THE MALLORY BODY - MORPHOLOGICAL, CLINICAL AND EXPERIMENTAL STUDIES -LITERATURE SURVEY .1.

To aid understanding of markers of disease and predictors of outcome i n alcohol-exposed systems, we undertook a literature survey of more th an 700 articles to view tbe morphological characteristics and the clin ical and experimental epidemiology of the Mallory body. Mallory bodies are filaments of intermediate diameter that contain intermediate fila ment components (e.g., cytokeratins) observable by conventional light microscopy or immunohistochemical methods, identical in structure rega rdless of initiating factors or putative pathogenesis. Although three morphological types can be identified under electron microscopy (with fibrillar structure parallel, random or absent), they remain stereotyp ical manifestations of hepatocyte injury. A summary of the conditions associated with Mallory bodies in the literature and their validity an d potential etiological relationships is presented and discussed, incl uding estimates on the combined light microscopic and immunohistochemi cal prevalences and kinetics. Emphasis is placed on proper confounder control (in particular, alcohol history), which is highly essential bu t often inadequate. These conditions include (mean prevalence of Mallo ry bodies in parentheses): Indian childhood cirrhosis (73%), alcoholic hepatitis (65%), alcoholic cirrhosis (51%), Wilson's disease (25%), p rimary biliary cirrhosis (24%), nonalcoholic cirrhosis (24%), hepatoce llular carcinoma (23%), morbid obesity (8%) and intestinal bypass surg ery (6%). Studies in alcoholic hepatitis strongly suggest a hit-and-ru n effect of alcohol, whereas other chronic liver diseases show evidenc e of gradual increase in prevalence of Mallory bodies with severity of hepatic pathology. Mallory bodies in cirrhosis do not imply alcoholic pathogenesis. Obesity, however, is associated with alcoholism and dia betes, and Mallory bodies are only present in diabetic patients if alc oholism or obesity complicates the condition. In addition, case studie s on diseases in which Mallory bodies have been identified, along with pharmacological side effects and experimental induction of Mallory bo dies by various antimitotic and oncogenic chemicals, are presented. Ma llory bodies occur only sporadically in abetalipoproteinemia, von Gier ke's disease and focal nodular hyperplasia and during hepatitis due to calcium antagonists or perhexiline maleate. Other conditions and clin ical drug side effects are still putative. Finally, a variety of exper imental drugs have been developed that cause Mallory body formation, b ut markedly different cell dynamics and metabolic pathways may raise q uestions about the relevance of such animal models for human Mallory b ody formation. In conclusion, the Mallory body is indicative but not p athognomonic of alcohol involvement. A discussion on theories of devel opment and pathological significance transcending the clinical framewo rks will be presented in a future paper.