Hepatic fibrosis caused by alcohol.

The past decade of research has brought us closer to an understanding of the mechanisms whereby alcohol promotes fibrosis in liver. The perivenular and perisinusoidal fibrosis that characterizes alcoholic cirrhosis suggests that it is a unique entity, distinct from other types of fibrotic liver disease. On a cellular level, though, the target population and the regulatory events that control fibrogenesis may be typical of all types of fibrotic liver disease. The putative pathways to alcoholic fibrosis are exemplified in Figure 1. Fibrosis can be either the direct result of a stimulus from ethanol or one of its metabolites to a target cell population, presumably the lipocytes, or it can begin indirectly in response to hepatic inflammation. The indirect pathway to hepatic fibrosis is likely to be initiated by cytokines, elaborated by inflammatory cells. In addition, invasion of the liver by inflammatory cells may disrupt the normal hepatic extracellular matrix, which may in itself act as a stimulus for fibrogenesis by altering critical cell-matrix interactions. If alteration of the normal hepatic matrix is sufficient to promote fibrogenesis, it may act as a fixed stimulus that perpetuates fibrogenesis in the absence of ongoing inflammation. This may explain the progression of alcoholic fibrosis in some patients in the apparent absence of alcoholic hepatitis. It has been gratifying to observe a consensus emerge among experimental observations regarding the process of alcoholic fibrosis. In particular, the discovery of transitional cells in fibrotic liver tissue, and their relationship to lipocytes, correlates well with studies documenting activation of lipocytes in culture to a fibrogenic phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)