THE MALLORY BODY - THEORIES ON DEVELOPMENT AND PATHOLOGICAL SIGNIFICANCE .2.

Drawing on data from a previously published literature survey on the c linical and experimental epidemiology of the Mallory body, we discuss current theories on its development in apro et contra manner. Conclusi ons have been largely left open to the interpretations of the reader b ecause many are still speculative. The main results of this study char acterize Mallory bodies as stereotypical histological byproducts to di verse hepatic injuries (mostly alcohol associated) of questionable pat hogenic importance. The temporal characteristics of Mallory bodies cas t doubt on their role in hepatic neoplasia both as a disease marker an d a causative agent, and prognosis studies suggest that they may be co nsidered preterminal markers in some nonalcoholic liver diseases but r emain prognostically unimportant in most studies on alcoholic patients . By similar line of inquiry, no consistent relationships may be found with disease severity or duration in alcoholic liver diseases. The ro les of vitamin A deficiency and protein-calorie malnutrition are circu mstantial. Drugs known to have calcium-antagonist properties and the p hysiological characteristics of the stress-response protein ubiquitin support the concept of defective protein systems in Mallory body patho genesis. Disproportionate hepatic copper accumulation seems both epide miologically and topographically associated with Mallory bodies, but t hese connections are largely unsupported by exposure studies. Many arg uments still downplay the importance of uncoordinated changes in hepat ic oxygen delivery and consumption, but ischemia-reperfusion studies s uggest a role of oxygen-derived free radicals in the liver injuries un der scrutiny. Finally, the role of Mallory bodies in the control syste m of hepatocyte function is addressed, and indirect evidence lends cre dence to a cybernetic approach in future study designs. It is reasonab le to assume that different elements of a multifactorial setting opera te with varying intensity over time as this may account for some of th e controversies that exist. In conclusion, the biological significance of Mallory bodies is still mystery. It is not known whether Mallory b odies represent an epiphenomenon or play a role themselves in the init iation and continuation of liver damage.