Diagnostic value of specific T cell reactivity to drugs in 95 cases of drug induced liver injury

摘要

Background—Diagnosis of drug induced liver injuryis usually based on a temporal relation between drug intake andclinical picture as well as on the exclusion of alternative causes.More precise diagnosis has been attempted by using in vitro specific Tcell reactivity to drugs but the test has never reached general acceptability because of frequent negative results which could beexplained, in part, by prostaglandin producing suppressor cells (PPSC).
Aim—To analyse the diagnostic value of a modifiedtest where lymphocyte responses to drugs are detected in the presenceof a prostaglandin inhibitor. 
Patients—Ninety five patients with a clinicaldiagnosis of drug induced liver injury, 106 healthy controls, 35 individuals with recent exposure to the same drugs without adverseeffects, and 15 patients with liver disease unrelated to drugs. 
Methods—Peripheral blood mononuclear cells (PBMC)were cultured in the presence of drugs alone and in the presence ofdrugs and a prostaglandin inhibitor. Responses were assessed by3H-thymidine incorporation in lymphocytes. Results wereexpressed as counts per minute and as stimulation indexes (SI). 
Results—When PBMC were stimulated with drugsalone, lymphocyte sensitisation to drugs (SI>2) was detected in 26%of the cases. This was noticeably increased (56%) when a prostaglandininhibitor was added to the cultures. No reactivity was found incontrols. In patients with possible sensitivity to several drugs,lymphocyte reactivity was detected to only one drug. The severity ofthe lesions, as assessed by aminotransferase concentrations and disease duration, was lower in patients with evidence of PPSC. 
Conclusions—This new approach is useful for thediagnosis of drug induced liver injury, particularly in patientsexposed to more than one drug; furthermore, the presence of putativePPSC is associated with less severe forms of drug induced hepatitis.