Acute Rejectionin Recipients Undergoing Living Donor Or Donation After Circulatory Death Liver Transplantation

Background and aim:Liver transplantation is the only effective way to treat end-stage liver disease.With the rapid increase in the number of patients waiting for liver transplantation,the shortage of donor liver has become a bottleneck restricting the development of liver transplantation.Living donor liver transplantation(LDLT)and donation after circulatory death(DCD)expanded the donor pool,alleviating the contradiction of donor liver deficiency.However,there are still some complications after liver transplantation seriously affect the prognosis of liver transplant recipients.Acute rejection(AR)is one of the most common complications after liver transplantation,which is an important factor affecting the prognosis of liver transplantation.This study enrolled 152 cases of LDLT and 436 cases of DCD liver transplantation of the First Affiliated Hospital,Zhejiang University School of Medicine.The purpose of this study was to evaluate the incidence and risk factors of AR,furthermore,to identify significant prognostic factors that can influence post-transplant survival in LDLT and DCD liver transplantation recipients.Thus it can help us to find out strategies to improve the prognosis of LDLT and DCD liver transplantation.Methods:The recipients underwent LDLT and DCD liver transplantation were retrospectively reviewed from June 2001 to June 2016 at the First Affiliated Hospital,Zhejiang University School of Medicine.The following characteristics were collected for each recipient:Age,gender,primary liver diseases,body mass index(BMI),cold ischemia time,warm ischemia time,blood loss,RBC transfusion,graft-to-recipient weight ratio,operation time.The pre-transplant data were collected within 24-hour before liver transplantation.The serum creatinine and total bilirubin were also collected at 24-hour after liver transplantation to calculated the PMPM score which was described by our previous study to predict shortand medium-term mortality in liver transplant recipients.PMPM score =-5.359+1.988*ln(serum creatinine[mg/dl])+1.089*ln(total bilirubin[mg/dl]).The recipients were divided into LDLT group(n=152)and DCD liver transplantation group(DCD group,n=436).The 152 cases of LDLT recipients were divided into acute rejection group(LAR group)and non-acute rejection group(LNAR group)according to the acute rejection statue.Then the 436 cases of DCD recipients were divided into acute rejection group(DAR group)and non-acute rejection group(DNAR group).The clinical data of these groups were compared.The statistical analysis was performed using the statistical software IBM SPSS software(Ver.19.0;SPSS Inc,Chicago,IL,USA).The medians and ranges of continuous data were compared using the Wilcoxon rank sum test.Categorical data were compared using the Pearson chi-squared test or the Fisher exact test,as appropriate.P values less than 0.05 were considered statistically significant.To identify risk factors for AR,a multivariate analysis was performed using the logistic regression model with backward elimination.Overall survival(OS)was defined as the time span from initial diagnosis until death from any cause or last known contact.OS analysis was performed by Kaplan-Meier methodology with log rank testing.Cox proportional hazard models were used to estimate hazard ratios for OS,and to determine independent risk factors.All tests were two-sided,with a P value of<0.05 considered statistically significant.Results:The follow-up time of LDLT group and DCD group was 78.8±3.1 months and 25.0±0.8 months(P=0.000).Of the 152 LDLT recipients,25 cases had AR,the incidence of AR was 16.4%.Of the Of the 436 recipients with DCD liver transplantation,46 recipients had AR,the incidence of AR was 10.6%,and there was no significant difference in the incidence of AR between LDLT group and DCD group(P =0.061).Most of the acute rejection occurred within 1 year after liver transplantation,and there was no significant difference between the two groups(P = 0.256).The average age of 152 LDLT recipients was 43.6 years(16-65 years),of whom 26 were female recipients.The primary disease