SEQUENTIAL-CHANGES IN HUMAN ITO CELLS AND THEIR RELATION TO POSTNECROTIC LIVER FIBROSIS IN MASSIVE AND SUBMASSIVE HEPATIC-NECROSIS

To examine the relationship of Ito cells to postnecrotic liver fibrosi s, liver specimens, obtained at autopsy from 17 patients with acute ma ssive necrosis (AMN) and acute submassive hepatic necrosis (ASMN), wer e examined immunohistochemically. In normal adult livers, to cells pos itive for a-smooth muscle actin isoform (ASMA) were rarely seen, scatt ered along hepatic sinusoids. In contrast, in AMN the Ito cells in nec rotic areas became strongly positive for ASMA. They were swollen with elongated cytoplasmic processes along collapsed sinusoidal walls. Arou nd these ASMA-positive Ito cells, there were numerous infiltrated macr ophages and lymphocytes present. There was no significant alteration o f fibroblasts in the portal tracts. In the middle and late stages of A SMN, the spindle-shaped ASMA-positive Ito cells formed a continuous ce llular network. New fibre formation was predominantly around them. In this immediate postnecrotic fibrosis, ASMA-positive stromal cells of I to cell origin were distributed irregularly and were closely associate d with reticulin and newly-formed collagen fibres. Regenerative nodule s were surrounded by dense layers of ASMA-positive stromal cells. Thro ughout the stages of ASMN, portal fibroblasts remained negative for AS MA. We believe that Ito cells in necrotic areas show myofibroblastic t ransformation and play a central role in the postnecrotic liver fibros is. Portal fibroblasts play no significant part in this type of fibros is.