Serum Golgi Protein 73 Level In Chronic HBV Infection Associated Liver Disease And Its Clinical Significance

Objective: To investigate the serum GP73 level and its clinical significance in patients with chronic hepatitis,cirrhosis and liver cancer caused by chronic HBV infection.Methods: In this study,3604 patients with liver diseases related to chronic HBV infection were retrospectively collected.After screening by inclusion and exclusion criteria,1785 patients were finally included in this study,including 471 patients with chronic hepatitis B(CHB),907 patients with liver cirrhosis(LC)and 407 patients with hepatocellular carcinoma(HCC).At the same time,the preoperative information and postoperative survival data of 89 HCC patients undergoing hepatectomy were supplemented for postoperative survival analysis.According to the type of disease,the patients included in the study were divided into CHB group,LC group and HCC group,and the difference in the expression of serum GP73 level between groups was compared.Spearman correlation analysis was used to explore the correlation between serum GP73 and other serological indicators.Subgroup analysis was used to explore the effect of hepatitis B e antigen(HBe Ag)status and HBV DNA load on serum GP73 level and disease type.The principal component improved logistic regression was used to screen the significant factors affecting the degree of liver injury,and the diagnostic model of patients with moderate and severe liver injury was constructed and verified.The correlation between serum GP73 and Child-Pugh score of liver function was analyzed,and the serum levels in patients with compensated cirrhosis and decompensated cirrhosis were compared to illustrate the clinical significance of serum GP73 in patients with LC.The effect of liver cirrhosis background on serum GP73 level in HCC patients was investigated by 1 : 1 matching and its effect on postoperative survival of HCC patients was analyzed.Based on Cox proportional hazard regression,a plot model was constructed to predict the postoperative survival of HCC patients.Calibration correction curve and consistency index(C-index)were used to evaluate the predictive efficiency of the model.Results: 1.In this study,the serum GP73 median level of CHB patients was significantly lower than that of LC(54.1 vs.102.2 ng/m L,P < 0.001)and HCC patients(54.1 vs.95.8 ng/m L,P < 0.001),while the serum GP73 median level of LC patients were not significantly different from that of HCC patients(102.2 vs.95.8 ng/m L,P = 0.124).2.In CHB patients,serum GP73 was significantly positively correlated with AFP,ALT,AST and GGT(r = 0.585,P < 0.001,r = 0.557,P < 0.001;r = 0.610,P < 0.001;r = 0.568,P < 0.001),negatively correlated with PAB(r =-0.547,P < 0.001).The serum GP73 level in LC patients was significantly positively correlated with AFP,PT,INR,AST,TBil,TBA and other indicators(r = 0.537,P < 0.001,r = 0.627,P < 0.001;r = 0.638,P < 0.001;r = 0.632,P < 0.001;r = 0.506,P < 0.001;r = 0.630,P < 0.001),which was significantly negatively correlated with PAB,ALB and CHE(r =-0.702,P < 0.001;r =-0.641,P < 0.001;r =-0.674,P < 0.001).For patients with HCC,only PAB and ALB had obvious negative correlation with serum GP73(r =-0.567,P < 0.001;r =-0.475,P < 0.001),with weak or no significant correlation with other indicators.3.Regardless of the HBe Ag status of patients,the median serum GP73 level of CHB patients was significantly lower than that of LC patients(Positive: 68.3 vs.120.7 ng/m L,P < 0.001;Negative: 43.5 vs.94.2 ng/m L,P < 0.001)and HCC patients(Positive: 68.3 vs.112.6 ng/m L,P < 0.001;Negative: 43.5 vs.79.1 ng/m L,P < 0.001).There was no significant difference in the median serum GP73 level between LC and HCC patients(Positive: 120.7 vs.112.6 ng/m L,P = 0.102;Negative: 94.2 vs.81.2 ng/m L,P = 0.074).In the same disease state,the median level of serum GP73 in HBe Ag-positive patients was significantly higher than that in HBe Ag-negative patients(69.4 vs.43.5 ng/m L,P < 0.001;120.7 vs.94.2 ng/m L,P < 0.001;112.9 vs.79.1 ng/m L,P < 0.001).4.In the low HBV DNA loading group,there was no significant difference in the median level of serum GP73 between LC and HCC patients(83.1 vs.79.4 ng/m L,P > 0.999).The median level of serum GP73 in LC patients was significantly higher than that in HCC patients(150.0 vs.92.5 ng/m L,P < 0.001).In the high load group,the median serum GP73 level of LC patients still were significantly higher than that of HCC patients,but there was no significant difference in the median serum GP73 level between HCC patients and CHB patients(99.4 