Application of ischaemia-free liver transplantation improves prognosis of patients with steatotic donor livers - a retrospective study.

The use of steatotic livers in liver transplantation (LT) is controversial. Ischaemia-free liver transplantation (IFLT) has obvious advantages for the recovery of allograft function. The aim of this study was to examine the effect of liver grafts with steatosis on outcome and the effect of IFLT with steatotic livers. 360 patients with LT were enrolled in this study. Perioperative characteristics and differences in outcome among different grades of steatotic groups, and between the IFLT and conventional LT (CLT) groups were analysed. Occurrence of early allograft dysfunction (EAD; 50%) and primary nonfunction (PNF; 20%) was significantly higher in the severe steatosis group (P < 0.001 and <0.001, respectively). Survival rate is significantly low in severe steatosis group (3-year: 60%, P = 0.0039). The IFLT group had a significantly lower occurrence of EAD than the CLT group (0% vs. 60%, P = 0.01). The level of postoperative peak AST, GGT and creatine were significantly lower in IFLT group (P = 0.009, 0.032 and 0.024, respectively). In multivariable analysis, IFLT and EAD were independent factors affecting postoperative survival. Severe steatotic livers lead to severe complications and poor outcomes in LT. IFLT has obvious advantages for reducing the rate of EAD in LT with steatotic livers.

Utilization of hepatitis B surface antigen-positive donors in liver transplantation for recipients with hepatocellular carcinoma: a retrospective and propensity score matching analysis.

Introduction: The use of extended criteria donor (ECD) grafts such as donor with infection of hepatitis B virus (HBV) is a potential solution for organ shortage. In this study, we aimed to evaluate the safety and long-term survival of utilization of hepatitis B surface antigen-positive (HBsAg+) donor livers in HCC patients using propensity score matching (PSM) analysis. Methods: Forty-eight donors with HBsAg-positive and 279 donors with HBsAg-negative were transplanted and enrolled in this study. PSM analysis were used to eliminate selection bias. Perioperative data and survival were collected and analyzed. Results: PSM generated 44 patient pairs. When comparing intra- and post-operative data, no significant difference was found between groups (P > 0.05). Patients with a HBsAg-positive donor had significantly worse progression-free survival (1-year: 65.9% vs. 90.9%; 3-year: 18.1% vs. 70.4%, P = 0.0060) and overall survival (1-year: 84.1% and 95.4%; 3-year: 27.2% vs. 79.5%, P = 0.0039). In multivariate analysis, donor HBsAg-positivity was an independent risk factor for survival and occurrence (P = 0.005 and 0.025, respectively). Conclusion: In conclusion, with adequate antiviral prophylaxis and treatment, utilization of HBsAg positive liver grafts did not increase the incidence of early-stage complications. However, patient with an HBsAg-positive graft had poorer progression-free survival and overall survival.

Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice.

Background: T cell-mediated acute rejection(AR) after heart transplantation(HT) ultimately results in graft failure and is a common indication for secondary transplantation. It's a serious threat to heart transplant recipients. This study aimed to explore the novel lncRNA-miRNA-mRNA networks that contributed to AR in a mouse heart transplantation model. Methods: The donor heart from Babl/C mice was transplanted to C57BL/6 mice with heterotopic implantation to the abdominal cavity. The control group was syngeneic heart transplantation with the same kind of mice donor. The whole-transcriptome sequencing was performed to obtain differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in mouse heart allograft. The biological functions of ceRNA networks was analyzed by GO and KEGG enrichment. Differentially expressed ceRNA involved in programmed cell death were further verified with qRT-PCR testing. Results: Lots of DEmRNAs, DEmiRNAs and DElncRNAs were identified in acute rejection and control after heart transplantation, including up-regulated 4754 DEmRNAs, 1634 DElncRNAs, 182 DEmiRNAs, and down-regulated 4365 DEmRNAs, 1761 DElncRNAs, 132 DEmiRNAs. Based on the ceRNA theory, lncRNA-miRNA-mRNA regulatory networks were constructed in allograft acute rejection response. The functional enrichment analysis indicate that the down-regulated mRNAs are mainly involved in cardiac muscle cell contraction, potassium channel activity, etc. and the up-regulated mRNAs are mainly involved in T cell differentiation and mononuclear cell migration, etc. The KEGG pathway enrichment analysis showed that the down-regulated DEmRNAs were mainly enriched in adrenergic signaling, axon guidance, calcium signaling pathway, etc. The up-regulated DEmRNAs were enriched in the adhesion function, chemokine signaling pathway, apoptosis, etc. Four lncRNA-mediated ceRNA regulatory pathways, Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox, 1700071M16Rik/miR-145a-3p/Themis2, were finally validated. In addition, increased expression of PVT1, 1700071M16Rik, Tox and Themis2 may be considered as potential diagnostic gene biomarkers in AR. Conclusion: We speculated that Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox and 1700071M16Rik/miR-145a-3p/Themis2 interaction pairs may serve as potential biomarkers in AR after HT.

Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Uremia, and Insulin-Dependent Diabetes.

BACKGROUND Abdominal organ cluster transplantation for the treatment of upper abdominal end-stage diseases is a serious conundrum for surgeons. CASE REPORT We performed clinical assessment of quadruple organ transplantation (liver, pancreas, duodenum, and kidney) for a patient with end-stage liver disease, post-chronic hepatitis B cirrhosis, uremia, and insulin-dependent diabetes mellitus, and explored the optimal surgical procedure. Simultaneous classic orthotopic liver, pancreas-duodenum, and heterotopic renal transplantation was performed on a 46-year-old man. The process was an improvement of surgery implemented with a single vascular anastomosis (Y graft of the superior mesenteric artery and the celiac artery open together in the common iliac artery). The pancreatic secretions and bile were drained through a modified uncut jejunal loop anastomosis, and the donor's kidneys were placed in the right iliac fossa. The patient was prescribed basiliximab, glucocorticoid, tacrolimus, and mycophenolate mofetil for immunosuppression. The hepatic function recovered satisfactorily on postoperative day (POD) 3, and pancreatic function recovered satisfactorily in postoperative month (POM) 1. Hydronephrosis occurred in the transplanted kidney, with elevated creatinine on POD 15. Consequently, renal pelvic puncture and drainage were performed. His creatinine dropped to a normal level on POD 42. No allograft rejections or other complications, like pancreatic leakage, thrombosis, or localized infections, occurred. The patient had normal liver, renal, and pancreas functions with insulin-independent after POD 365. CONCLUSIONS Simultaneous classic orthotopic liver, pancreas-duodenum, and heterotopic renal transplantation is a promising therapeutic option for patients with insulin-dependent diabetes combined with end-stage hepatic and renal disease, and our center's experience can provide a reference for clinical multiorgan transplantation.

T cell proliferation-related genes: Predicting prognosis, identifying the cold and hot tumors, and guiding treatment in clear cell renal cell carcinoma.

Background: Immunotherapy has become a new direction of current research because the effect of traditional radiotherapy and chemotherapy on clear cell renal cell carcinoma (ccRCC) is not satisfactory. T cell proliferation-related genes (TRGs) play a pivotal role in tumor progression by regulating the proliferation, activity, and function of immune cells. The purpose of our study is to construct and verify a prognostic model based on TRGs and to identify tumor subtypes that may guide treatment through comprehensive bioinformatics analyses. Methods: RNA sequencing data, clinical information, and somatic mutation data of ccRCC are obtained from The Cancer Genome Atlas (TCGA) database. We identified the prognosis-related TRGs which were differentially expressed between normal and tumor tissues. After dividing the patients into a train set and a test set according to proportion 1:1 randomly, the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were performed to construct a risk-stratified model. Its prediction performance was verified. Then, Gene Set Enrichment Analysis (GSEA), principal component analysis (PCA), tumor microenvironment (TME) analysis, and the half-maximal inhibitory concentration (IC50) prediction were performed between the different groups of patients. To further discuss the immunotherapy between hot and cold tumors, we divided all patients into two clusters based on TRGs through unsupervised learning. Analyzing the gene mutation and calculating the tumor mutation burden (TMB), we further explored the relationship between somatic mutations and grouping or clustering. Results: Risk-stratified model and nomogram predict the prognosis of ccRCC patients accurately. Functional enrichment analyses suggested that TRGs mainly focused on the biological pathways related to tumor progression and immune response. Different tumor microenvironment, drug resistance, and TMB can be distinguished clearly according to both risk stratification and tumor subtype clustering. Conclusion: In this study, a new stratification model of ccRCC based on TRGs was established, which can accurately predict the prognosis of patients. IC50 prediction may guide the application of anti-tumor drugs. The distinction between hot and cold tumors provides a reference for clinical immunotherapy.

