| Objective: Hepatitis B virus associated Acute-on-chronic liver failure(ACLF)refers to a group of complex clinical syndromes with a critical condition and high mortality.The objective of this study was to investigate factors contributing to the clinical outcome and prediction of prognosis of patients with hepatitis B virus associated acute-on-chronic liver failure(HBV-ACLF),and to explore new predictive and/or prognostic biomarkers with high sensitivity and high specificity,and to establish the system for early forecasting the risk of ACLF,thus to provide new specific biomarkers and/or predict system for early identification of pre-ACLF,and provide theoretical foundation for clinical illumination of the early evolution course and early intervention of ACLF,so as to reduce the morbidity and mortality of ACLF and improve the outcomes accordingly.Methods: This study contains two parts,a retrospective study(Part 1),and a prospective cohort study(Part 2).In part 1,a retrospective study was conducted including a total of 138 patients with HBV-ACLF admitted to the Department of Infectious Diseases,Taihe Hospital,Hubei University of Medicine,from November 2013 to October 2016.The patients were divided into a poor prognosis group(74 patients)and a good prognosis group(64 patients)based on the disease outcomes.A comprehensive analysis was carried out in the context of parameters at the baseline status of all the patients,including the general information,such as gender,age,with/without(w/wo)liver cirrhosis,rebound after withdrawal of anti-viral drugs,complication with ascites at admission,and the acceptance and frequency of artificial liver support therapy,and the clinical indicators and the prognostic scores including CTP score,MELD score,MELD-Na score,iMELD score,and the ALBI score.The area under the receiver operating characteristic(ROC)curve was used to assess the predictive power of the five scoring systems for the prognosis of HBV-ACLF.The method of likelihood-ratio-forward-selection in non-conditional binary logistic regression analysis was used to obtain the independent risk factors and to establish a predictive model.In part 2,as a member of Chinese multicenter ACLF cohort study,the samples and clinical data of the patients enrolled in the ACLF multicenter prospective study cohort were shared.Patients with HBV-ACLF occurred liver failure within 28 days were screened and divided into survival group and death group according to the outcomes.Serum samples of the both groups were collected before and after the occurrence of ACLF.iTRAQ technology was used for screening the proteins expressed significant differences in plasma of the both two groups before and after the occurrence of ACLF.The difference larger than 1.5 times was considered as significant difference.Then potential biomarkers were screened from the differences protein as new predictors of pre-ACLF and/or ACLF.Results: The results of part 1 were shown as follows:1)Among the general information,the average age,the treatment with artificial liver support system and the number of such treatments were significantly different between the two groups of HBV-ACLF patients with distinct outcomes(P< 0.05);patients with good prognosis were much younger than those with poor prognosis,with average age of 43.16 ± 12.44 and 48.08 ± 9.08 years old,respectively.The number of patients who received artificial liver support therapy and the frequencies of artificial liver support therapy in the good prognosis group were significantly higher than those in the poor prognosis group(P < 0.01).There were no significant differences between the two groups with respect to sex,rebound after anti-viral drug withdrawal or the complications of cirrhosis and ascites(P > 0.05).2)There were no statistically significant differences between the two groups in terms of some certain clinical indicators,including LY,PLT,AST,Cr,PT,APTT and INR(P > 0.05).The levels of WBC,NE,NE/LY,ALT,GGT,TBil and Urea were significantly higher in the poor prognosis group(P< 0.05),while the Alb and Na levels in the good prognosis group were significantly higher than those in the poor prognosis group(P < 0.01).3)The CTP,MELD,MELD-Na,iMELD and ALBI scores of the patients with a good prognosis and the patients with a poor prognosis were 11.2 ± 1.68 vs.10.11 ± 1.78,21.58 ± 7.39 vs.18.08 ± 7.10,24.18 ± 10.11 vs.18.95 ± 7.7,40.75 ± 9.90 vs.33.79 ± 9.15,and-1.01 ± 0.54 vs.-1.34 ± 0.52,respectively.All of the five prognosis scores in the group of patients with a good prognosis were significantly higher than those in the patients with poor prognosis(P < 0.05).4)The ROC curves were used to investigate the value of the prognostic scores in the assessment of the short-term outcomes of HBV-ACLF,the areas under the ROC curves of the MELD,MELD-Na,CTP,ALBI,and iMELD prognostic systems were 0.639,0.656,0.672,0.682,and 0.699,respectively.5)NE/LY,GGT,Alb,Na,and artificial liver support therapy were the independent factors influencing the short-term outcomes of HBV-ACLF.A novel prediction model was established according to non-conditional binary logistic regression analysis: logit(p)= 3.068 + 1.003 × NE/LY-0.892 × GGT-1.138 × Alb-1.364 × Na + 1.651 × artificial liver support therapy.The information displayed in part 2 showed that:1)Compared with the survival group,24 kinds of proteins were increased and 6 kinds of proteins were reduced significantly in the plasma of patients with HBV-ACLF in the death group in the pre-ACLF phase;2.In the death group,4 kinds of proteins were increased and 34 kinds of proteins were significantly decreased in the ACLF phase,compared with that in the pre-ACLF phase in patients with HBV-ACLF.3.25 kinds of proteins/peptides were screened,and there predictive value in pre-ACLF and ACLF are under investigating.Conclusion: NE/LY ratio and serum levels of GGT,Alb,and Na were independent risk factors predicting short-term outcomes of HBV-ACLF,and multiple treatments with artificial liver support therapy in the early stage is conducive to improved short-term outcomes of HBV-ACLF.There are a variety of proteins changed in the occurrence and development of HBV-ACLF.It may provide a theoretical foundation for early clinical diagnosis and intervention of HBV-ACLF by exploring new protein markers in the early stage of the disease,and establishing of early predictive system for ACLF. |
