Acute liver failure is a rare but catastrophic condition which can progress rapidly to multi-organ failure. Studies investigating the onset of individual organ injury such as the liver, kidneys and brain during the evolution of
acute liver failure, are lacking.
MicroRNAs are short, non-coding strands of
RNA that are released into the circulation following tissue injury. In this study, we have characterised the release of both global
microRNA and specific
microRNA species into the plasma using a porcine model of
acetaminophen-induced
acute liver failure. Pigs were induced to
acute liver failure with oral
acetaminophen over 19h±2h and death occurred 13h±3h thereafter. Global
microRNA concentrations increased 4h prior to
acute liver failure in plasma (P<0.0001) but not in isolated exosomes, and were associated with increasing plasma levels of the damage-associated molecular pattern molecule, genomic
DNA (P<0.0001). MiR122 increased around the time of onset of
acute liver failure (P<0.0001) and was associated with increasing international normalised ratio (P<0.0001). MiR192 increased 8h after
acute liver failure (P<0.0001) and was associated with increasing
creatinine (P<0.0001). The increase in miR124-1 occurred concurrent with the pre-terminal increase in intracranial pressure (P<0.0001) and was associated with decreasing cerebral perfusion pressure (P<0.002). Conclusions:
MicroRNAs were released passively into the circulation in response to
acetaminophen-induced cellular damage. A significant increase in global
microRNA was detectable prior to significant increases in miR122, miR192 and miR124-1, which were associated with clinical evidence of liver, kidney and
brain injury respectively.