Immunolocalization of regenerating cells after submassive liver necrosis using PCNA staining

Little data exist on the proliferative state of liver cells and its relationship with various morphological findings in acute liver failure (ALF) in man. In this study we used the monoclonal antibody NCL-PCNA (clone PC-10) against the proliferating cell nuclear antigen (PCNA) to detect cycling cells in paraffin sections of 3 normal livers, 14 post-mortem needle-specimens of submassive hepatic necrosis (SHN) due to paracetamol overdosage (POD), and 10 hepatectomy specimens obtained at transplantation in patients with acute or subacute liver failure of presumed viral aetiology. In normal livers, only occasional sinusoid-lining cells were stained, whereas in SHN following POD or presumed viral hepatitis, hepatocytes of variable morphology showed significant immunoreactivity. Following POD, immunoreactivity was higher in samples taken within 5-6 days than in those obtained at 9-11 days, a pattern reminiscent of the decrease in the rate of regeneration, previously documented after partial hepatectomy in humans. Immunolabelled hepatocytes were aggregated in multiacinar 'nodules' in cases with a map-like distribution of collapsed and non-collapsed parenchyma. Ductules demonstrated comparatively less staining, but extensive labelling was exceptionally found in areas of complete hepatocellular dropout. In these areas, small elongated cells with strongly PCNA-positive ovoid nuclei, forming periportal sprouting cords or incorporated into the lining of ductules, were most remarkable in that they closely resembled 'oval cells' described in animal studies.