Figure 2.

Proposed model of liver injury progression in indeterminate pediatric acute liver failure.

Systemic inflammatory insults may lead to local liver inflammation in conjunction with exogenous local triggers such as viruses that contain PAMPs, and endogenous local triggers in the form of DAMPS generated from liver injury itself. The release of DAMPS from liver injury may promote a feed forward cycle of inflammation. This liver injury ultimately results in the production of sdf1 to promote the recruitment of sprocs and subsequent liver regenerative programs including HGF. As sprocs arise from the bone marrow, systemic inflammation may inhibit this process via suppression of bone marrow stem cells. Altered metabolic state in the form serum glucose may also provide additional signals to promote hepatic regeneration. Brain injury may result from systemic inflammation itself, compounded by toxic metabolite build up from liver injury and altered metabolic state. Together this network of events may lead to the liver, bone marrow, and brain injury often seen in iPALF.

Footnote for Figure 2: pathogen associated molecular patterns (PAMPs), damage associated molecular patterns (DAMPs), sinusoidal endothelial cell PROgenitor cells (sprocs); stromal cell-derived factor 1 (sdf1), hepatocyte growth factor (HGF), indeterminate Pediatric Acute Liver Failure (iPALF), cytokeratin 7 positive (CK7⁺), cytokeratin 19 positive (CK19⁺), hepatic progenitor cell (HPC).