Clinical Efficacy And Prognosis Of Non-bioartificial Liver Support System Combined With Liver Transplantation In Patients With HBV-related Acute-on-chronic Liver Failure

Backgrounds and Objectives Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)is a serious stage of the development of Hepatitis B.It progresses rapidly and encompassing a severe acute exacerbation of liver functions.Liver transplantation is the ultimate and effective treatment of HBV-ACLF.The prognosis of HBV-ACLF is poor,as the mortality without LT is more than 70%.While the 1-year survival rate after liver transplantation in some main centers of liver transplantation is more than 80-90%,its limitation lies in the shortage of donor liver.Artificial liver support system can significantly save the function of liver,kidney and coagulation of patients,and reduce the MELD score of patients,reduce the mortality of patients,and effectively prolong the waiting time of liver donor.However,there is still a lack of relevant data on whether perioperative artificial liver support system treatment has an impact on the survival rate of patients after transplantation.The purpose of this study is to explore the effect of non-biological artificial liver therapy before liver transplantation on the operation and prognosis of liver transplantation patients,to explore the prognostic factors,and to evaluate the ability of the commonly used ACLF prognostic model to predict the short-term prognosis after liver transplantation.Methods One hundred and sixty-six patients with HBV-related ACLF received LT in the first affiliated hospital of Zhejiang University school of medicine between January 2011 and December 2018 were included.Of the 166 patients,109 were included in the ALSS+SMT+LT group(observation group),and they received 322 times of PE-centered ALSS treatment before LT,the remaining 57 were in the SMT+LT group(control group),they received emergency LT after standard medical therapy.The general information,clinical indicators and laboratory examination of all patients were recorded.All patients' prognosis were collected by followed up for 4 weeks,12 weeks,48 weeks and 96 weeks after LT.And the risk factors were identified by Cox regression analysis.All datas were statistically analyzed by SPSS22.0 and R V.3.3.2.Results 1.Baseline of patients Compared with the control group,patients in the observation group were younger in age(P <0.05)and had higher ALT,AST,TBil and TBA(P <0.05).There were no significant differences in gender and other laboratory examinations(WBC,N%,Alb,PTA,Cr,Na+,HBV-DNA and NLR)and MELD,CLIF-C-ACLF,CLIF-C OF and COSSH-ACLF scores between the two groups(P>0.05).2.Efficacy of ALSS Before ALSS treatment,109 HBV-ACLF patients in observation group were in poor condition.After ALSS treatment,the liver and kidney function,coagulation function and electrolyte indexes of the patients were significantly improved compared with that before the first treatment of ALSS.The laboratory parameters including ALT,AST,TBil,TBA and INR were significantly lower.PTA,Na+,WBC and N% were significantly higher(p <0.05),HGB and PLT were lower than before ALSS(p<0.05).MELD score and COSSH-ACLF score significantly decreased after ALSS(P<0.001).CLIF-C-ACLF showed the same trend of decrease,but there was no statistical differences(P>0.05).3.Impact of ALSS on waiting time for LT,intraoperative blood loss,ICU staying and in-hospital time after LT.Compared with control group,the waiting time for LT in observation group was significantly prolonged(21.24±21.1 vs 5.23±5.73,P<0.05).Intraoperative blood loss(1306.42±969.56 vs 1843.86±1311.08)and postoperative ICU staying(9.79±5.68 vs 10.73±4.62)were significantly reduced(P <0.05).And there were no significant differences between the two groups in postoperative hospital staying(28.22±12.52 vs 27.61±7.39,P>0.05).4.Impact of ALSS on patients' survival after LT Compared with control group,the 4W-survival rates and 12W-survival rates in observation group were significantly higher(91.7% vs 80.7%,87.2% vs 73.7%,p<0.05).The similar trends were also observed in 48 W and 96W-survival rates in the two groups,but no statistical differences(80.7% vs 72.0%,79.8% vs 70.2%,p >0.05).COX regression analysis of prognostic risk factors in 166 patients showed that ALSS treatment(P=0.035)was an independent factor affecting the survival of HBV-ACLF after LT.5.The value of NLR,COSSH-ACLF,MELD,CLIF-C-ACLF and CLIF-C OFs in predicting 28-day mortality of HBV-ACLF with LT.The NLR showed a significantly higher predictive ability in comparison with all the other scores.The area under the ROC curve of NLR(AUROC:0.882)was higher than that of COSSH-ACLF(AUROC: 0.71,P=0.003),MELD(AUROC: 0.64),CLIF-C-ACLF(AUROC: 0.70)and CLIF-C OFs(AUROC: 0.65).According to the cut-off value,the patients were further divided into the following groups:NLR?8.5,COSSH-ACLF ?6.79,MELD?28,CLIF-C-ACLF?45.87,CLIF-C OFs?10.0,all of which were in the high-mortality group.Conclusions 1.Perioperative ALSS treatment can effectively prolong the waiting time for a donor liver and obviously reduce the short-term(4-weeks and 12-weeks)postoperative mortality.ALSS treatment is related to the prognosis and lower the the risk of short-term death in HBV-ACLF patients.2.Perioperative ALSS treatment can significantly improve the biochemical indicators of HBV-ACLF,reduce MELD,COSSH-ACLF,CLIF-C-ACLF scores,and reduce the amount of blood loss during LT and shorten ICU staying time after LT,which are beneficial to HBV-ACLF's prognosis.3.Basic NLR,MELD,COSSH-ACLF,CLIF-C-ACLF and CLIF-C OFs scores were prognostic factors in patients with HBV-ACLF.And NLR is superior to COSSH-ACLF,MELD,CLIF-C-ACLF and CLIF-OFs in predicting short-term(4-weeks and 12-weeks)mortality after LT.