Parenchymal and nonparenchymal cellular responses in human hepatic regeneration

To characterize cellular responses during hepatic regeneration, we examined 13 explant livers and 5 liver allografts by immunohistochemistry for cytok eratin 7, HepPar1, CD68, alpha -smooth muscle actin (alpha -SMA) and prolif erating cell nuclear antigen as well as reticulin and Masson-trichrome stai ning. Within a week after liver damage, elongated CD68-positive cells were detected along the border of necrotic area. The number of alpha -SMA-positi ve cells was slightly increased along the sinusoids. Ductular proliferation or fibrosis was negligible. After one or two weeks, the size and number of CD68-positive cells were markedly increased. alpha -SMA-positive cells inc reased in number within lobules and portal tracts. Ductular proliferation o ccurred predominantly at the limiting plate or along the border of necrotic areas. After one month, necrotic parenchyma was replaced by many ductules, CD68-positive cells, alpha -SMA-positive cells. Nodules of regenerating he patocytes and irregular fibrosis were diffusely present. Other nonparenchym al cells were not significantly changed. These observations indicate that c hronological interaction between nonparenchymal and parenchymal cells occur during the course of human hepatic regeneration and suggest extensive port o-periportal fibrosis more than a few months after the onset of fulminant h epatitis is a major indicator of chronic functional impairment necessitatin g liver transplantation.