Activation of Latent Infection by Indomethacin: a Report of Three Cases

ComncainBRITISH96 hepatocellular damage was seen in all six cases biopsied, but cholestasis was seen in only two of them.In this respect our findings are in conformity with the biochemical observations of Eisalo and of Palva and Mustala, in that abnormal enzyme levels are seen more frequently than abnormal biliary excretion tests.According to Eisalo et al. the biochemical changes of liver damage at contraceptive dose levels are transient, lasting only one to four weeks.The transaminase levels return to normal even when administration of the drug is continued.The recog- nition of these changes therefore requires repeated determina- tions in the first few weeks of drug administration-and this may be the reason for its failure to be recognized in some of the series mentioned at the beginning of this paper.However, at the higher dosage given in our series the raised transaminase levels continued throughout treatment.The presence of an alkylated group in the C17 position is the steroid configuration which is apt to induce hepatic damage and cholestasis when the drug is given in sufficient dosage for pro- longed periods (Sherlock, 1963).Both the progestogen and the oestrogen components of Lyndiol possess this configuration, and in our restricted series the combination of the two hormones caused considerably more liver damage than either alone.This is in conformity with Eisalo's findings.It has been suggested that there is synergic toxicity of the two components (Borglin, 1965).This is not proved, and the greater damage observed when they are combined may be purely an additive effect.At contraceptive dose levels Eisalo found a rise in transaminase levels from the progestogen component alone in only one out of 25 cases.At our dose level we found such changes in three out of seven cases, associated with parenchymal cell necrosis.Hepatotoxic changes following the administration of progestogens are probably therefore dose dependent.From Eisalo's reports (1964, 1965), it might be deduced also that for the same dose the hepatotoxic effect is greater in the post-menopausal than the pre-menopausal patient. SUMMARYA correlation has been established between raised serum glutamic oxalacetic transaminase levels and histological evidence of hepatocellular damage in a series of four postmenopausal patients treated by Lyndiol and seven patients treated by lynoestrenol, its progestogen component.Histological evidence of hepatocanalicular damage in a proportion of cases has also been demonstrated, but this does not appear to run parallel to changes in the transaminase levels.Raised enzyme levels persisted for many months when drug dosage at high levels was maintained.Mestranol, which is the oestrogen component of Lyndiol, caused no abnormality in biochemical liver tests in the four patients studied.The results suggest that the hepatotoxic effects of oral con- traceptives are mainly due to their progestogen content.