Abstract
Publisher Summary This chapter focuses on drugs leading to hepatic diseases and for which metabolism plays an important role. The clinical characteristics and the hypothesis put forward to explain the triggering of the hepatitis are provided. The two main drugs used as examples are tienilic acid and dihydralazine. Some xenobiotics, including drugs, are toxic through an autoimmune mechanism. The main targets are the blood cells, skin, kidney, and liver. Hepatitis caused by this type of drug presents very characteristic features, which are (1) a delay between the beginning of the treatment and the onset of symptoms, (2) no obvious dose-toxicity relationship, (3) fever, rash, and eosinophilia often accompanying the hepatitis, and (4) presence of autoantibodies that are the hallmark of the disease. Heterologous systems were quite useful in proving some of the hypotheses, identification of the target of the autoantibodies and the epitopes, identification of the enzyme responsible for the production of the reactive metabolite, and identification of the target of the reactive metabolite(s).
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