Parenchymal and Nonparenchymal Cellular Responses in Human Hepatic Regeneration

Abstract

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.

Cross‐species immunohistochemical investigation of the activation of the liver progenitor cell niche in different types of liver disease

“…This relation has, however, not substantially been shown in dogs. Moreover, studies focusing on the relationship between the LPC and the HSC/MF are scarce, as are studies investigating diseases with different histopathological conditions (12,16,45,63,67,68). Finally, the subtype of HSC/MF involved in different types of disease has not been specified.…”

Distribution of hepatic stem cell markers in human liver with massive hepatic necrosis

“…Since most patients with fulminant hepatic failure have fatal clinical courses, liver transplantation became the ultimate therapeutic modality for MHN. Thus, the explanted liver of MHN has been used to observe sequential histopathological characteristics of hepatic regeneration 22 as well as to detect the presence of hepatic stem cells 23…”

“…21 Since most patients with fulminant hepatic failure have fatal clinical courses, liver transplantation became the ultimate therapeutic modality for MHN. Thus, the explanted liver of MHN has been used to observe sequential histopathological characteristics of hepatic regeneration 22 as well as to detect the presence of hepatic stem cells. 23 In the present study, we observed that potential hepatic stem cells expressing c-kit and CD133 appear primarily along the portoparenchymal interface and rarely in the parenchyma at the early stage of hepatic regeneration, and that their numbers increase during the regeneration process.…”