乙型肝炎肝硬化患者血清miR-122水平与肝纤维化程度的关系

The relationship between serum miR-122 levels and the degree of liver fibrosis in patients with hepatitis B-related cirrhosis

目的探讨乙型肝炎肝硬化患者血清miR-122水平与肝纤维化程度的关系。方法纳入2022年5月至2023年12月南京市高淳人民医院收治的乙型肝炎肝硬化患者98例,同时纳入健康者40名。检测所有研究对象血清中miR-122表达水平及肝脏生化指标。HBV-LC组中S0、S1、S2、S3、S4的患者分别为19、22、23、18、16例。比较不同分期患者的miR-122及肝脏生化指标水平差异,并比较血清miR-122水平与纤维化标志物间的相关性。logistic多元回归模型分析HBV-LC组患者肝纤维化的危险因素。结果HBV-LC组天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)、甲胎蛋白(AFP)、γ-谷氨酰转肽酶(GGT)水平及miR-122表达水平分别为(59.80±13.60)U/L、(67.89±14.94)U/L、(19.07±4.20)μmol/L、(13.06±3.88)ng/mL、(76.46±20.31)U/L、(4.03±1.38),均高于对照组的(23.23±5.17)U/L、(21.22±4.98)U/L、(11.33±3.05)μmol/L、(3.54±1.12)ng/mL、(29.81±7.28)U/L、(1.25±0.37),差异均有统计学意义(P<0.05)。随着肝纤维化分期的增加,HBV-LC组患者ALT、AST、TBil、AFP、GGT水平升高,miR-122表达水平降低(P<0.05)。HBV-LC组患者血清miR-122表达水平与AFP、AST、ALT、GGT、纤维化-4指数(FIB-4)、天冬氨酸氨基转移酶与血小板比值指数(APRI)、TBil和Forns指数均呈负相关(P<0.05)。logistic多元回归分析提示酗酒和血清miR-122表达水平较低是乙型肝炎肝硬化患者肝纤维化发生的危险因素(P<0.05)。miR-122表达水平诊断肝纤维化(S1~S4)的曲线下面积为0.939,灵敏度为94.7%,特异度为91.1%,显示出很高的诊断效能。结论乙型肝炎肝硬化患者血清miR-122水平随肝纤维化程度加重而降低,并与肝脏生化指标及纤维化标志物呈现出显著的相关性。酗酒以及低水平的血清miR-122表达是肝纤维化发展的危险因素。

Objective To investigate the association between serum miR-122 levels and the severity of liver fibrosis in hepatitis B-related cirrhotic(HBV-LC)patients.Methods A total of 98 blood samples were collected from HBV-LC patients from May 2022 to December 2023,forming the HBV-LC group.Meanwhile,blood samples from 40 healthy individuals were collected as the control group.Serum miR-122 expression levels and liver biochemical markers were tested in all participants.The HBV-LC group was divided into stage S0(19 cases),S1(22 cases),S2(23 cases),S3(18 cases),and S4(16 cases)based on the degree of liver fibrosis.The differences in miR-122 and liver biochemical markers across different stages were compared.The correlation between serum miR-122 levels and fibrosis markers were analyzed.A logistic regression model was used to analyze the risk factors for liver fibrosis in the HBV-LC group,and a ROC curve was constructed.Results In the HBV-LC group,the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT),total bilirubin(TBil),alpha-fetoprotein(AFP),gamma-glutamyltransferase(GGT),and the expression level of miR-122 were(59.80±13.60)U/L,(67.89±14.94)U/L,(19.07±4.20)μmol/L,(13.06±3.88)ng/mL,(76.46±20.31)U/L,and(4.03±1.38),respectively,which were significantly higher than those of(23.23±5.17)U/L,(21.22±4.98)U/L,(11.33±3.05)μmol/L,(3.54±1.12)ng/mL,(29.81±7.28)U/L,(1.25±0.37)in the control group(P<0.05).With the progression of liver fibrosis stages,the levels of ALT,AST,TBil,AFP,GGT increased,whereas the miR-122 expression decreased(P<0.05).Serum miR-122 expression levels in the HBV-LC group were negatively correlated with AFP,AST,ALT,GGT,Fibrosis-4 Index(FIB-4),AST to Platelet Ratio Index(APRI),TBIL,and Forns index(P<0.05).The result of Logistic regression analysis indicated that alcohol consumption and lower serum miR-122 expression levels are risk factors for liver fibrosis in HBV-LC patients(P<0.05).The ROC curve analysis demonstrated that miR-122 expression levels have a high diagnostic efficiency for liver fibrosis(S1~S4)with an area under the curve of 0.939,a sensitivity of 94.7%,and a specificity of 91.1%.Conclusion The study shows that serum miR-122 levels decrease as liver fibrosis worsen in patients with hepatitis B virus-related cirrhosis and are significantly correlated with liver biochemical markers and fibrosis markers.Alcohol consumption and low serum miR-122 expression are important risk factors for the progression of liver fibrosis.Therefore,serum miR-122 expression levels may serve as an effective biomarker for assessing the degree of liver fibrosis in patients with HBV-LC and predicting disease progression,thus offering significant clinical application value.