Clear mortality gap caused by graft macrosteatosis in Chinese patients after cadaveric liver transplantation

Lyu

et al. 2023

Front. Surg.

Self Cite

AimTo investigate the interactions between the graft-to-recipient weight ratio (GWRWR) and other risk factors responsible for inferior allograft outcomes.MethodsA total of 362 patients who received liver transplantation (LT) were enrolled. Indicators such as graft/recipient weight and other prognostic factors were collected. Comparisons of indicators and survival analysis were performed in groups categorized by the GWRWR. Interactions of large-for-size grafts (LFSGs) with graft macrosteatosis (MaS) were evaluated in terms of relative excess risk caused by interaction (RERI) and attributable proportion (AP). Cytoscape visualized the role of LFSGs in the risk profile for poor prognosis.ResultsBased on the GWRWR, LT cases can be categorized into three subgroups, standard (1%–2.5%), optimal (2.5%–3.0%), and inferior prognosis (>3.0%). Survival analysis confirmed clear separations in cases categorized by the above-defined limits on the GWRWR (P < 0.05). LFSGs caused inferior prognosis by initiating positive interactions with MaS severity.ConclusionThe GWRWR exerted nonlinear effects on prognosis in deceased donor LT cases. LFSGs (GWRWR > 3.0%) caused inferior outcomes, while grafts sized within (2.5%–3.0%) had optimal post-transplant prognosis. MaS increased the risk of poor prognosis by exerting positive synergistic effects on LFSGs.

“…MaS is a well-known risk factor in the LT process ( 6 , 12 ). However, the connection and interactive effects between MaS and graft size have been rarely reported in previous studies.…”

Section: Discussionmentioning

confidence: 99%

“…Macrosteatosis (MaS) was assessed under microscopic observation in a double-blinded manner ( 6 ). Graft failure (GF) and patient death (PD) were the primary endpoints representing the prognosis.…”

Section: Methodsmentioning

confidence: 99%

Graft-to-recipient weight ratio exerts nonlinear effects on prognosis by interacting with donor liver macrosteatosis

Lyu

et al. 2023

Front. Surg.

Self Cite

“…Major complications, including early allograft dysfunction (EAD) and primary nonfunction (PNF), were also assessed in each recipient postoperatively, based on liver and coagulation function tests. More details of the definitions of EAD/PNF have been described previously [ 21 ]. Detailed clinical data and follow-up information for the enrolled cases are shown in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

Integrative Network Analysis Revealed Genetic Impact of Pyruvate Kinase L/R on Hepatocyte Proliferation and Graft Survival after Liver Transplantation

Oxidative Medicine and Cellular Longevity

Zhao

Wang

et al. 2021

Self Cite

Background. Pyruvate kinase L/R (PKLR) has been suggested to affect the proliferation of hepatocytes via regulation of the cell cycle and lipid metabolism. However, its impact on the global metabolome and its clinical implications remain unclear. Aims. We aimed to clarify the genetic impact of PKLR on the metabolomic profiles of hepatoma cells and its potential effects on grafts for liver transplantation (LT). Methods. Nontargeted and targeted metabolomic assays were performed in human hepatoma cells transfected with lentiviral vectors causing PKLR overexpression and silencing, respectively. We then constructed a molecular network based on integrative analysis of transcriptomic and metabolomic data. We also assessed the biological functions of PKLR in the global metabolome in LT grafts in patients via a weighted correlation network model. Results. Multiomic analysis revealed that PKLR perturbations significantly affected the pyruvate, citrate, and glycerophospholipid metabolism pathways, as crucial steps in de novo lipogenesis (DNL). We also confirmed the importance of phosphatidylcholines (PC) and its derivative lyso-PC supply on improved survival of LT grafts in patients. Coexpression analysis revealed beneficial effects of PKLR overexpression on posttransplant prognosis by alleviating arachidonic acid metabolism of the grafts, independent of operational risk factors. Conclusion. This systems-level analysis indicated that PKLR affected hepatoma cell viability via impacts on the whole process of DNL, from glycolysis to final PC synthesis. PKLR also improved prognosis after LT, possibly via its impact on the increased genesis of beneficial glycerophospholipids.

“…31,[37][38][39][42][43][44][45] Based on our previous study, the major peri-operative risk factors for LT were divided into four categories (including recipients, donors, grafts, and surgery). 39,46 We summarized the prior achievements of clinical omics studies that were categorized according to the above-…”

Section: Introductionmentioning

confidence: 99%

Recent Progress and Future Direction for the Application of Multiomics Data in Clinical Liver Transplantation

Que³

et al. 2022

J Clin Transl Hepatol

Self Cite

Omics data address key issues in liver transplantation (LT) as the most effective therapeutic means for end-stage liver disease. The purpose of this study was to review the current application and future direction for omics in LT. We reviewed the use of multiomics to elucidate the pathogenesis leading to LT and prognostication. Future directions with respect to the use of omics in LT are also described based on perspectives of surgeons with experience in omics. Significant molecules were identified and summarized based on omics, with a focus on post-transplant liver fibrosis, early allograft dysfunction, tumor recurrence, and graft failure. We emphasized the importance omics for clinicians who perform LTs and prioritized the directions that should be established. We also outlined the ideal workflow for omics in LT. In step with advances in technology, the quality of omics data can be guaranteed using an improved algorithm at a lower price. Concerns should be addressed on the translational value of omics for better therapeutic effects in patients undergoing LT.