[Morphological reaction patterns of the liver induced by drugs]

Drugs are exogenous substances often requiring metabolic transformation to be therapeutically effective. This occurs primarily in the liver, the most important metabolic organ and a structure able to adapt to this burden. Should its adaptive potential be exceeded, damage can occur, affecting principally the liver parenchyma. Such damage manifests itself as disturbed secretory function and as reversible or irreversible structural alteration of the liver cells. The constellation of toxic-degenerative lesions is referred to as hepatosis (toxic hepatosis, toxic hepatopathy). A variety of patterns of damage (lipidosis, necrosis, cholestasis etc.) occur alone or in combination. Depending on the severity and extent of these alterations a secondary inflammatory reaction may result. These changes are manifest as cellular infiltration and proliferation with formation of reticulo-histiocytic nodules or minifocal epitheloid cell reactions and non-caseous epitheloid cell granulomas. The eosinophilic component is striking. In the face of continued toxic exposures, changes resembling those of chronic aggressive hepatitis may develop following the acute changes. Other drug-related liver damage may present as vascular lesions the afferent or efferent venous systems as well as in the sinusoids (i.e. peliosis hepatis, Budd-Chiari syndrome). Moreover there may be neoplastic alterations such as focal nodular hyperplasia or liver cell adenomas. Pathognomonic histologic criteria for drug-induced liver damage have as yet to be recognized, particularly in the case of facultative toxins. Morphologic indications can only suggest that a prior pharmaceutical agent was the likely cause of the damage. Histologic changes must however be viewed in the context of the medical history, clinical and laboratory findings, as well as results of other studies before the conclusion is drawn that the observed liver changes represent drug-induced injury.