Post-transplant infection improves outcome of hepatocellular carcinoma patients after orthotopic liver transplantation

BACKGROUND Tumor recurrence after orthotopic liver transplantation(OLT)remains a serious threat for long-term survival of the recipients with hepatocellular carcinoma(HCC),since very few factors or measures have shown impact on overcoming HCC recurrence after OLT.Postoperative infection suppresses tumor recurrence and improves patient survival in lung cancer and malignant glioma probably via stimulating the immune system.Post-transplant infection(PTI),a common complication,is deemed to be harmful for the liver transplant recipients from a short-term perspective.Nevertheless,whether PTI inhibits HCC recurrence after OLT and prolongs the long-term survival of HCC patients needs to be clarified.AIM To investigate the potential influence of PTI on the survival and tumor recurrence of patients with HCC after OLT.METHODS A total of 238 patients with HCC who underwent OLT between August 2002 and July 2016 at our center were retrospectively included and accordingly subdivided into a PTI group(53 patients)and a non-PTI group(185 patients).Univariate analyses,including the differences of overall survival(OS),recurrence-free survival(RFS),and post-recurrence survival(PRS),between the PTI and non-PTI subgroups as well as survival curve analysis were performed by the Kaplan-Meier method,and the differences were compared using the log rank test.The variables with a P-value<0.1 in univariate analyses were included in the multivariate survival analysis by using a Cox proportional-hazards model.RESULTS The 1-,3-,and 5-year OS and RFS rates of the whole cohort were 86.6%,69.0%,and 63.6%,and 75.7%,60.0%,and 57.3%,respectively.The 1-,3-,and 5-year OS rates for the PTI patient group(96.0%,89.3%,and 74.0%)were significantly higher than those for the non-PTI group(84.0%,63.4%,and 60.2%)(P=0.033).The absence of PTI was an independent risk factor for dismal OS(relative risk[RR]=2.584,95%CI:1.226-5.449)and unfavorable RFS(RR=2.683,95%CI:1.335-5.390).Subgroup analyses revealed that PTI remarkably improved OS(P=0.003)and RFS(P=0.003)rates of HCC patients with vascular invasion(IV),but did not impact on OS(P=0.404)and RFS(P=0.304)of patients without VI.Among the patients who suffered post-transplant tumor recurrence,patients with PTI showed significantly better OS(P=0.026)and PRS(P=0.042)rates than those without PTI.CONCLUSION PTI improves OS and RFS of the transplant HCC patients at a high risk for posttransplant death and tumor recurrence,which is attributed to suppressive effect of PTI on HCC recurrence.

High mortality associated with gram-negative bacterial bloodstream infection in liver transplant recipients undergoing immunosuppression reduction

BACKGROUND Immunosuppression is an important factor in the incidence of infections in transplant recipient.Few studies are available on the management of immunosuppression(IS)treatment in the liver transplant(LT)recipients complicated with infection.The aim of this study is to describe our experience in the management of IS treatment during bacterial bloodstream infection(BSI)in LT recipients and assess the effect of temporary IS withdrawal on 30 d mortality of recipients presenting with severe infection.AIM To assess the effect of temporary IS withdrawal on 30 d mortality of LT recipients presenting with severe infection.METHODS A retrospective study was conducted with patients diagnosed with BSI after LT in the Department of Liver Surgery,Renji Hospital from January 1,2016 through December 31,2017.All recipients diagnosed with BSI after LT were included.Univariate and multivariate Cox regression analysis of risk factors for 30 d mortality was conducted in the LT recipients with Gram-negative bacterial(GNB)infection.RESULTS Seventy-four episodes of BSI were identified in 70 LT recipients,including 45 episodes of Gram-positive bacterial(GPB)infections in 42 patients and 29 episodes of GNB infections in 28 patients.Overall,IS reduction(at least 50%dose reduction or cessation of one or more immunosuppressive agent)was made in 28(41.2%)cases,specifically,in 5(11.9%)cases with GPB infections and 23(82.1%)cases with GNB infections.The 180 d all-cause mortality rate was 18.5%(13/70).The mortality rate in GNB group(39.3%,11/28)was significantly higher than that in GPB group(4.8%,2/42)(P=0.001).All the deaths in GNB group were attributed to worsening infection secondary to IS withdrawal,but the deaths in GPB group were all due to graft-versus-host disease.GNB group was associated with significantly higher incidence of intra-abdominal infection,IS reduction,and complete IS withdrawal than GPB group(P<0.05).Cox regression showed that rejection(adjusted hazard ratio 7.021,P=0.001)and complete IS withdrawal(adjusted hazard ratio 12.65,P=0.019)were independent risk factors for 30 d mortality in patients with GNB infections after LT.CONCLUSION IS reduction is more frequently associated with GNB infection than GPB infection in LT recipients.Complete IS withdrawal should be cautious due to increased risk of mortality in LT recipients complicated with BSI.

