Relevance of hepatic preneoplasia for human hepatocarcinogenesis

Different lesions have been suggested to represent preneoplastic conditions in human liver. They include liver cell dysplasia, separated in large-cell change (LCC) and small-cell change (SCC), adenomatoid hyperplasia, and the more recently identified foci of altered hepatocytes (FAH) and nodules of altered hepatocytes (NAH). FAH have been demonstrated to represent preneoplastic lesions in various animal models of hepatocarcinogenesis. To demonstrate prevalence and significance of FAH in the human liver, the cellular composition, size distribution, and proliferation kinetics of these lesions were studied in 163 explanted and resected human livers with or without hepatocellular carcinoma (HCC). FAH including glycogen-storing foci (GSF), mixed cell foci (MCF), and basophilic cell foci were found in 84 of 111 cirrhotic livers, demonstrating higher incidences in cases with than without HCC. MCF, predominant in cirrhotic livers of the high-risk group, were more proliferative, larger and more often involved in formation of NAH than GSF. The results suggest that the FAH are preneoplastic lesions, MCF being more advanced than GSP. We also investigated the relationship of FAH to liver cell dysplasia. Occurrence of SCC, rather than that of LCC, confers FAH an increased proliferation activity and higher risk to nodular transformation, and, hence, should be considered a precancerous condition. Histological detection of FAH and SCC through needle-aspiration liver biopsy can be used for monitoring HCC development in high-risk populations, such as HBV carriers with chronic hepatitis and/or cirrhosis.