Acute Liver Failure

Multimodal decoding of human liver regeneration

“…The major causes of ALF in the UK and the USA are acetaminophen (paracetamol) toxicity, nonA-E hepatitis, ischaemia, drug-induced liver injury, hepatitis B virus, and autoimmunity, with acetaminophen toxicity representing the commonest cause of ALF in the UK (65.4% of cases) and USA (45.7% of cases) 3 . In contrast, viral hepatitis A, B, and E are the main causes of ALF in Asia 6 . In severe cases of ALF, emergency liver transplantation remains the only curative option.…”

“…Here, using a cross-species, integrative multimodal approach, we have investigated the cellular and molecular mechanisms regulating liver regeneration. Our data define: (1) the first singlecell, pan-lineage atlas of human liver regeneration; (2) a novel ANXA2 + migratory hepatocyte subpopulation which emerges during human liver regeneration; (3) a corollary migratory hepatocyte subpopulation in APAP-induced mouse liver injury; (4) that wound closure precedes hepatocyte proliferation during APAP-induced mouse liver injury; (5) motile hepatocytes (assessed using 4-D intravital imaging) at the edge of the necrotic area of APAPinduced mouse liver injury enable collective migration of the hepatocyte sheet to effect wound closure; (6) that depletion of hepatocyte ANXA2 expression reduces hepatocyte growth factor (HGF)-induced human and mouse hepatocyte migration in vitro, and abrogates necrotic wound closure following APAP-induced mouse liver injury.…”