A clinical and histochemical study of cholestasis.

A histochemical study of conjugated and total bilirubin was made on liver biopsies of 150 patients. Three types of cholestasis were defined: type I, characterized by the presence of intracellular pigment granules in the hepatocytes; type II, showing intracellular granules and extracellular thrombi (this group may be subdivided according to the eventual presence of coarse pigment deposits in the parenchymal cells); and type III, showing intracellular granules, extracellular thrombi, and also bile pigment in the Kupffer cells. The fine liver cell granules correspond mainly to conjugated bilirubin, whereas the coarse deposits usually contain unconjugated pigment. The extracellular thrombi mostly contain conjugated bilirubin; the Kupffer cell pigment is predominantly of the unconjugated type. In cholestasis types II and III a diffuse directly reacting pigment is also observed. The finding of unconjugated pigment in different locations and the eventual deconjugation by beta-glucuronidase is discussed. A correlation was found between the different types of cholestasis, the level of bilirubinaemia, and its dynamic evolution. This suggests that the proposed types of cholestasis may represent successive stages of increasing cholestasis. The type of cholestasis and the nature of the pigment are largely independent of the aetiology. It is shown that a large percentage of minor degrees of cholestasis is missed when only conventional histological methods are used. The mechanisms by which morphological cholestasis is brought about are discussed in the light of the present findings.