乙型病毒肝炎及晚期肝纤维化患者血清中miR-223的表达及临床意义

The expression and clinical significance of miR-223 in serum from patients with hepatitis B and advanced liver fibrosis

目的探讨微小RNA-223(miR-223)在乙型病毒肝炎及晚期肝纤维化患者血清中的表达及临床意义。方法选择2018年1月-2021年4月在本院治疗的乙肝患者168例为研究对象,根据病理穿刺检查分期:S0-1期58例,S2期42例,S3期33例,S4期35例。另选择本院体检健康者50例作为对照组。qRT-PCR检测受试者血清miR-223的表达情况,Pearson法分析血清miR-223与生化指标的相关性,Spearman法分析血清miR-223与肝纤维化分期的相关性,ROC曲线分析血清miR-223对乙肝患者肝纤维化程度的诊断价值。结果 S0-1、S2、S3、S4期患者的年龄、性别差异均无统计学意义(均P>0.05),4组患者ALT、AST、PLT、GGT、ALB、HBV-DNA、FIB-4指数和APRI指数差异均有统计学意义(均P<0.01);S0-1、S2、S3、S4期患者血清miR-223分别为1.37±0.15、2.05±0.21、2.84±0.36、3.52±0.43,与对照组比较显著升高(P<0.01);S0-1、S2、S3、S4期患者之间血清miR-223水平差异有统计学意义(P<0.05),且患者肝纤维化分期越高,血清miR-223水平越高;Spearman相关性分析显示,乙肝患者血清miR-223水平与肝纤维化分期呈正相关(r=0.564,P<0.01);Pearson相关性分析显示,乙肝患者血清miR-223与APRI、Fib-4呈正相关(r值分别为0.525和0.621,均P<0.01);ROC曲线分析显示,血清miR-223对不同肝纤维化程度均有一定诊断价值,尤其是晚期纤维化和肝硬化诊断效能更佳,其曲线下面积、敏感度和特异度均高于对S0-2期的诊断。结论乙肝患者血清miR-223水平升高,且与肝纤维化程度有关,可用于评估乙肝患者纤维化进展,尤其是晚期纤维化。

Objective To investigate the expression and clinical significance of microRNA-223(miR-223) in serum from patients with hepatitis B and advanced liver fibrosis. Methods Subjects were a total of 168 patients with hepatitis B who were seen at this Hospital from January 2018 to April 2021. A liver puncture was performed for pathology: liber fibrosis was stage S0-1 in 58 patients, stage S2 in 42, stage S3 in 33, and S4 in 35. In addition, 50 healthy patients served as the control group. qRT-PCR was used to measure the expression of serum miR-223, the Pearson method was used to analyze the correlation between serum miR-223 and biochemical indicators, the Spearman method was used to analyze the correlation between serum miR-223 and liver fibrosis stages, and the ROC curve was used to analyze the diagnostic value of serum miR-223 at identifying different degrees of liver fibrosis in patients with hepatitis B. Results: Patients with stage S0-1, S2, S3, or S4 fibrosis did not differ significantly in terms of age or sex(P>0.05). ALT levels, AST levels, the PLT count, GGT levels, ALB levels, HBV-DNA levels, and the FIB-4 index and the APRI index differed significantly among the four groups of patients(P<0.05). The serum level of miR-223 was 1.37±0.15 in patients with stage S0-1 fibrosis, 2.05±0.21 in patients with stage S2, 2.84±0.36 in patients with stage S3, and 3.52±0.43 in patients with stage S4. The serum level of miR-223 was significantly higher than that in the control group(P<0.05). The serum level of miR-223 differed among patients with stage S0-1, S2, S3, or S4 fibrosis(P<0.05), and the higher the stage of liver fibrosis in patients, the higher the serum level of miR-223. Spearman correlation analysis indicated that serum miR-223 in patients with hepatitis B was positively correlated with the stage of liver fibrosis(r=0.564, P<0.01). Pearson correlation analysis indicated that serum miR-223 in patients with hepatitis B was positively correlated with APRI and Fib-4(r values: 0.525 and 0.621, P<0.01 for both). ROC curve analysis indicated that serum miR-223 had a certain diagnostic value at identifying different degrees of liver fibrosis, and especially for advanced fibrosis and liver cirrhosis. The area under the curve, sensitivity, and specificity were all higher than those for stage S0-2. Conclusion The serum level of miR-223 is elevated in patients with hepatitis B, and it is related to the degree of liver fibrosis. It can be used to assess the degree of fibrosis, and especially advanced fibrosis, in patients with hepatitis B.