非酒精性脂肪性肝病患者血清miR-122、miR-140-5p和miR-34a水平变化及其临床意义探讨*

doi:10.3969/j.issn.1672-5069.2025.05.014

摘要/Abstract

摘要： 目的探讨非酒精性脂肪性肝病(NAFLD)患者血清微小RNA(miR)-122、miR-140-5p和miR-34a水平变化及其诊断非酒精性脂肪性肝炎(NASH)的效能。方法 2021年12月～2023年12月我院诊治的NAFLD患者104例和同期健康体检者60例,患者接受肝活检,采用实时荧光定量RT-PCR法检测血清miR-122、miR-140-5p和miR-34a水平,应用多因素Logistic回归分析NASH发生的危险因素,应用受试者工作特征曲线(ROC)并计算曲线下面积(AUC)评估血清miR水平诊断NASH的效能。结果在104例NAFLD患者中,经肝活检组织病理学检查诊断为NASH者43例,单纯性脂肪肝(SFL)61例;NASH患者血清miR-122和miR-34a水平分别为(8.1±1.3)和(1.8±0.4),显著高于SFL者【分别为(2.6±0.7)和(1.3±0.4),P＜0.05】或健康人【分别为(1.3±0.2)和(0.8±0.2),P＜0.05】,血清miR-140-5p为(24.1±5.1)×10^-4,显著低于SFL者【(71.2±11.3)×10^-4,P＜0.05】或健康人【(258.9±71.5)×10^-4,P＜0.05】;多因素Logistic回归分析显示,BMI(OR=1.793,95%CI:1.352～2.378)、ALT(OR=1.522,95%CI:1.127～2.055)、AST(OR=1.419,95%CI:1.205～1.671)、TG(OR=1.715,95%CI:1.194～2.463)、LDL-C(OR=1.537,95%CI:1.264～1.869)、HDL-C(OR=1.631,95%CI:1.207～2.204)、miR-122(OR=1.409,95%CI:1.228～1.617)、miR-140-5p(OR=0.639,95%CI:0.477～0.856)和miR-34a(OR=1.745,95%CI:1.162～2.621)均是影响NASH发生的独立危险因素(P＜0.05);经ROC分析,miR-122、miR-140-5p和miR-34a三项指标联合诊断NASH的AUC为0.954,其灵敏度为88.4%、特异度为90.2%、准确度为89.4%,显著优于各指标单独检测(P＜0.05)。结论应用血清miR-122、miR-34a和miR-140-5p水平可以诊断NASH患者,可帮助临床行初步筛查,值得进一步研究。

关键词: 非酒精性脂肪性肝病, 非酒精性脂肪性肝炎, 微小RNA-122, 微小RNA-140-5p, 微小RNA-34a, 诊断

Abstract: Objective This study was conducted to explore clinical implications of serum miR-122, miR-140-5p and miR-34alevels in patients with nonalcoholic fatty liver disease (NAFLD). Methods 104 patients with NAFLD and 60 healthy individuals for physical examination were encountered in our hospital between December 2021 and December 2023, and liver biopsies were performed in all patients with NAFLD. Serum miR-122, miR-140-5p and miR-34a levels were detected by real-time fluorescence quantitative RT-PCR. Risk factors of nonalcoholic steatohepatitis (NASH) were analyzed by multivariate Logistic regression. Receiver operating characteristic curve (ROC) and the area under the curve (AUC) were applied to evaluate diagnostic efficacy of serum miR-122, miR-140-5p, and miR-34a levels for NASH occurrence. Results Of 104 patients with NAFLD, NASH was found in 43 cases and simple fatty liver (SFL) was found in 61 cases based on NAFLD activity scores; serum miR-122 and miR-34a levels in NASH patients were (8.1±1.3) and (1.8±0.4), both significantly higher than [(2.6±0.7) and (1.3±0.4), respectively, P<0.05] in SFL patients or [(1.3±0.2) and (0.8±0.2), respectively, P<0.05] in healthy control, while serum miR-140-5p level in NASH patients was (24.1±5.1) ×10^-4, significantly lower than [(71.2±11.3) ×10^-4, P<0.05] in SFL patients or [(258.9±71.5) ×10^-4, P<0.05] in healthy persons; multivariate Logistic regression analysis showed that BMI (OR=1.793,95%CI: 1.352-2.378), ALT (OR=1.522,95%CI: 1.127-2.055), AST (OR=1.419,95%CI: 1.205-1.671), TG (OR=1.715,95%CI:1.194-2.463), LDL-C (OR=1.537,95%CI:1.264-1.869), HDL-C (OR=1.631,95%CI:1.207-2.204), miR-122 (OR=1.409,95%CI:1.228-1.617), miR-140-5 p (OR=0.639,95%CI:0.477-0.856) and miR-34a (OR=1.745,95%CI:1.162-2.621) were all the independent risk factors for NASH (P<0.05); ROC analysis showed that the AUC of combined serum miR-122, miR-140-5p and miR-34alevels for the diagnosis of NASH was 0.954, with the sensitivity of 88.4%, thespecificity of 90.2% and the accuracy of 89.4%, much superior to any one of the parameters alone (P<0.05). Conclusion Serum miR-122, miR-34aand miR-140-5p levels might help screening of patients with NASH in population of NAFLD, which needs further clinical investigation.

Key words: Nonalcoholic fatty liver disease, Nonalcoholic steatohepatitis, MicroRNA-122, MicroRNA-140-5p, MicroRNA-34a, Diagnosis

程中华, 唐楠, 谷硕, 李晨露. 非酒精性脂肪性肝病患者血清miR-122、miR-140-5p和miR-34a水平变化及其临床意义探讨^*[J]. 实用肝脏病杂志, 2025, 28(5): 695-698.

Cheng Zhonghua, Tang Nan, Gu Shuo, et al. Serum miR-122, miR-140-5p and miR-34a levels in patients with nonalcoholic fatty liver disease[J]. Journal of Practical Hepatology, 2025, 28(5): 695-698.

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非酒精性脂肪性肝病患者血清miR-122、miR-140-5p和miR-34a水平变化及其临床意义探讨^*

Serum miR-122, miR-140-5p and miR-34a levels in patients with nonalcoholic fatty liver disease

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