Intent‐to‐treat survival in liver transplantation has not improved in 3 decades due to donor shortage relative to waitlist growth

Kwak

et al. 2023

Nat Commun

Decellularized extracellular matrix scaffold, widely utilized for organ engineering, often undergoes matrix decomposition after transplantation and produces byproducts that cause inflammation, leading to clinical failure. Here we propose a strategy using nano-graphene oxide to modify the biophysical properties of decellularized liver scaffolds. Notably, we demonstrate that scaffolds crosslinked with nano-graphene oxide show high resistance to enzymatic degradation via direct inhibition of matrix metalloproteinase activity and increased mechanical rigidity. We find that M2-like macrophage polarization is promoted within the crosslinked scaffolds, which reduces graft-elicited inflammation. Moreover, we show that low activities of matrix metalloproteinases, attributed to both nano-graphene oxide and tissue inhibitors of metalloproteinases expressed by M2c, can protect the crosslinked scaffolds against in vivo degradation. Lastly, we demonstrate that bioengineered livers fabricated with the crosslinked scaffolds remain functional, thereby effectively regenerating damaged livers after transplantation into liver failure mouse models. Overall, nano-graphene oxide crosslinking prolongs allograft survival and ultimately improves therapeutic effects of bioengineered livers, which offer an alternative for donor organs.

Section: Introductionmentioning

confidence: 99%

Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation

Kwak

et al. 2023

Nat Commun

“…The success of liver transplantation (LT) in the treatment of end-stage liver failure has resulted in an important imbalance between the numbers of patients on the waiting list and donor organ availability [ 1 ]. To overcome this imbalance, transplant clinicians are accepting more high-risk liver grafts from extended criteria donors, presenting characteristics such as advanced age or hepatic steatosis, as well as donation after circulatory death (DCD) donors, which are exposed to a period of warm ischemia (WI) prior to procurement, aggravating subsequent ischemia-reperfusion injury (IRI) [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

The Distinct Innate Immune Response of Warm Ischemic Injured Livers during Continuous Normothermic Machine Perfusion

Blondeel

Gilbo

Heedfeld

et al. 2023

IJMS

Although normothermic machine perfusion (NMP) provides superior preservation of liver grafts compared to static cold storage and allows for viability testing of high-risk grafts, its effect on the liver immune compartment remains unclear. We investigated the innate immune response during 6 h of continuous NMP (cNMP) of livers that were directly procured (DP, n = 5) or procured after 60 min warm ischemia (WI, n = 5), followed by 12 h of whole blood (WB) reperfusion. WI livers showed elevated transaminase levels during cNMP but not after WB reperfusion. Perfusate concentrations of TNF-α were lower in WI livers during cNMP and WB reperfusion, whereas IL-8 concentrations did not differ significantly. TGF-β concentrations were higher in WI livers during NMP but not after WB reperfusion, whereas IL-10 concentrations were similar. Endoplasmic stress and apoptotic signaling were increased in WI livers during cNMP but not after WB reperfusion. Additionally, neutrophil mobilization increased to a significantly lesser extent in WI livers at the end of NMP. In conclusion, WI livers exhibit a distinct innate immune response during cNMP compared to DP livers. The cytokine profile shifted towards an anti-inflammatory phenotype during cNMP and WB reperfusion, and pro-apoptotic signaling was stronger during cNMP. During WB reperfusion, livers exhibited a blunted cytokine release, regardless of ischemic damage, supporting the potential reconditioning effect of cNMP.

“…Since the first case of liver transplantation (LT) in 1963, there has been huge progress that has dramatically increased in the 1-year LT survival rates from 86% in the 1980s to 93% in 2016 (Dunson et al, 2021). Liver transplantation remains a therapeutic option for many patients with liver cirrhosis, hepatocellular carcinoma and treatment-refractory end-stage liver disease (Samuel & Coilly, 2018).…”

Section: Introductionmentioning

confidence: 99%

Concept and risk factors of alcohol relapse in liver transplant recipients with alcohol‐related aetiologies: A scoping review

Jang

Int J Mental Health Nurs

2023

Alcohol relapse in those who received liver transplantation (LT) for alcohol‐related liver disease can lead to poor graft function, low medication adherence rates and decreased chances of survival. Numerous studies have evaluated on this topic; however, discrepancies in the meaning and measurement of ‘alcohol relapse’ lead to heterogeneous results. This scoping review aimed to explore the conceptual and operational definitions of alcohol relapse in LT recipients with alcohol‐related aetiologies and to examine newly reported risk factors of alcohol relapse. Following the Arksey and O'Malley scoping review method and PRISMA guidelines, structured searches for articles published from 2012 to 2022 were conducted in PubMed, CINAHL, Embase, Cochrane and PsycINFO. Twenty‐eight studies were included in the final review. Alcohol relapse was either defined as ‘any alcohol consumption’ or ‘a certain degree of alcohol drinking’ after transplantation. Discrepancies in the incidence rates persisted even within studies that shared the same conceptual definition. Commonly reported risk factors for alcohol relapse were younger age, social isolation and shorter abstinence periods before LT. Self‐efficacy and post‐transplant complications were newly identified risk factors in recent studies; whereas environmental factors such as external stressors were rarely included. The variance in the definition of alcohol relapse and inconsistent identification methods make it difficult to organize a structured interventional study. A standardized stratification of post‐LT alcohol relapse behaviour is needed to prior to implementing interventions that employ a harm minimization approach. Cost‐effective interventions promoting self‐efficacy could enable the prevention and management of alcohol relapse after LT.