An Optimal Predictive Model To Assess The Poor Prognosis Of Hepatitis B-related Acute-on-chronic Liver Failure Patients Based On Red Blood Cell Distribution Width

Objective: Acute-on-chronic liver failure(ACLF)is a serious clinical syndrome that results from culmination of chronic liver disease and leads to one or more organ failures,which has been shown to carry poor prognosis with a short-term mortality rate of > 50%.So,a role for early assessment of the risk of death in patients with ACLF and select appropriate treatment is being increasingly recognized.However,there are some inherent limitations of the prognostic model which was widely used now in clinic because of inconsistent diagnostic criteria and factors of basic diseases.Otherwise,the factors about basic diseases of chronic liver disease in China are mostly caused by hepatitis B virus(HBV).Since these predictive scoring models are not suitable for the mortality of Hepatitis B-related acute-on-chronic liver failure(HBV-ACLF)patients,it is necessary to establish an efficient prognostic model for the disease using the more stable and more independent parameters.Red blood cell distribution width(RDW)reflects heterogeneity of red blood cells(RBC)and is a routine parameter of the complete blood count.RDW is now believed to be a useful parameter for either the diagnostic or prognostic evaluation of cardiovascular diseases,kidney disease,sepsis.Recently,emerging evidence suggests that increased RDW was associated with outcome in patients with chronic liver disease and severity of liver disease.Thepresent study was designed to investigate the association between RDW values and different disease states in HBV-infected patients and the application value of RDW in predicting short-term prognosis in patients with HBV-ACLF.Accurately predicting the prognosis of individual patient is crucial in the management of ACLF.We aimed to establish RDW-MELD prognostic model for HBV-ACLF patients.we focused on improve the evaluation value of short-term death in patients with HBV-ACLF,guide better clinical treatment,determine the risk of early death in patients,provide more suitable treatment choice.Methods: 200 cases of Adult HBV-infected patients admitted to the Affiliated Hospital of Southwest Medical University and diagnosed with CHB or HBV-ACLF were consecutively recruited between January 2018 and December2018.We retrospectively collected their clinical information and routine hematological testing,liver function,renal function.During the same time period,age-and sex-matched healthy individuals were recruited as controls at a patient/control ratio of 1:1.In the present study,the differences in RDW in the three groups were analyzed to verify whether RDW could reflect the severity of the liver.We enrolled 245 patients with HBV-ACLF admitted to the Affiliated Hospital of Southwest Medical University from January,2014 to December,2017 as derivation cohort,retrospectively collecting their clinical data and routine hematological testing,liver function,renal function,coagulation test,HBV-DNA,and other indicators from patients at admission.Correlationanalysis between RDW and laboratory parameters and MELD scores using Spearman's correlation analysis.Univariate analysis,binary logistic regression analysis and other methods were used to test the risk factors of HBV-ACLF patients,and the RDW-MELD model was established by Cox's proportional hazards regression model.The accuracy of each index and the established model was verified by receiver operating characteristic curve(ROC).A total of84 patient hospital as HBV-ACLF from January 2018 to September 2018 in the Affiliated Hospital of Southwest Medical University were used as a validation group,retrospectively collecting their clinical data and routine laboratory test indicators.Match clinical data and laboratory test indicators to the model group.The clinical value of the prognostic model was evaluated through ROC analysis.Results: Compared with RDW(12.68�0.61%)in healthy individuals,the RDW in were significantly increased in the patients with CHB(14.50�1.14%)and HBV-ACLF(16.49�3.07%),and HBV-ACLF group was higher than CHB group.RDW(14.97�1.38%)and MELD score(23.54�4.35)in the survival group patients with HBV-ACLF was significantly decreased compared to those in the death group(17.05�2.92%)and(28.95�5.99).Furthermore,Spearman's correlative analysis indicated slightly positive correlation of RDW with MELD score(r=0.256,P=0.001)and NEU-R(r=0.135,P=0.034),Grea(r=0.169,P=0.008),TBIL(r=0.273,P=0.001).In addition,the RDW values were negative correlated with RBC(r=-0.273,P=0.001)and HGB(r=-0.349,P=0.001),ALB(r=-0.179,P=0.005).The RDW(OR=1.840,95%CI:1.479~2.289)and MELD score(OR=1.154,95%CI:1.030~1.293),Hepatic encephalopathy(OR=1.154,95%CI : 1.030~1.293)were an significant independent prognostic index for mortality in patients with HBV-ACLF on multivariate analysis.However,ALB(OR=0.921,95%CI:0.853~0.994)and PTA(OR=0.943,95%CI:0.894~0.994)is a protective factor for short-term mortality in patients with HBV-ACLF.In this study,the short-term mortality rate of HBV-ACLF patients was 50.6%.The short-term mortality rate was significantly higher in the patients who had RDW > 16.6% compared with those who had RDW? 16.6%.In order to improve the prediction performance,the model is built to include objective indicators.So,the risk assessment model was Cox RDW-MELD=1.341� RDW-0.043� ALB-0.043� PTA+ 0.894� MELD,the model has a cutoff value of 42.605,a sensitivity of 0.718,and a specificity of 0.860.The area under the ROC curve of MELD score combined with RDW was 0.861,which was higher than RDW(0.724)and MELD score(0.780).In the verification queue,the value of RDW-MELD model was 0.811,which was also higher than RDW(0.722)and MELD score(0.765).Conclusions:(1)Compared with healthy individuals,the level of RDW in patients with CHB and HBV-ACLF were significantly increased.In addition,compared with survivor group,the value of RDW of the non-survivor group were significantly increased in patients with HBV-ACLF.Indicates that RDW is associated with the severity of hepatitis B virus-associated liver disease.(2)Thelevel of RDW were positively correlated with MELD scores and NEU-R,Grea,TBIL in patients with HBV-ACLF,the RDW values were negative correlated with RBC and HGB,ALB.Furthermore,RDW was a significant independent prognostic index for short-term mortality in patients with HBV-ACLF on multivariate analysis.Indicating that RDW indicators may be related to the prognosis of disease.(3)In the study of short-term prognosis of HBV-ACLF,the value of RDW and MELD score,hepatic encephalopathy was a significant independent prognostic indicator for the mortality rate in patients with HBV-ACLF on multivariate analysis.The value of ALB and PTA were a protective factor for short-term mortality in patients with HBV-ACLF.(4)A new Cox's proportional hazards regression model named RDW-MELD was based on RDW.The model was proved to have excellent predictive performance by verifying the validation group.It can be used to judge prognosis and assess the survival rate of early stage in patients with HBV-ACLF.