血清miR-25-3p、miR-425-5p对持续ALT正常慢性乙型肝炎肝脏慢性炎症的诊断价值

作者：王赟1  赵成进1  张瑜2

单位：1. 青海省第四人民医院 急诊科 青海 西宁 810000 2. 青海省第四人民医院 肝病科 青海 西宁 810000

关键词：肝炎 乙型 慢性 丙氨酸氨基转移酶 miR-25-3p miR-425-5p 肝脏炎症

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出版年,卷(期):页码：2025,17(4):57-62

摘要：

摘要：目的 探究血清微小RNA-25-3p（microRNA-25-3p，miR-25-3p）、微小 RNA-425-5p（microRNA-425-5p，miR-425-5p）对持续丙氨酸氨基转移酶（alanine aminotransferase，ALT）正常的慢性乙型肝炎（chronic hepatitis B，CHB）患者肝脏慢性 炎症的诊断价值。方法 以2021年3月1日至2024年3月31日青海省第四人民医院收治的118例 CHB患者为研究对象，根据肝组织活检对患者肝脏炎症活动度分级（G），其中G0/G1 组49例，G2组49例，G3/G4组20例。收集所有患者ALT、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）、总胆红素（total bilirubin，TBil）、白蛋白（albumin，ALB） 水平。采用定量逆转录聚合酶链反应（quantitative reverse transcription polymerase chain reaction，qRT-PCR）检测血清miR-25-3p、miR-425-5p水平。采用Spearman相关性分析 miR-25-3p、miR-425-5p水平与肝脏炎症活动度的相关性，采用Pearson相关性分析miR-25- 3p、miR-425-5p水平与AST、TBil、ALB水平的相关性，采用受试者工作特征（receiver operating characteristic，ROC）曲线评价血清miR-25-3p、miR-425-5p水平预测CHB患者肝 脏炎症活动度G ≥ 2的价值。结果 与G0/G1组相比，G2组、G3/G4组患者AST [（35.19 ± 7.48）U/L比（51.27 ± 10.91）U/L比（28.19 ± 7.19）U/L]、TBil [（16.43 ± 3.42）µmol/L比 （23.73 ± 5.26）µmol/L比（10.18 ± 2.18）µmol/L] 及miR-25-3p相对表达量（2.43 ± 0.67 比3.49 ± 0.74比1.02 ± 0.31）均显著升高，ALB [（39.78 ± 8.35）g/L比（35.06 ± 7.48）g/L 比（45.68 ± 9.98）g/L] 和miR-425-5p相对表达量（0.64 ± 0.22比0.42 ± 0.13比1.04 ± 0.32）均显著降低（P均＜ 0.05）。与G2组相比，G3/G4组患者AST、TBil及miR-25-3p 相对表达量均显著升高，ALB和miR-425-5p相对表达量均显著降低（P均＜ 0.05）。 Spearman相关性分析表明，患者血清miR-25-3p水平与肝脏炎症活动度呈正相关（rs = 0.576，P = 0.026）；血清miR-425-5p水平与肝脏炎症活动度呈负相关（rs = －0.458， P = 0.017）；Pearson相关性分析表明，miR-25-3p与AST和TBil呈正相关（r = 0.516， P ＜ 0.001；r = 0.476，P = 0.008），与ALB呈负相关（r = －0.473，P = 0.009）；miR- 425-5p与AST和TBil呈负相关（r = －0.506，P ＜ 0.001；r = －0.462，P = 0.011），与 ALB呈正相关（r = 0.481，P = 0.004）。miR-25-3p + miR-425-5p预测CHB患者肝脏炎 症活动度G ≥ 2的ROC曲线下面积（0.923）显著大于miR-25-3p（0.859）、miR-425-5p （0.836）单独预测（Z = 2.305，P = 0.021；Z = 2.786，P = 0.005）。结论 ALT持续正 常的CHB患者中部分存在严重的肝脏慢性炎症，血清miR-25-3p、miR-425-5p水平对评 估患者肝脏慢性炎症具有一定价值。

Abstract: Objective To investigate the value of serum microRNA-25-3p (miR-25-3p) and microRNA-425-5p (miR-425-5p) on the diagnosis of chronic inflammation of liver in chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (ALT). Methods A total of 118 patients with CHB admitted to The Fourth People’s Hospital of Qinghai Province from March 1st, 2021 to March 31st, 2024 were selected as the research objects. According to the grading of liver inflammation activity (G) based on liver biopsy, there were 49 cases in G0/G1 group, 49 cases in G2 group and 20 cases in G3/G4 group. The levels of ALT, aspartate aminotransferase (AST), total bilirubin (TBil) and albumin (ALB) of the patients were collected. The serum levels of miR-25-3p and miR-425-5p were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Spearman correlation analysis was used to analyze the correlations between the levels of miR-25-3p, miR-425-5p and the liver inflammation activity. Pearson correlation analysis was used to analyze the correlations between the levels of miR-25-3p, miR-425-5p and levels of AST, TBil and ALB. Receiver operating characteristic (ROC) curves was used to evaluate the value of serum miR-25-3p and miR-425-5p levels on predicting liver inflammation activity grade G ≥ 2 in patients with chronic hepatitis B (CHB). Results Compared with patients in G0/G1 group, patients in G2 group and G3/G4 group showed significantly higher levels of AST [(35.19 ± 7.48) U/L vs. (51.27 ± 10.91) U/L vs. (28.19 ± 7.19) U/L], TBil [(16.43 ± 3.42) µmol/L vs. (23.73 ± 5.26) µmol/L vs. (10.18 ± 2.18) µmol/L] and relative expression of miR-25-3p (2.43 ± 0.67 vs. 3.49 ± 0.74 vs. 1.02 ± 0.31). In contrast, the levels of ALB [(39.78 ± 8.35) g/L vs. (35.06 ± 7.48) g/L vs. (45.68 ± 9.98) g/L] and relative expression of miR-425-5p (0.64 ± 0.22 vs. 0.42 ± 0.13 vs. 1.04 ± 0.32) were significantly lower (all P ＜ 0.05). Compared with patients in G2 group, patients in G3/G4 group exhibited significantly higher levels of AST, TBil and relative expression of miR-25-3p, while ALB levels and relative expression of miR-425-5p were significantly lower (all P ＜ 0.05). Spearman correlation analysis showed that serum miR-25-3p level was positively correlated with liver inflammation activity (rs = 0.576, P = 0.026) and miR-425-5p level was negatively correlated with liver inflammation activity (rs = －0.458, P = 0.017). Pearson analysis showed that miR-25-3p level was positively correlated with AST and TBil (r = 0.516, P ＜ 0.001; r = 0.476, P = 0.008), and negatively correlated with ALB (r = －0.473, P = 0.009); miR-425-5p level was negatively correlated with AST and TBil (r = －0.506, P ＜ 0.001; r = －0.462, P = 0.011), and positively correlated with ALB (r = 0.481, P = 0.004). The area under ROC curve of miR-25-3p + miR-425-5p (0.923) for predicting liver inflammation activity grade G ≥ 2 in CHB patients was significantly larger than that predicted by miR-25-3p alone (0.859) or miR-425-5p alone (0.836) (Z = 2.305, P = 0.021; Z = 2.786, P = 0.005). Conclusions Some CHB patients with persistently normal ALT levels have severe chronic liver inflammation. Serum levels of miR-25-3p and miR-425-5p have certain value on evaluating chronic liver inflammation in CHB patients.

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