Perspectives in the pathogenesis of halothane-induced hepatitis

The evolution of today's accepted theories regarding the pathogenesis of halothane-induced hepatitis (HIH) is traced from a selection of the extensive literature covering this rare condition. Initial postulates indicted an immunological mechanism. The development of a laboratory model (starved, phenobarbitone-pretreated, hypoxic rat) uncovered two other 'triggers': highly reactive (toxic) free-radical intermediates generated from a reductive metabolic pathway; and hypoxic stress alone. None of these proposed mechanisms incontrovertibly excludes the other and complex interrelationships may exist. Continuing research utilizing sophisticated analytical tools and new HIH animal models suggests that the field remains incompletely explored.