Pathophysiological mechanisms of cell death affecting graft survival in liver transplantation

Figure 1 Sequence of interacting processes occurring in liver transplantation patients. LT: Liver transplantation; AI: Artificial intelligence; NMP: Normothermic macnine perfusion; HIRI: Hepatic ischemia reperfusion injury; SIRS: Systemic inflammatory response syndrome; MODS: Multiple organ dysfunction syndrome; ATP: Adenosine triphosphate; NO: Nitric oxide; ROS: Reactive oxygen species; KC: Kupffer cells; EAD: Early allograft dysfunction; MHC: Major histocompatibility complex.

Figure 2 Cell death mechanisms involved in hepatic ischemia reperfusion injury and liver graft injury. HIRI: Hepatic ischemia reperfusion injury; TNF-R1: TNF-α-receptor; DAMPs: Damage-associated molecular patterns; PRRs: Pattern recognition receptors; TLRs: Toll-like receptors; ROS: Reactive oxygen species; NF-κB: Nuclear factor Κβ; ATG: Autophagy-related proteins; NLRP3: NLR family pyrin domain containing 3; MAPK: Mitogen-activated protein kinase; GPX4: Glutathione peroxidase 4; TRPM2: Transient receptor potential melastatin 2; STAT1/STAT3: Signal transducer and activator of transcription; GSDMD: Gasdermin D; cGAS–STING: Cyclic GMP–AMP synthase; RIPK3: Receptor-interacting protein kinase 3; MLKL: Mixed lineage kinase domain-like protein; TNFRSF: Tumor necrosis factor receptor superfamily; ZBP1: Z-DNA-binding protein 1; NE: Neutrophilic elastase; MPO: Myeloperoxidase; PAD4: Peptidyl-arginine deaminase 4.

Figure 3 Mechanisms of PANoptosis. ZBP1: Z-DNA-binding protein 1; AIM2: Absent in melanoma; NLRP12: NLR family pyrin domain containing 12; NLRP3: NLR family pyrin domain containing 3; RIPK1: Receptor-interacting protein kinase 1; ASC: Apoptosis-associated speck-like protein containing a CARD; FADD: Fas-associated death domain; Casp: Caspase; GSDMD: Gasdermin D; MLKL: Mixed lineage kinase domain-like protein; HIRI: Hepatic ischemia-reperfusion injury; EAD: Early allograft dysfunction; LT: Liver transplantation.

Figure 4 Factors contributing to hepatic ischemia reperfusion injury and graft outcome during liver transplantation. HIRI: Hepatic ischemia reperfusion injury; DCD: Donation after circulatory death; MELD: Model for end-stage liver disease; LSECs: Liver sinusoidal endothelial cells; EAD: Early allograft dysfunction.