Application Value Of Circulating Ribonucleotide Reductase In The Diagnosis And Evaluation Of Liver Cirrhosis

Backgrounds Ribonucleotide reductase(RR)is the basic material for DNA synthesis in all organisms.It catalyzes the synthesis of deoxyribonucleotide diphosphates(d NDPs)and provides d NTPs for DNA synthesis.It is not only the unique enzyme in the process of converting ribonucleotides into deoxyribonucleotides,but also a key enzyme in DNA synthesis and repair.It has been confirmed that RR in the human body is mainly composed of three subunits: RRM1,RRM2 and p53 R,p53R is a newly discovered subunit which is also called RRM2 B.Studies have shown that RR is closely related to hepatocyte self-repair,hepatoma expansion and hepatophilic virus replication.However,there are still few studies on clinical research on RR enzyme,especially in chronic liver disease.In order to study the clinical value of ribonucleotide reductase in the diagnosis and evaluation of chronic liver disease,we analyzed the circulating RRM2 in patients with chronic liver disease(Hepatitis B cirrhosis,alcoholic cirrhosis and autoimmune cirrhosis)in the connection with common clinical assay indicators and draw the ROC(Receiver operating characteristic)curve to predict the diagnostic efficiency of RRM2 in HBV-related cirrhosis and the evaluation of cirrhosis stage.Methods: we collected 187 cirrhosis patients,33 patients with chronic hepatitis B virus and 30 healthy controls in the outpatient and inpatient wards of the First Affiliated Hospital of Zhejiang University from August,2019 to Feburary,2020.According to the clinical diagnosis of patients,the liver cirrhosis group was divided into two subgroups-84 cases of compensatory liver cirrhosis(40 cases of hepatitis B cirrhosis,23 cases of alcoholic cirrhosis,21 cases of autoimmune cirrhosis),103 cases of decompensated cirrhosis cases(50 cases of HBV cirrhosis,30 cases of alcoholic cirrhosis,23 cases of autoimmune cirrhosis).Enzyme-1inked Immunosorbent assay(ELISA)was used to detect RRM2 in the blood expression level,the difference between RR enzyme subunits was compared between groups by t-test and analysis of variance.The ROC curve and area under curve(AUC)were used to compare the diagnostic efficiency and the role of evaluation in staging of liver cirrhosis.The AUC under different curves was compared using the z-test.At the same time,multiple regression analysis was used to screen out clinical test indicators that related to RRM2,and further draw the relevant curves.Results:(1)Circulating RRM2 levels in patients with alcoholic cirrhosis and autoimmune cirrhosis were significantly lower than those in patients with hepatitis B cirrhosis and chronic hepatitis B,and there was either no statistically significant difference with healthy controls.At the same time,the circulating RRM2 level of patients with HBV-related cirrhosis was significantly higher than that of patients with chronic hepatitis B(3790U / L vs.1804 U / L,P <0.01),and the patients with different stage had significant differences(hepatitis B compensation phase vs.hepatitis B decompensation 2909 vs.4525 U / L,P = 0.017).(2)The evaluation efficiency of RRM2 in the decompensation period of patients with hepatitis B cirrhosis was better than LN and HA,and there was no significant differences compared with PIIINP,CIV,and MELD scores(RRM2: AUC = 0.72,95% CI: 0.61-0.83).In contrast,RRM2 had a similar diagnosis efficiency with FIB-4 of HBV cirrhosis(AUC 0.68 vs.0.73,P = 0.45),and was better than APRI(AUC 0.73 vs.0.53,P <0.01).In terms of diagnostic sensitivity and specificity,RRM2 is better than APRI and FIB-4.(3)we analysed the variables that affected serum RRM2 concentration in patients with chronic hepatitis B and hepatitis B cirrhosis by multiple regression analysis,and suggested that HBs Ag(hepatitis B surface antigen)and HBe Ag were significantly correlated with RRM2 concentration in patients with hepatitis B.The correlation was further confirmed and the prediction equation was calculated,while patients with chronic hepatitis B did not get significant correlation results.There was no significant relation between circulating RRM2 and HBV-DNA in chronic hepatitis B or HBV-related cirrhosis patients.(4)In the high ALT and AST groups,the correlations between RRM2 and HBs Ag,HBe Ag,and HBV-DNA in patients with hepatitis B were improved compared with the normal level group.Conclutions: Circulating RRM2 has a certain clinical utility in the diagnosis and staging evaluation of HBV-related cirrhosis,but it has no significant effect on patients with alcoholic cirrhosis and autoimmune cirrhosis.There is a certain correlation between the concentration of hepatitis B surface antigen and hepatitis B e antigen with the concentration of RRM2.RRM2 can reflect the destruction of liver cells and the degree of replication activity of hepatitis B virus to a certain extent.