distribution of 152 recipients was hepatitis B virus(n = 127),hepatocellular carcinoma(n = 47),alcoholic liver disease(n = 6),autoimmune liver disease(n = 5),secondary biliary cirrhosis(n=5),drug-induced liver injury(n=4),cholangiocarcinoma(n=1),hepatitis E virus(n=1),metabolic liver disease(n=1)and others(n=2).Among the 25 LDLT recipients with AR,10 of the AR occurred within 1 month after transplantation and 13 occurred within 6 months after transplantation.The mean time to AR was 158 days(3-1975 days).Univariate analysis of LDLT-related clinical factors showed the proportion of PMPM score>-1.4 in the LAR group was significantly higher than that in the LNAR recipients(16%vs.3.1%,P = 0.026).There was no significant difference of recipient age(41.1 ±2.3 vs.46.1±1.1,P=0.06)and MELD score(22.6 ± 2.1 vs.19.1 ± 0.8,P=0.085)between the two groups.All the P<0.1 factors were entered into multivariate logistic regression.Eventually,a higher PMPM score(odds ratio[OR],5.857;P = 0.018)is identified as independent predictor of AR after LDLT.There was no significant difference in the 1-year,3-year and 5-year survival rates between LAR and LNAR group.The most common cause of death was HCC recurrence(n=12),followed by multiple organ dysfunction syndrome(MODS)(n=3),cardiovascular disease(n=2),bleeding(n=2),sepsis(n=1)and others(n=12).The average age of 436 DCD recipients was 49.4 years(19-74 years),of whom 61 were female recipients.The primary disease distribution of 436 recipients was hepatitis B virus(n = 369),hepatocellular carcinoma(n = 187),alcoholic liver disease(n = 20),autoimmune liver disease(n = 17),metabolic liver disease(n=8),cryptogenic cirrhosis(n=6),secondary biliary cirrhosis(n=6),cholangiocarcinoma(n=6),cholangiocarcinoma(n=1),schistosomiasis liver disease(n=4),drug-induced liver injury(n=3),hepatitis C virus(n = 3),hepatitis E virus(n =2),biliary atresia(n=1)and others(n=2).Among the 46 DCD recipients with AR,20 of the AR occurred within 1 month after transplantation and 31 occurred within 6 months after transplantation.The mean time to AR was 40 days(5-1134 days).The proportion of recipients’ age≤42(28.0%vs.23.1%,P = 0.046),the female recipients(28.3%vs.12.3%,P = 0.006)and the ratio of biliary atresia(2.2%vs.0,P =0.003)in DAR group were significantly higher than those of DNAR recipients.All the P<0.05 factors were entered into multivariate logistic regression.Eventually,the female recipient(odds ratio[OR],2.989;P = 0.003)and recipient age ≤42(odds ratio[OR],2.097;P = 0.027)were identified as independent predictors of AR after DCD liver transplantation.There was no significant difference in the 1-year,3-year and 5-year survival rates between DAR and DNAR.The most common cause of death was HCC recurrence(n=49),followed by multiple organ dysfunction syndrome(MODS)(n=17),respiratory complications(n=4),abdominal abscess(n=3),cardiovascular disease(n=2),bleeding(n=1)and others(n=1).There was no significant difference in the 1-year,3-year and 5-year survival rates between the DCD group and the LDLT group.We evaluated factors that influenced the overall survival.In the univariate analysis,The recipient age≥60(P=0.001),donor age≥50(P=0.046),HBV infection recipients(P=0.013),HCC recipients(P=0.000),recipient ABO-incompatible(P=0.030)and blood loss(ml/kg)≥21(P=0.007)were significantly associated with recipient overall survival rate.Factors associated with a P-value<0.05 in the univariate analysis were entered into a multivariate analysis using Cox regression.In the multivariate analysis,donor age≥50(odds ratio[OR],1.564;P = 0.002),recipient ABO-incompatible(odds ratio[OR],1.534;P = 0.001)and blood loss(ml/kg)≥21(odds ratio[OR],1.277;P = 0.030)are independent prognostic factors for overall survival after liver transplantation.Conclusions:Higher PMPM score is associated with acute rejection after LDLT.The female recipient and recipient age ≤42 are identified as independent predictors of AR after DCD liver transplantation.Donor age≥50,recipient ABO-incompatible and blood loss(ml/kg)>21 are independent prognostic factors for overall survival after liver transplantation.AR does not affect the long-term outcomes of LDLT and DCD liver transplantation.