Peripheral lymphocyte culture in diagnosis of drug-induced liver injury

Abstract

In order to evaluate the usefulness of the peripheral lymphocyte culture method for the diagnosis of drug-induced liver injury, the present study was carried out on 21 cases of druginduced liver injury diagnosed on the basis of histologic, clinical and laboratory data (Group A) and 8 cases with liver cirrhosis of unknown etiology (Group B) as well as 17 healthy controls with normal liver function (Group C). The lymphocytes obtained from peripheral blood of the patients were cultured according to the method of Hirschhorn et al., in presence of serial concentrations of appropriate candidate drugs as a stimulant. Incorporation of C¹⁴-thymidine into lymphocytic DNA was measured as an index of lymphocyte stimulation by the method of Shtacher et al., and the uptakes over 75cpm by the total lymphocytes were judged as positive.
Nine cases in Group A, 2 in Group B and 1 in Group C showed a positive lymphocytes stimu lation. The drugs which showed the positive stimulation were tetracycline, chlotaon, sigmamycin, ethionamide, PAS, sulpyrin, and ajmaline. Out of 9 cases which showed positive stimulation, six cases were cholestatic type of liver injury, and the remaining three were of hepatitic type. The lymphocyte stimulation was positive in all of 6 cases which showed over 50 units of icterus index and in all of 4 cases which showed over 15 units (Bessey-Lowrey) of serum alkaline phosphatase activity during the course of the disease.
The results suggest that peripheral lymphocyte culture method is a useful method for diagnosis of drug-induced liver injury.