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Editor,—I read with interest Maria and Victorino’s work (Gut 1997;41:534–40) on the diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury. They are to be congratulated on assembling the largest group of patients with suspected drug induced hepatotoxicity and attempting to assess causality using their lymphocyte test.
In their discussion, when referring to the clinical significance of the presence of prostaglandin producing suppressor cells in vitro, they state that, “patients in which this phenomenon was detected had a less severe disease, as assessed by aminotransferase concentrations and more rapid cure.” There is another potential clinical significance to the interpretation of their in vitro results and that is that non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of developing drug induced hepatotoxicity in this unpredictable, hypersensitivity type of liver injury. Gutthann and Rodriguez1 showed that patients taking an NSAID plus one other drug known to cause sporadic liver injury were at almost twice the risk of being admitted to hospital with biochemical and clinical evidence of liver disease than those taking a potentially hepatotoxic drug alone (table 1).
It would be interesting to know in Maria and Victorino’s group of patients how many were taking an NSAID in addition to the suspected hepatotoxin and whether this was higher than in their control groups or a standard adult population.
Given the large number of patients that consume NSAIDs, even a small increase in the risk of potentiating hypersensitivity reactions to other drugs, including organs other than the liver, could represent a major health issue.
References
Risk of admission to hospital with drug induced liver injury in those taking NSAIDs plus one other drug known to cause sporadic liver injury
Consumption of NSAIDs by patients with drug induced hepatitis and two control populations
Reply
Editor,—We showed that the in vitro phenomenon of putative prostaglandin producing suppressor cells demonstrated in patients with drug induced hepatitis was significantly associated with a less severe form of disease and a more rapid cure. It is possible to speculate that this in vitro phenomenon could also occur in vivo and play a part in the down regulation of the immune response triggered by the drug or its metabolites.
We think that Dr Bartle’s point suggesting that there is another potential clinical significance to the interpretation of our in vitro results, namely that non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of developing drug induced hepatotoxicity, is a very interesting possibility. Our own epidemiological data are consistent with the results of the epidemiological study presented by him, showing that patients taking NSAIDs have an increased risk of developing liver injury induced by other drugs. In fact, we compared the frequency of NSAID consumption in our population with drug induced liver injury with two different adult populations integrated into prospective studies, one consisting of patients admitted to our internal medicine unit in the University Hospital and the other consisting of patients followed in the primary care setting (table 1). Patients with drug induced hepatitis took significantly more NSAIDs than the control populations (χ2 test, p<0.0001).
Although all epidemiological evidence suggests that NSAIDs increase the risk of hepatotoxicity from other drugs, the possibility that this could have an immunological basis has to be viewed with caution. In fact, it has been shown that prostaglandin E2has a protective effect in cases of hepatitis induced by hepatotoxic agents and cytopathic viruses, both in animal models and in humans,1-1-1-3 suggesting that a non-immunological mechanism may also be involved in this association.