模型中，与对照组相比，模型组肝脏miR-122-5p的表达水平均显著降低（P值分别为0.048、0.014）；与轻度肝损伤相比，伴有重度融合性坏死和晚期纤维化的肝组织中miR-122-5p的表达水平进一步显著下降（P值均<0.05）。在84例CHB患者中，伴肝组织重度融合性坏死或晚期肝纤维化患者，其血清外泌体miR-122-5p的表达显著低于轻度肝损伤患者（P值分别为<0.001、0.003）。多因素Logistic回归分析显示，miR-122-5p表达水平是融合性坏死（OR=0.001，95%CI：0.000～0.037，P=0.005）和肝纤维化程度（OR=0.568，95%CI：0.331～0.856，P=0.019）的独立影响因素。相较于miR-122-5p低表达患者，治疗前高水平表达患者在接受抗病毒治疗72周后其肝纤维化的逆转率更高（64.3% vs 38.1%，P=0.029）。 结论 CHB患者血清外泌体miR-122-5p与肝脏融合性坏死和纤维化进展密切相关，其表达水平降低可能加重肝脏融合性坏死，促进纤维化进展，并可能影响CHB患者接受抗病毒治疗后的肝组织学转归。

Objective To investigate the association of serum exosomal microRNAs （miRNAs） with hepatic inflammatory injury and histological outcomes in patients with chronic hepatitis B （CHB）. Methods Peripheral serum samples were collected from six healthy adults and six patients with CHB，and size exclusion chromatography was used to extract exosomes. Small RNA sequencing and transcriptomic analysis were used to identify the serum exosomal miRNAs associated with liver inflammatory injury and fibrosis，and quantitative real-time PCR was used for validation in a mouse model of acute liver injury induced by lipopolysaccharide/D-galactosamine，a rat model of liver fibrosis induced by carbon tetrachloride，and 84 CHB patients undergoing liver biopsy twice before and after treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； an analysis of variance was used for comparison between multiple groups，and the Tukey test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups，and the Dunn test was used for further comparison between two groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to investigate influencing factors. Results Abnormal expression of serum exosomal miR-122-5p was observed in patients with CHB，and it was downregulated in patients with confluent necrosis and advanced fibrosis. In the mouse model of acute liver injury and the rat model of liver fibrosis，compared with the control group，the model group had a significant reduction in the expression level of miR-122-5p in the liver （P=0.048 and 0.014），and compared with the patients with mild liver injury，the patients with severe confluent necrosis and advanced fibrosis showed a significant reduction in the expression level of miR-122-5p in liver tissue （P<0.05）. Among the 84 CHB patients，the patients with severe hepatic confluent necrosis or advanced liver fibrosis had a significantly lower expression level of serum exosomal miR-122-5p than those with mild liver injury （P<0.001 and P=0.003）. The multivariate Logistic regression analysis showed that the expression level of miR-122-5p was an independent influencing factor for confluent necrosis （odds ratio ［OR］=0.001，95% confidence interval ［CI］：0.000‍ ‍—‍ ‍0.037，P=0.005） and liver fibrosis degree （OR=0.568，95%CI：0.331‍ ‍—‍ ‍0.856，P=0.019）. In addition，compared with the patients with low expression of miR-122-5p，the patients with high expression of miR-122-5p before treatment had a significantly higher reversal rate of liver fibrosis after 72 weeks of antiviral therapy （64.3% vs 38.1%，P=0.029）. Conclusion Serum exosomal miR-122-5p in CHB patients is closely associated with the progression of hepatic confluent necrosis and fibrosis，and the reduction in the expression level of miR-122-5p may aggravate hepatic confluent necrosis，promote the progression of fibrosis，and affect the histological outcome of CHB patients after antiviral therapy.