The morphogenesis of hepatocytes after massive hepatic necrosis to recovery
through liver cell regeneration has not been fully understood. Sequential
biopsies were performed on the native liver of a 22-year old man who underw
ent auxiliary partial orthotopic liver transplantation 1 month after fulmin
ant hepatitis. Auxiliary partial orthotopic liver transplantation was succe
ssful, and the biopsy samples permitted us to examine the regenerating proc
ess of hepatocytes after massive necrosis. At the time of auxiliary partial
orthotopic liver transplantation (postoperative day 0), 95% of hepatocytes
were lost and a few ductules were found in the portal areas. The ductules
stained with cytokeratin 19. At postoperative day 7, the ductules began to
increase in size and number and became dilated over a period of 1 month, wh
en individual hepatocytes with clear cytoplasm appeared from ductules. As t
he differentiation of hepatocytes increased the expression of cytokeratin 1
9 was found to decrease. From 2 to 3 months, all of the ductules were trans
formed into hepatocytes, and they began to form round clusters. From 3 to 6
months, the round cell clusters became organized into trabecula with fibro
sis. From 6 to 12 months, a lobular architecture was established, and by 14
months, the necrotic liver was fully recovered to normal. This study by ex
amination of sequential biopsies demonstrates the progression of the regene
rating profess from total hepatic necrosis to complete recovery.