Transplantation of Extended Criteria Donor Livers Following Continuous Normothermic Machine Perfusion Without Recooling.

BACKGROUND: Traditional liver transplant strategies with cold preservation usually result in ischemia-reperfusion injury (IRI) to the donor liver. Regular normothermic machine perfusion (NMP) donor livers suffer IRI twice. Here, we aimed to introduce a novel technique called continuous NMP without recooling to avoid a second IRI and its application in livers from extended criteria donors. METHODS: Seven donor livers transplanted following continuous NMP without recooling, 7 donor livers transplanted following standard NMP, and 14 livers under static cold storage (SCS) were included in this study. Perioperative outcomes were recorded and analyzed between groups. RESULTS: During the NMP without a recooling procedure, all livers cleared lactate quickly to normal levels in a median time of 100 min (interquartile range, 60-180) and remained stable until the end of perfusion. In the NMP without recooling and standard NMP groups, posttransplant peak aspartate aminotransferase and alanine aminotransferase levels were both significantly lower than those in the SCS group (P = 0.0015 and 0.016, respectively). The occurrence rate of early allograft dysfunction was significantly lower in the NMP without recooling group than in the SCS group (P = 0.022), whereas there was no difference in the NMP group with or without recooling (P = 0.462). CONCLUSIONS: Our pilot study revealed a novel technique designed to avoid secondary IRI. This novel technique is shown to have at least a comparable effect on the standard NMP, although more data are needed to show its superiority in the future.

Application of various surgical techniques in liver transplantation: a retrospective study.

BACKGROUND: Surgical techniques of liver transplantation have continually evolved and have been modified. We retrospectively analyzed a single-center case series and compared the advantages and disadvantages of each method. METHODS: Six-hundred and seventy-four recipients' perioperative data were assessed and analyzed stratified by different surgical technics [modified classic (MC), modified piggyback (MPB) and classic piggyback (CPB)]. RESULTS: MELD score and Child-Pugh scores was significantly higher in CPB groups (P=0.008 and 0.003, respectively). Anhepatic time in MPB group was longer than those in CPB group (P<0.05). The operation duration in MPB group was significantly longer than those in MC group and CPB group (P=0.003). Three patients had outflow obstruction (P=0.035). The overall survival in MPB group were better than those in MC group and CPB group in general comparison (P<0.001). In patients with preoperative creatine >120 µmol/L, the overall survival in MC group was worst (P<0.001). In patients with a high MELD score (>24), the overall survival in MPB group tended to be the best (P<0.001). CONCLUSIONS: The advantages and disadvantages are different for these three surgical techniques. A reasonable operation technique should be adopted considering the patient's unique condition to ensure the stability of hemodynamics.

Circulating Tumor Cell Is a Clinical Indicator of Pretransplant Radiofrequency Ablation for Patients with Hepatocellular Carcinoma.

INTRODUCTION: It is of great significance to confirm reliable indicators for the guidance of pretransplant radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). In this study, we aim to investigate whether circulating tumor cell (CTC) status is a clinical indicator for RFA before liver transplantation (LT) in HCC patients. METHOD: CTC analyses were measured in 79 HCC patients. Clinical outcomes including progression-free (PFS) and overall survival (OS) were compared and analyzed between patients with and without pretransplant RFA. RESULT: Forty-two patients were detected as CTC-positive and 18 patients received pretransplant RFA. Recurrence was correlated with CTC count (P=0.024), tumor number (P=0.035), liver cirrhosis (P=0.001), Milan criteria (P=0.003), and University of California San Francisco (UCSF) criteria (P=0.001). Kaplan-Meier analysis revealed that patients with CTC-positive had a lower PFS rate (P=0.0257). For CTC-positive patients, the PFS rate of the pretransplant RFA group was significantly higher than the non-pretransplant RFA group (100% vs. 46.7%, P=0.0236). For CTC-negative patients, both PFS rate and OS rate were similar and without significant differences. In multivariate analysis, pretransplant RFA was the independent factor for PFS (P=0.025). CONCLUSION: Pretransplant CTC status can guide the administration of pretransplant RFA in HCC patients which can improve PFS in CTC-positive HCC patients.

Prognosis after liver transplantation in patients treated with anti-PD-1 immunotherapy for advanced hepatocellular carcinoma: case series.

