In Vitro Tests

The difficulties encountered in the diagnosis of drug-induced liver injury have led to attempts to develop in vitro diagnostic tests. Assays have been devised to study the cytotoxic effect of metabolites generated by a hepatic microsomal drug-metabolising system on the peripheral blood mononuclear cells from patients suffering hepatotoxicity due to phenytoin and sulphonamides (Rieder et al., 1989; Gennis et al., 1991). The lymphocyte transformation test aims to demonstrate in vitro proliferation of a patient's lymphocytes in response to the drug in question. Considering the complexity of the immunological events necessary for the in vivo induction of specifically sensitised T-cells, it is not surprising that the test is positive only in 30% of all patients with suspected drug-induced liver injuries (Berg and Becker, 1995). The use of sera collected from healthy volunteers after drug intake (containing ex vivo drug antigens) and the addition of prostaglandin inhibitors to the cultures (to prevent inhibition of lymphocyte response by prostaglan-din-producing suppresser cells) can increase the sensitivity of the test up to 56% (Maria and Victorino, 1998). However, the fact that these in vitro tests are extremely tedious and operator-dependent has limited their widespread use.

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