1. Figure 5 Hepatic regeneration in ACLF
Figure 5 | Hepatic regeneration in ACLF. Acute hepatic injury, release of endotoxins from gut to the liver, production of DAMPs by ongoing parenchymal and nonparenchymal cell injury, activates Kuppfer cells and macrophages to release IL-6 and TNF. These cytokines act together to perpetuate hepatic injury in chronic liver disease or stable cirrhosis. Regenerative effects of TNF and IL-6 are perturbed in patients with ACLF because of increased myofibroblast-driven tissue scarring, which inhibits hepatocyte self-replication. However, restoration of lost hepatic mass is achieved by the rapid activation and differentiation of HPCs and ductular proliferation. Furthermore, endogenous mobilization of bone marrow derived HSCs, MSCs and possibly EPCs in response to injury, and therapeutic supplementation by exogenous G-CSF or darbopoetin-α, potentiates the recruitment of bone-marrow-derived stem cells to the injured liver. The dotted lines and '?' depict mechanism(s) that are not established or lack direct evidence to date. ACLF, acute-on-chronic liver disease; EPCs, endothelial progenitor cells; G-CSF, granulocyte colony-stimulating factor; Hh, hedgehog; HPC, hepatic progenitor cell; HSCs, haematopoietic stem cells; IH, intermediate hepatocyte; MSCs, mesenchymal stem cells.
Sarin, S. K. & Choudhury, A. (2016) Acute‑on‑chronic liver failure: terminology, mechanisms and management
Nat. Rev. Gastroenterol. Hepatol. doi: /nrgastro