Role of Alcohol in the Pathogenesis of Cirrhosis *

For over a century clinicians and pathologists have debated the role of alcohol in the pathogenesis of cirrhosis. Only in the last decade, however, has general agreement been reached on certain principles underlying the complex inter-relationships between alcohol ingestion, food intake, and alterations in the structure of the liver. Unfortunately, this has led to the erroneous impression in some quarters that the problem has been solved, and that further investigation is no longer needed. It is the purpose of this discussion, therefore, to review very briefly the evidence on which our current concept of the r6le of alcohol in the pathogenesis of cirrhosis is based and to call attention to some gaps in our knowledge. In tracing the evolution of this concept it is possible to discern three distinct, but broadly overlapping, periods dominated in turn by the morphologist, the toxicologist, and the nutritionist. What I choose to call the morphologist's era may be said to have begun with Laennec's description' of the anatomical lesion in cirrhosis in 1826. It was a period marked by a bitter controversy between the proponents of the view that alcohol was the direct cause of cirrhosis and those who denied any relationship between the two. In the end, however, both sides were forced into the intermediate position so well summarized by Jolliffe and Jellinek2 in 1941: