Human liver regeneration following massive hepatic necrosis - two distinct patterns.

BACKGROUND AND AIM: Massive hepatic necrosis (MHN) is a rare but often fatal complication of various liver injuries. Nevertheless, some patients can survive by spontaneous hepatic regeneration. It is known that surviving hepatocytes and/or progenitor cells can participate in this process but the mechanism of hepatic recovery is vague.

METHODS: We examined thirteen explanted human livers removed for acute liver failure. Combined immunohistochemistry, digital image analysis and 3D reconstruction of serial sections were applied.

RESULTS: Two patterns of regeneration could be distinguished. In livers with centrilobular necrosis, the surviving injured periportal hepatocytes started to proliferate and arrange into acinar structures and expressed AFP. If the injury wiped out almost all hepatocytes, large areas of parenchymal loss were invaded by an intense ductular reaction. The cells at the distal pole of the ductules differentiated into hepatocytes and formed foci organized by the branches of the portal vein. The expanding foci often containing complete portal triads were arranged around surviving central veins. Their fusion eventually could be an attempt to re-establish the hepatic lobules.

CONCLUSIONS: Regeneration of human livers following massive hepatic necrosis can occur in two ways - either through proliferation of AFP positive acinary arranged hepatocytes, or through ductular progenitor cells, with the latter being less efficient. Further investigation of these regenerative pathways may help identify biomarkers for likelihood of complete regeneration, and hence have therapeutic implications.