Clinical value of dynamic monitoring of blood GP73 and autophagy-related proteins on short-term prognosis of HBV-related ACLF
Objective To dynamically monitor Golgi protein 73(GP73),p62,autophagy-related proteins(Beclin1),microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)in patients with hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF),and explore its short-term prognostic value.Methods A total of 120 HBV-ACLF patients(study group)and 50 healthy subjects(control group)during the same period were selected From January 2016 to December 2019 in No.910 Hospital,Joint Logistics Support Force of the Chinese People's Liberation Army as the research subjects,and the differences in blood GP73,p62,Beclin1 and LC3-Ⅱ between the two groups of patients were compared.Real-time monitoring of blood GP73,p62,Beclin1 and LC3-Ⅱ changes in the study group at different time periods since admission(on 0,1 and 2 months of admission),and analyzing their correlation with HBV-DNA viral load and model for end-stage liver disease(MELD)score.The study group was divided into survival group(n=71)and death group(n=49)based on the short-term prognosis(clinical outcome)3 months after admission.Compare the differences in blood GP73,p62,Beclin1 and LC3-Ⅱ in different time periods between the survival group and the death group.The Cox regression model was used to analyze its impact on the clinical outcomes of HBV-ACLF,and a receiver operating characteristic(ROC)curve was drawn to analyze its predictive value for clinical outcomes.Results Compared with the control group,peripheral blood GP73,Beclin1 and LC3-Ⅱ were all increased and p62 was decreased in the study group at different time periods(on 0,1 and 2 months of admission),and the differences were statistically significant(F=29.485,12.485,21.371,10.873;all P<0.05).Comparing the peripheral blood GP73,p62,Beclin1,LC3-Ⅱ,HBV-DNA load and MELD score at different time periods between the survival group and the death group,the differences were statistically significant(F=37.982,13.256,18.373,30.275,12.784,20.381,all P<0.05).Pearson correlation analysis showed that at different time periods(on 0,1 and 2 months of admission),the HBV-DNA load of HBV-ACLF patients were positively correlated with GP73(r=0.721,0.734,0.715),Beclin1(r=0.683,0.726,0.717)and LC3-Ⅱ(r=0.634,0.672,0.659),and negatively correlated with p62(r=-0.694,-0.703,-0.711).The MELD score of HBV-ACLF patients was positively correlated with GP73(r=0.784,0.752,0.769),Beclin1(r=0.815,0.794,0.836)and LC3-Ⅱ(r=0.859,0.873,0.848),and negatively correlated with p62(r=-0.749,-0.802,-0.786);the above differences were all statistically significant(all P<0.05).Cox regression analysis revealed that GP73,p62,Beclin1 and LC3-Ⅱ could affect the clinical outcome of HBV-ACLF at different time periods(on 0,1 and 2 months of admission)(all P<0.05).Among them,GP73,p62,Beclin1 and LC3-Ⅱ had the greatest impact on the clinical outcome of HBV-ACLF in the 0th month of admission,with absolute HR values of 2.673,2.132,2.498 and 2.995,respectively.The results of GP73,p62,Beclin1 and LC3-Ⅱ in the 0th month of admission were selected for analysis,and the ROC curve was drawn to show that the areas under the curve(AUC)of GP73,p62,Beclin1 and LC3-Ⅱ in predicting the clinical outcome of HBV-ACLF were 0.588,0.531,0.582 and 0.549,respectively;the combination of the four had the best predicting value(AUC=0.871)(P<0.05).Conclusions GP73,p62,Beclin1 and LC3-Ⅱ were all abnormally expressed in HBV-ACLF at different time points,which were related to HBV-DNA load and MELD score,and could affect the clinical outcome of HBV-ACLF,among which the greatest impact was on initial admission.GP73,p62,Beclin1 and LC3-Ⅱ could be used to predict the clinical outcome of HBV-ACLF,and the combination of the four had the best effect.
Hepatitis B virusAcute-on-chronic liver failureGolgi protein 73Autophagy-related proteinsShort-term prognosis