To characterize cellular responses during hepatic regeneration, we examined 13 explant livers and 5 liver allografts by immunohistochemistry for cytokeratin 7, HepPar1, CD68, alpha-smooth muscle actin (alpha-SMA) and proliferating cell nuclear antigen as well as reticulin and Masson-trichrome staining. Within a week after liver damage, elongated CD68-positive cells were detected along the border of necrotic area. The number of alpha-SMA-positive 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 increased in number within lobules and portal tracts. Ductular proliferation occurred 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 hepatocytes and irregular fibrosis were diffusely present. Other nonparenchymal cells were not significantly changed. These observations indicate that chronological interaction between nonparenchymal and parenchymal cells occur during the course of human hepatic regeneration and suggest extensive porto-periportal fibrosis more than a few months after the onset of fulminant hepatitis is a major indicator of chronic functional impairment necessitating liver transplantation.
Actins/analysis ; Antigens, CD/analysis ; Antigens, Differentiation, Myelomonocytic/analysis ; Human ; Immunohistochemistry ; Keratin/analysis ; Liver/*cytology ; *Liver Regeneration ; Proliferating Cell Nuclear Antigen/analysis

Hepatocellular adenoma (HCA) is an uncommon benign hepatic tumor, and the use of oral contraceptives is known to contribute to the development of HCA. Recently, a genotype and phenotype classification system for HCA was suggested, and malignant transformation to hepatocellular carcinoma (HCC) was shown to be strongly associated with activating mutations in beta-catenin. Here, we report three cases of HCA in Korean patients: 7-cm, inflammatory and beta-catenin-activated HCA with HCC transformation in a 46-year-old man; 13-cm, beta-catenin-activated HCA with cytological atypia in a 23-year-old woman; and 10-cm, pigmented, inflammatory and beta-catenin-activated HCA in a 36-year-old man. All cases exhibited the nuclear expression of beta-catenin and diffuse cytoplasmic expression of glutamine synthetase upon immunohistochemical staining. All tumors were completely resected, and the patients were followed for 3 to 6 years with no evidence of local recurrence or metastasis.
Adult ; Carcinoma, Hepatocellular/*metabolism ; Female ; Humans ; Liver Neoplasms/*metabolism ; Male ; Middle Aged ; Republic of Korea ; Young Adult ; beta Catenin/*metabolism