Biochemical and morphological study of the liver injury induced by drugs and chemicals
Journal
Taiwan yi xue hui za zhi. Journal of the Formosan Medical Association
Journal Volume
78
Journal Issue
6
Date Issued
1979-06
Author(s)
Abstract
Biochemical and morphological changes of 10 cases of drug-induced liver injury and 7 cases of chemical-induced liver injury were studied. The offending drugs and chemicals were methandrostenolone, methimazole, chlormezanone, erythromycin estolate, halothane, isoniazid, aspirin, chloroquine, arsenic trioxide and paraquat. Electron microscopic examination was performed on 10 cases. The biochemical changes in cases of drug-induced liver injury could be classified into cholestatic, hepatitic and mixed types. The types of biochemical changes correlated well with the histologic features. For differential diagnosis from viral hepatitis or mechanical biliary obstruction, the biochemical tests alone seemed to have great limitations. A helpful clue to suspect the diagnosis of drug-induced hepatocellular injury was the abnormally higher levels of serum alkaline phosphatase in comparison with the serum bilirubin level. This change was observed in 2 cases of halothane hepatitis and one case of isoniazid hepatitis. If supplemented with clinical history, the usefulness of biochemical tests could be increased. The light microscopic examination on the liver specimens biopsied from cases of drug-induced liver injury showed 4 types of changes; 1) simple cholestasis, induced by methandrostenolone; 2) cholestatic hepatitis, induced by methandrostenolone; 2) cholestatic hepatitis, induced by methimazole, chlormezanone, erythromycin estolate and chloroquine; 3) hepatitis resembling acute viral hepatitis, induced by halothane and isoniazid; 4) hepatitis simulating chronic active hepatitis, induced by chronic ingestion of aspirin. There were no pathognomonic features to differentiate halothane and isoniazid hepatitis from viral hepatitis, although some minor differences were observed. The electron microscopic examination on liver specimens from 2 cases of halothane hepatitis showed prominent injury and increased dividing activities of mitochondria, which were not observed in 2 cases of acute viral hepatitis. One case of isoniazid hepatitis showed marked changes of endoplasmic reticulum without significant alteration of mitochondria. Distinction from viral hepatitis in this case was difficult ultrastructurally. Another case of isoniazid hepatitis had no prominent change of endoplasmic reticulum. The possible value of electron microscopic examination in aiding differential diagnosis of drug induced hepatitis resembling viral hepatitis, especially halothane hepatitis, was emphasized. Chemical-induced toxic liver injury proved diagnostically simple. Arsenic trioxide poisoning simulated pericholangitis in its convalescent stage. Six cases of paraquat poisoning showed histologic changes similar to hypoxic changes of the liver produced in experimental animals under normal blood pressure. Electronmicroscopically, severe alterations of intracytoplasmic organelles and appearance of many intracytoplasmic 'hypoxic vacuoles' were observed.
SDGs
Type
review