Background/Aims: Identification of the risk factors of multicentric hepatocarcinogenesis is important for the clinical management of hepatocellular carcinoma. We investigated hyperplastic foci in non-cancerous liver parenchyma, and clarified their pathological features and clinical significance. Methods: Hyperplastic loci were defined as hypercellular areas, which architecturally and cytologically resembled early hepatocellular carcinoma or adenomatous hyperplasia but did not form macroscopically detectable nodules. Surgically resected livers from 155 patients with hepatocellular carcinoma were examined histopathologica!!y and immunohistochemically. Results: Hyperplastic foci were found in 26 of 155 patients (16.8%). All the patients with hyperplastic foci had chronic liver diseases, and the incidence did not differ between those with chronic hepatitis and those with liver cirrhosis. Six of 92 (6.5%) patients with single primary hepatocellular carcinoma nodules, 8 of 42 (19.0%) with two nodules, and 12 of 21 (57.0%) with more than three nodules had hyperplastic loci. The incidence of hyperplastic foci showed a significant positive correlation with the multiplicity of hepatocellular carcinoma nodules. Immunohistochemically, hyperplastic loci were masses of proliferative hepatocytes similar to adenomatous hyperplasia and early hepatocellular carcinoma. Conclusions: Hyperplastic foci reflect the risk of multicentric hepatocarcinogenesis. Our results suggest strongly that hyperplastic loci are precursors of adenomatous hyperplasia or hepatocellular carcinoma.
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