HUMAN HEPATIC PRENEOPLASIA - PHENOTYPES AND PROLIFERATION KINETICS OFFOCI AND NODULES OF ALTERED HEPATOCYTES AND THEIR RELATIONSHIP TO LIVER-CELL DYSPLASIA

Foci of altered hepatocytes (FAH) represent preneoplastic lesions, as shown in various animal models of hepatocarcinogenesis, but their sign ificance in the human liver has not been established. The cellular com position, size distribution and proliferation kinetics of FAH in 163 e xplanted and resected human livers with or without hepatocellular carc inoma (HCC) and their possible association with small-cell change of h epatocytes (SCC) were therefore studied. FAH, including glycogen-stori ng foci (GSF), mixed cell foci (MCF) and basophilic cell foci, were fo und in 84 of 111 cirrhotic livers, demonstrating higher incidences in cases with (29/32) than in those without HCC (55/79). FAH were observe d more frequently in HCC-free cirrhosis associated with hepatitis B or C virus or chronic alcoholic abuse (high-risk group) (37/47) than in that due to other causes (low-risk group) (12/21). MCF predominant in cirrhotic livers of the high-risk group, were mon proliferative, large r and more often involved in formation of nodules of altered hepatocyt es (39.3%) than were GSF (8.5%). The results suggest that the FAH are preneoplastic lesions, MCF being more advanced than GSF. Oncocytic and amphophilic cell foci were also observed, but their significance rema ins to be clarified. Two types of SCC, namely diffuse and intrafocal S CC, were identified, but only intrafocal SCC was found to be related t o increased proliferative activity and more frequent nodular transform ation of the FAH involved, suggesting a close association with progres sion from FAH to HCC.