Liver cell necrosis in chlorpromazine jaundice (allergic cholangiolitis): A serial study of twenty-six needle biopsy specimens in nine patients

Abstract

Nine patients with chlorpromazine jaundice were studied for periods varying from forty-three days (Case 8) to over three years (Case 1). Twenty-six needle biopsy specimens of the liver were obtained in these nine patients, varying from one (Case 7) to five (Case 9) biopsy specimens per patient. The clinical, laboratory and histopathologic features are described in detail in case protocols. Although much less prominent than in viral hepatitis, necrosis of liver cells is found in chlorpromazine jaundice, notably in the centrolobular zones adjacent to the evidences of cholestasis, and frequently also in periportal intralobular extensions of the portal exudate. It is accompanied and followed by intralobular liver cell regeneration, characterized both by multinucleation and by mitosis. The necrosis of liver cells is reflected in rises in serum glutamic-pyruvic transaminase, and to lesser degree in serum glutamic-oxaloacetic transaminase. The findings suggest that necrosis of liver cells (hepatitis) may play a more important role in the causation of chlorpromazine jaundice than is generally recognized. The disease histopathologically is of prolonged duration compared with the transitory symptomatology. This duration is reflected in the laboratory measurements, particularly in the serum alkaline phosphatase, and often in persisting eosinophilia. There was no evidence in these cases of the development of permanent residual damage or fibrosis in the liver, although a transient portal fibrosis was observed to follow resolution of the portal infiltrations. Disorganization and necrosis of interlobular bile ducts, followed by their regeneration, occurred in the two most severe cases of this series, suggesting extension of a destructive process ordinarily limited to the intralobular cholangioles.