| Objective: To analyze the levels of serum soluble urokinase plasminogen activator receptor(su PAR)for the patients with hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)and its association with prognosis.Methods: This study describes the su PAR changes of clinical features in patients with HBV-ACLF; Explore the relationship between serum su PAR levels and short-term prognosis of patients with HBV-ACLF, and the relationship with the traditional inflammatory markers such as CRP, PCT. Analysis of Cox multiple factors affecting the risk factors prognosis of patients with HBV-ACLF, assessment HBV-ACLF the short-term prognosis prediction model has been constructed and verified the predictive value of the model. The research carried out from the following three aspects:First, the cross-sectional study: selected 60 case patients who were occurred in our hospital and diagnosed of HBV-ACLF were enrolled from December 2012 to September 2014, 33 cases chronic HBV carriers who outpatient during same period in our hospital and 33 healthy controls from Medical University of Fujian First Affiliated Hospital Health Examination Center. Enrolled HBV-ACLF patients in line with the Guideline for diagnosis and treatment of liver failure(2012 version), Chronic HBV carriers in conformity with the guideline of prevention and treatment for chronic hepatitis B(2010 version).Collect serum of 60 cases HBV-ACLF?33 cases chronic HBV carriers and 33 cases health control. Detection of serum su PAR content with the method of enzyme-linked immunosorbent assay(ELISA).analyzed these difference in the different groups; Dividing all the HBV-ACLF patients into survivors and nonsurvivors group, observed all patients with baseline su PAR level differences.To investigate the predictive value of su PAR levels and the prognosis of patients withHBV-ACLF; And explore the relationship between the level of su PAR and CRP, PCT,MELD score, HBV DNA load, liver function and blood coagulation function;Second, the longitudinal study: selected 50 cases with HBV-ACLF whose case information were full range in the 60 HBV-ACLF patients. Dynamic monitoring of 50 cases HBV-ACLF patients with su PAR?CRP and PCT at baseline, 2 week and 4 week point. According to 12 week of follow-up ending will HBV-ACLF patients is divided into survived group and death group, analysis serum su PAR, and CRP, and PCT level changes trend of both group. Analysis of correlation between su PAR and CRP, PCT by Pearson correlation. ROC curve analysis and comparison of dynamic su PAR and CRP,PCT change, MELD score in the prognosis of patients with HBV-ACLF diagnosis.Third, Modeling and Validation Study: Analyses the 60 cases HBV-ACLF patients in Kaplan-Meier Survival Analysis in 12 weeks, using Cox regression models to explore the risk factors influencing the prognosis of patients with HBV-ACLF; and build a HBV-ACLF short-term prognosis of forecast model; Analysis the model of forecast index(PI) and MELD score and the Ln(su PAR) wirh ROC curve, evaluation the model on HBV-ACLF patients prognosis assessment of capacity;According to the best critical value of PI, put the 60 cases HBV-ACLF patients of PI value for II classification divided, the positive is greater than best critical value,otherwise negative. Analyzing the impact of PI on survival of patients with HBV-ACLF with Cox return survival function figure.And enrolled 50 cases HBV-ACLF patients in line with the Guideline for diagnosis and treatment of liver failure(2012 version),determination the su PAR, and collection related clinical information, calculation Cox value, validation Cox model diagnosis value for prognostic evaluation of patients with HBV-ACLF.Result: First, the cross-sectional study: The su PAR levels of HBV-ACLF patients group ? Chronic HBV carriers group and healthy control group have significant difference(P<0.001);Lg(HBVDNA)and HBe Ag had no significant difference between HBV-ACLF and chronic HBV carriers group. And age, sex were no significant difference in the three groups people.Follow up all the liver failure patients for 3 months,we discoveried