Effect of Platelet-derived P-selectin on Neutrophil Recruitment in a Mouse Model of Sepsis-induced Acute Kidney Injury

Background：Acute kidney injury （AKI） is a severe disease in critically ill patients.Neutrophil infiltration into kidney was associated with the development of AKI,and P-selectin may be involved in the process of neutrophil recruitment in kidney.This study aimed to explore the potential effect of platelet-derived P-selectin on neutrophil recruitment in a mouse model of sepsis-induced AKI.Methods：A total of 30 C57BL/6 male mice were divided into five groups （n =6 in each）：sham group,sepsis group,anti-Ly6G group,anti-P-selectin group,and platelet depletion group.Sepsis was induced by cecal ligation and puncture.Serum creatinine concentration and platelet activity were measured by biochemical detector and flow cytometry,respectively.Histological and pathological features were analyzed using hematoxylin-eosin （HE） and immunohistochemi stry （IHC） staining,respectively.Myeloperoxidase （M PO） activity was detected with MPO assay.Unpaired t-test was used for data analysis.Results：Serum creatinine increased significantly in septic group compared to sham group （2.68 ± 0.27 mg/dl vs.0.82 ± 0.19 mg/dl,t =12.06,P =0.0000） but attenuated in antibodies-treated animals compared to septic group （anti-Ly6G：1.62 ± 0.30 mg/dl vs.2.68 ± 0.27 mg/dl,t =5.76,P=0.0004;anti-P-selectin：1.76 ± 0.31 mg/dl vs.2.68 ± 0.27 mg/dl,t =4.92,P =0.0012;and platelet depletion：1.93 ± 0.29 mg/dl vs.2.68 ± 0.27 mg/dl,t =4.14,P =0.0032）.Platelet amount significantly decreased compared to sham group （658.20 ± 60.64 × 109/L vs.822.00 ± 48.60 × 109/L,t =4.71,P =0.0015） in septic mice,especially in platelet depletion group （240.80 ± 44.98 × 109/L vs.822.00 ± 48.60 × 109/L,t =19.63,P =0.0000）.P-selectin activity was significantly increased in septic group compared to sham group （16.54 ± 1.60% vs.1.90 ± 0.29%,t =15.64,P =0.0000） but decreased significantly in platelet depletion group compared to septic group （3.62 ± 0.68% vs.16.54 ± 1.60%,t =12.89,P =0.0002）.IHC analysis shown that neutrophil infiltration increased in septic mice compared to sham group （36.67 ± 3.79% vs.9.17 ± 1.61%,t =11.58,P =0.0003） and function-blocked groups （anti-Ly6G：36.67 ± 3.79% vs.15.33 ± 1.53%,t =9.05,P 0.0008;anti-P-selectin：36.67 ± 3.79% vs.21.33 ± 1.53%,t =6.51,P=0.0029;and platelet depletion：36.67 ± 3.79% vs.23.33 ± 3.06%,t =4.75,P =0.0090）.MPO increased significantly in septic group compared to control （49.73 ± 1.83 ng/mg prot vs.13.04 ± 2.16 ng/mg prot,t =19.03,P =0.0000） but decreased in function-blocked groups compared to septic group （anti-Ly6G：26.52 ± 3.86 ng/mg prot vs.49.73 ± 1.83 ng/mg prot,t =9.59,P =0.0000;anti-P-selectin：33.06 ± 6.75 ng/mg prot vs.49.73 ± 1.83 ng/mg prot,t =4.85,P =0.0013;and platelet depletion：33.37 ± 2.25 ng/mg prot vs.49.73 ± 1.83 ng/mg prot,t =5.33,P =0.0007）.Conclusion：Platelets-derived P-selectin may be involved in the development of septic AKI through inducing neutrophil infiltration into kidney.