Drug-induced liver injury and microsomal arylamidase activity in needle biopsy of human liver.

The relation between the activities of arylamidase (one of the non-specific carboxylesterases) located exclusively in smooth endoplasmic reticulum (SER), and microscopical changes of the hepatocytes, was studied in three patients treated with phenobarbital and twenty-five patients injured by various other drugs. A micro-method was used for the determination of the enzyme activity in small pieces of liver (5-15 mg) obtained by needle biopsy. The arylamidase activity in seven normal livers was 0.43 +/- 0.05 (SD) nmol benzylhydrazine/micron protein/hr formed from isocarboxazid. The mean value in the livers treated with phenobarbital was statistically different from the value before phenobarbital treatment (P less than 0.05). Of sixteen cytotoxic type samples, seven showed low activity and eight high activity, respectively. Of the seven mixed-type samples, three showed mildly low activity and four normal activity. The frequency of the cytotoxic type is statistically different from that of the cholestatic (mixed and pure cholestatic) type comparing the abnormal activity with normal activity (P less than 0.05). The degree of enzyme activity was related to changes such as pyknosis, enlarged nuclei and centrilobular zonal necrosis. The ultrastructure of the material taken from three patients after phenobarbital treatment and one patient with ibuprofen-induced injury showed prominent increase and vesiculation of SER respectively. The study shows that drug-induced liver injury is closely related to the activity of SER, and that the changes in hepatocytes in cytotoxic type may result from the functional abnormality of SER.