vs.83.6 ng/m L,P > 0.999).Under the same disease type,the serum GP73 levels of patients with different viral load groups showed an upward trend with the increase of HBV DNA load,but the increase rates were different.Patients with LC showed the largest increase,followed by patients with CHB,and patients with HCC showed the smallest increase.5.In CHB patients without cirrhosis,the serum GP73 level increased significantly with the increase of inflammatory activity and fibrosis degree.ROC curve showed that the diagnostic efficacy of serum GP73 in patients with moderate to severe liver injury was AUC = 0.719(95%CI: 0.650-0.781,P = 0.042),and there was no significant difference compared with ALT(0.719 vs.0.633,P = 0.101).Establishment of a diagnostic model for moderate to severe liver injury based on principal component improved Logistic regression,namely Logit(P)=(0.510 × GP73 + 13.107 × PT-0.817 × PLT + 0.345 × ALT + 0.413 × AST-0.719 × PAB-3.876 × ALB + 1.353 × GGT-28.547)/ 100.After verification,the diagnostic efficacy of this model for patients with moderate to severe liver injury was AUC = 0.833(95%CI: 0.724-0.943,P < 0.001).With the optimal cut-off value as the boundary,the sensitivity and specificity were 72.37 % and 92.31 %,respectively.6.For patients with LC,the serum GP73 level in patients with compensated stage was significantly lower than that in patients with decompensated stage(71.0 vs.137.7 ng/m L,P < 0.001),and the diagnostic efficacy AUC of serum GP73 for patients with decompensated cirrhosis was 0.734(95 %CI: 0.704-0.762),which was between FIB-4 index(0.763 vs.0.734,P > 0.005)and APRI score(0.709 vs.0.734,P > 0.005).In addition,the serum GP73 level of LC patients were also significantly increased with the Child-Pugh classification of liver function(77.5 vs.175.6 vs.253.5,ng/m L,P < 0.01).The scatter plot showed that the serum GP73 level of LC patients was positively correlated with the Child-Pugh score(r = 0.679,P < 0.001).7.With HCC patients with non-LC background as the control group,1:1 matching was performed on CHB patients,LC patients and HCC patients with LC background, respectively.The comparison showed that the serum GP73 levels of HCC patients with LC and LC backgrounds were significantly higher than those of HCC patients with CHB and non-LC backgrounds(P < 0.01).There was no significant difference in serum GP73 level between LC and LC background HCC patients and between CHB and non-LC background HCC patients(168.5 vs.159.4,P=0.801;86.2 vs.89.6,P=0.999).Prognostic survival analysis of 89 HCC patients undergoing hepatectomy showed that the median postoperative survival time of patients with low serum GP73 was significantly higher than that of patients with high serum GP73(40.5 vs.20.3 months,P = 0.017).After univariate and Cox multivariate regression analysis,PT > 13.5 s,AFP > 200 ng/ml,GP73 > 70 ng/ml and GGT > 70 U/L were independent risk factors affecting the survival of HCC patients after resection.With these four risk factors as independent variables,the survival prediction model of HCC patients was constructed,and the correction curve was drawn after internal verification.The Cindex was calculated to be 0.667(P = 0.035).Conclusion: 1.The serum GP73 level in patients with chronic HBV infection-related liver diseases is mainly related to disease progression,liver injury and liver metabolic function.And serum GP73 levels showed different upward trends with the increase of HBV DNA load.2.In terms of single index,compared with ALT,serum GP73 has higher diagnostic value for moderate and severe liver injury.The diagnostic model of moderate and severe liver injury constructed in this study significantly improves the diagnostic efficiency of serum GP73,and provides reference for its practical clinical application.3.For patients with liver cirrhosis,the serum GP73 level in decompensated patients was significantly higher than that in compensated patients,and the serum GP73 level was positively correlated with the Child-Pugh score of liver function,which can reflect the liver function status of patients with liver cirrhosis in real time,and can be used as a clinical liver function monitoring index for patients with liver disease.4.Liver cirrhosis background is a mixed factor affecting the diagnosis of HCC patients with elevated serum GP73 level.However,the high level of serum GP73 has a significant predictive effect on the short postoperative survival of HCC patients.The survival prediction model of HCC patients constructed with serum GP73 can better predict the postoperative survival rate of patients.