血清miR-203和壳多糖酶3样蛋白1联合检测对肝显著纤维化/肝硬化的诊断价值

The diagnostic value of combined detection of serum miR-203 and chitinase 3-like protien 1 for liver significant fibrosis/cirrhosis

目的探讨微小RNA(miR)-203和血清壳多糖酶3样蛋白1(CHI3L1)单独及联合诊断肝显著纤维化/肝硬化的价值。方法将该院2022年1月至2022年12月住院的慢性乙型肝炎(CHB)患者80例纳入研究,同时选取体检健康者40例作为健康对照组。根据组织检查结果将纳入研究的CHB患者分为无/轻度纤维化组(50例)和肝显著纤维化/肝硬化组(30例)。检测各组血清miR-203和CHI3L1水平,肝纤维化4项[Ⅲ型前胶原(P-Ⅲ)、Ⅳ型胶原(C-Ⅳ)、层粘连蛋白(LN),透明质酸酶(HA)]和生化指标[丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)],计算天门冬氨酸氨基转移酶-血小板比值指数(APRI)、肝纤维化指数(FIB-4)。用非参数秩和检验进行组间各项指标的比较。用Spearman相关进行miR-203和CHI3L1与肝纤维化指标的相关性分析。采用受试者工作特征(ROC)曲线评估miR-203和CHI3L1单独和联合对肝显著纤维化/肝硬化的诊断效能。结果miR-203与C-Ⅳ、HA、FIB-4、ALT呈负相关(r=-0.282、-0.318、-0.238、-0.224,P<0.05),与血小板计数(PLT)呈正相关(r=0.298,P<0.05)。CHI3L1与C-Ⅳ、HA、LN、FIB-4、APRI、ALT呈正相关(r=0.296、0.467、0.254、0.284、0.300、0.316,P<0.05),与PLT呈负相关(r=-0.506,P<0.05)。ROC曲线显示miR-203预测肝显著纤维化/肝硬化发生的曲线下面积(AUC)为0.820,CHI3L1预测疾病的AUC为0.873,均优于APRI和FIB-4(P<0.05),两者联合诊断的AUC为0.895;抗病毒治疗后miR-203和CHI3L1水平与治疗前比较,差异有统计学意义(P<0.05)。结论血清miR-203和CHI3LI的检测可用于肝显著纤维化/肝硬化诊断和抗病毒疗效的评价,两者联合应用可提高诊断效能。

Objective To investigate the value of miR-203 and serum chitosanase 3-like protein 1(CHI3L1)alone and in combination for the diagnosis of significant liver fibrosis/cirrhosis.Methods Eighty patients with chronic hepatitis B(CHB)who were hospitalized in the hospital from January 2022 to December 2022 were enrolled in the study,while 40 cases of healthy medical examiners were enrolled as the healthy control group.The CHB patients enrolled in the study were divided into the group with no/mild fibrosis(50 cases)and the group with significant fibrosis/cirrhosis(30 cases)based on the results of tissue examination.Serum miR-203 and CHI3L1 levels,four items of hepatic fibrosis[pre-collagen typeⅢ(P-Ⅲ),collagen typeⅣ(C-Ⅳ),laminin(LN),and hyaluronidase(HA)]and biochemical indexes[alanine aminotransferase(ALT)and aspartate aminotransferase(AST)]were detected in each group,and the aspartate aminotransferase-platelet ratio index(APRI),and liver fibrosis index(FIB-4)were calculated.Comparison of the indices among groups was performed using the nonparametric rank sum test.Correlation analysis of miR-203 and CHI3L1 with liver fibrosis indices was performed using Spearman correlation.The diagnostic efficacy of miR-203 and CHI3L1 alone and in combination for significant hepatic fibrosis/cirrhosis was assessed using the receiver operating characteristic curve(ROC).Results The level of serum CHI3L1 was positively correlated with C-Ⅳ,HA,LN,FIB-4,APRI,ALT(r=0.296,0.467,0.254,0.284,0.300,0.316,P<0.05)and negatively correlated with PLT(r=-0.506,P<0.05).The level of serum miR-203 was negatively correlated with(C-Ⅳ,HA,FIB-4,ALT)(r=-0.282,-0.318,-0.238,-0.224,P<0.05)and positively correlated with PLT(r=0.298,P<0.05).The ROC curves showed that the area under the curve of miR-203 for predicting the development of significant hepatic fibrosis/cirrhosis was 0.820,and the AUC of CHI3L1 for predicting the disease was 0.873,which were better than those of APRI and FIB-4(P<0.05),and the AUC for the combined diagnosis was 0.895;after antiviral treatment,the levels of miR-203 and CHI3L1 were compared with those of pre-treatment,the difference was statistically significant(P<0.05).Conclusion Serum miR-203 and CHI3LI assays can be used for the diagnosis of significant liver fibrosis/cirrhosis and the evaluation of antiviral efficacy,and the combination of the two can improve the diagnostic efficacy.