The development of ductular structures in acute hepatitis with panacin
ar necrosis was studied in 15 cases of fulminant hepatitis with variab
le clinical duration, using immunohistochemical markers. The immunophe
notype of ductular structures was assessed by the expression of two bi
le duct epithelium determinants, wide spectrum cytokeratin and epithel
ial membrane antigen (EMA), and by their glycoconjugate expression usi
ng the specific binding lectins Dolichos biflorus agglutinin (DBA) and
soybean agglutinin (SEA). Ductular structures showed a predilective,
but not a strictly selective location in acinar zone 1 and at the peri
phery of newly formed parenchymal nodules. All were positive for kerat
in, while EMA and the lectins were identified less frequently. Cytoker
atin expression was additionally observed in hepatic cells with no oth
er phenotypic alteration: this occurred along isolated hepatic cords,
within parenchymal remnants, in the spared parenchyma in acinar zone 1
and occasionally at the periphery of parenchymal nodules. The presenc
e of cytokeratin expression in liver cell plates in association with i
ntermediate morphological stages of tubular remodelling speaks in favo
ur of biliary metaplasia of hepatocytes. This process may represent a
phenotypic-functional accommodation of hepatocytes to an altered micro
environment, due to loss of parenchymal integrity. During the phenotyp
ic shift, altered cytokeratin expression appears as one of the earlies
t biliary features, while EMA and the expression of glycoconjugates re
present maturation markers.