NONPARENCHYMAL CELL RESPONSES IN PARACETAMOL (ACETAMINOPHEN)-INDUCED LIVER-INJURY

We have analysed Kupffer cell and 'activated' perisinusoidal cell populations in liver biopsies from patients with paracetamol (acetaminophen)-induced hepatic necrosis of varying degrees of severity. Kupffer cells were identified immunohistochemically using the monoclonal antibody KP1 and perisinusoidal cells by identification of alpha-smooth muscle actin expression. Material was available from four groups of individuals: (i) 11 cases with mild (grade I) injury; (ii) six cases with moderate (grade II) injury; (iii) six cases with severe (grade III) injury; and (iv) controls with normal liver histology (n=23). Biopsies in groups (i)-(iii) were obtained within 5 days of drug ingestion. All patients in this study survived and follow-up biopsies were obtained at 4 months, by which time the histological abnormalities had fully resolved. Kupffer cells and perisinusoidal cell numbers were assessed in immunostained preparations of acute and recovery phase biopsies and in control specimens. In acute phase biopsies from patients with grade II and III injury there was expansion of the Kupffer cell and perisinusoidal cell populations within areas of injury. There was a strong correlation between the size of these two cell populations (r=0.886). No significant difference in cell numbers was found between those with grade I injury and controls. In recovery phase biopsies from patients with paracetamol-induced injury, perisinusoidal cell numbers did not differ significantly from normal controls. Kupffer cells numbers also decreased in recovery phase biopsies compared with the acute phase, although there was persistent expansion of the Kupffer cells population in those who originally had grade III injury. These results are consistent with the proposed role for Kupffer cells and perisinusoidal cells in resolution of acute hepatic necrosis and are similar to those observed in experimental models of injury. (C) Journal of Hepatology.