BACKGROUND: Programmed death protein-1 (PD-1) inhibitors and liver transplantation (LT) are alternative treatments for hepatocellular carcinoma (HCC) patients. The application of PD-1 inhibitors for HCC therapy increases T cell immune activity, while immunosuppression is required for patients receiving transplantation. More clinical investigation is required to determine methods to balance these treatment effects. In this article, we are the first to describe the clinical characteristics, imaging findings, and outcomes of 5 LT patients who had a history of HCC and received anti-PD-1 therapy. METHODS: Data from 5 patients who were diagnosed with HCC and received LT after PD-1 inhibition were analyzed. The doses and courses of PD-1 and preoperative and postoperative characteristics were compared and analyzed. RESULTS: The mean interval between PD-1 inhibition and LT was 63.80±18.26 days. One patient experienced recurrence in the liver, vertebrae and lungs after 7 months, and 1 patient experienced recurrence in the lungs after 3 months. All patients displayed normal liver function at the latest follow-up visit. No acute allograft rejections occurred in any patient. CONCLUSIONS: PD-1 inhibitors may be safe for the treatment of HCC before LT when the interval between the two treatments is sufficient. Further investigations are needed for to validate these findings.

Continuous Normothermic Machine Perfusion for Renovation of Extended Criteria Donor Livers Without Recooling in Liver Transplantation: A Pilot Experience.

Background: Ischemia injury affects the recovery of liver allograft function. We propose a novel technique aimed at avoiding a second ischemic injury: transplanting an extended criteria donor (ECD) liver directly under normothermic machine perfusion (NMP) without recooling. We studied two cases to evaluate the efficacy and safety of this technique. Methods: The perioperative characteristics and postoperative outcomes of two recipients of ECD livers were analyzed. Both transplantations were performed with continuous normothermic machine perfusion without recooling. Result: In case 1, the cause of donor death was anoxia, and the donor liver had hypernatremia before procurement. The recipient was diagnosed with decompensated cirrhosis. His model for end-stage liver disease (MELD) score was 38. In case 2, the donor liver was from a donor after cardiac death (DCD), and the donor had elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. The recipient was diagnosed with acute hepatic failure. His MELD score was 35. Both donor livers were maintained under NMP and then transplanted without recooling. The peak ALT and AST levels after surgery were 452 and 770 U/L in case 1 and 100 and 592 U/L in case 2. Neither early allograft dysfunction (EAD) nor primary graft non-function (PNF) was present in these two cases. Conclusion: In conclusion, our results demonstrate that continuous NMP without recooling is efficacious and safe for LT with extended criteria donor livers. Further investigations of this technique will be performed to confirm these promising results.

A traditional Chinese medicine therapy for coronary heart disease after percutaneous coronary intervention: a meta-analysis of randomized, double-blind, placebo-controlled trials.

Huoxue Huayu therapy (HXHY) has been widely used to treat cardiovascular diseases in traditional Chinese medicine (TCM) such as hypertension and coronary heart disease (CHD). The present study describes a meta-analysis of a series of prospective randomized, double-blind, placebo-controlled trials conducted to evaluate the effect of HXHY on patients with CHD after percutaneous coronary intervention (PCI). The Cochrane Library, PubMed, EMBASE, the China National Knowledge Infrastructure (CNKI), the Chinese Biomedical Literature database, and the Wanfang database were searched up until June 2018. A series of randomized controlled clinical trials were included and the subjects were patients with CHD who had undergone PCI. The experimental group was treated with HXHY therapy, and the control group was treated with placebo; meanwhile, all the patients accepted conventional Western medicine. Review Manager 5.3 software was used for the statistical analysis. Ten trials were included in the final study. The overall risk of bias assessment was low. HXHY had a greater beneficial effect on reducing the in-stent restenosis (ISR) rate (RR = 0.57, 95% confidence interval [CI] [0.40-0.80], P=0.001) and the degree of restenosis (MD = -8.89, 95% CI [-10.62 to -7.17], P<0.00001) compared with Placebo. Moreover, HXHY was determined to be more effective in improving Seattle Angina Questionnaires (SAQ) and the revascularization rate (RR = 0.54, 95% CI [0.32-0.90], P=0.02) compared with Placebo, whereas the rate of death and MI of patients treated with HXHY were no different from those treated with the placebo (P>0.05). Therefore, HXHY is an effective and safe therapy for CHD patients after PCI.