there were 15 cases were death, and the mortality was 25%; besides, theserum su PAR levels had significant difference(P < 0.001) between the survival group and nonsurviva group. There was a certain relationship between su PAR level in serum and The prognosis of patients with HBV-ACLF. In the follow-up of 3 months, there were 45 cases got infection, the infection rate was 75%, the serum su PAR level had significant difference(P < 0.001) between infection group and non infection group.The CRP,PCT, WBC, N%, INR, MELD score levels were positive correlated with su PAR level,while the PTA level was negatively related to the su PAR level.Second, longitudinal studies: dynamic analysis of 50 patients with HBV-ACLF three levels of serum su PAR, CRP, PCT at 0 weeks, 2 weeks and 4 weeks, CRP, PCT levels and the relative, dynamic follow-up showed three, su PAR, CRP, PCT in HBV-ACLF death group upward trend and a downward trend in the survival of the group and the survival group of su PAR, CRP, PCT levels were significantly higher than the survival of each group level; three dynamic follow-up, su PAR and CRP, su PAR and PCT are significantly strong positive correlation(P <0.05), can be considered su PAR and CRP, PCT, was a good indicator of inflammation; HBV-ACLF patients 0 weeks,two weeks, four weeks serum su PAR levels and three periods death HBV-ACLF patients are positively correlated, the P-value less than 0.05, with statistical significance.Third, Modeling and Validation Study: Kaplan-Meier survival analysis showed that 60 cases of HBV-ACLF median survival time was 78.183 days(95% CI71.848-84.519 days), a sharp decline curve in 58 days, during which time within a proactive and effective treatment has a great influence on the prognosis; Cox regression analysis showed that patients with HBV-ACLF risk factors are: age,liver failure staging,merged infection, hepatic encephalopathy, Hemorrhage of upper digestive tract,Ln(su PAR), N%, CRP, PCT, TBIL, BUN, INR, and MELD; According to on HBV-ACLF patients survival time has effect of dangerous factors and return coefficient, can obtained Cox return model of forecast index(PI): PI=0.247* age(age) +0.091 liver failure staging(early for 1, and medium-term for 2, and late for 3) +5.312 whether merged infection(has for 1, and inaction 0) +0.494* hepatic encephalopathy(inaction stage 0, stage I is 1 and II 2, stage 3, stage 4) +4.789* of upper digestive tract hemorrhage(1, 0 of doing nothing) +1.136*Ln(su PAR)(pg/m L) +0.39* CRP(mg/l)+0.338*PCT(ng/L) +0.011*TBIL(?-mol/L) +0.709*BUN(mmol/L)+1.180*INR+0.128* MELD. Calculated PI value of the 60 patients with liver failure,also with the MELD score and Ln(su PAR) ROC curve analysis, PI(AUC0.873;P<0.001), MELD score(AUC 0.682;P=0.036), Ln(su PAR)(AUC0.816;P<0.001), PI of the AUC is one of the largest, sensitivity is 0.867, Specificity is0.822, its prognostic value in patients with HBV-ACLF; HBV-ACLF of PI-negative survival time significantly longer than the survival time of patients with PI-positive HBV-ACLF. 50 patients with HBV-ACLF of late into calculating PI values, also with the MELD score and Ln(su PAR) ROC curve analysis, PI(AUC 0.936;P<0.001),MELD score(AUC 0.659;P=0.045), Ln(su PAR)(AUC 0.753;P=0.002), the AUC of PI is the largest, the diagnostic value of PI is superior to the MELD score and Ln(su PAR);In that 50 cases of HBV-ACLF in patients with HBV-ACLF of PI-negative survival time significantly longer than the survival time of patients with PI-positive HBV-ACLF.Conclusion:(1) The serum su PAR levels in patients with HBV-ACLF was higher than that of chronic HBV carriers and higher than that in healthy people;(2) su PAR and CRP, PCT in liver failure process showed significant positive correlation;(3)su PAR is an important evaluation index of degree of inflammation in HBV-ACLF, su PAR is higher, the more severe the degree of inflammation, the illness is more serious;(4) The construction of the Cox model which contains su PAR has a high predictive value for the short-term prognosis of HBV-ACLF patients;... |
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