Hepatic fibrosis caused by alcohol. 1990

J J Maher
Liver Center Laboratory, San Francisco General Hospital, CA 94110.

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)

UI MeSH Term Description Entries
D008104 Liver Cirrhosis, Alcoholic FIBROSIS of the hepatic parenchyma due to chronic excess ALCOHOL DRINKING. Alcoholic Cirrhosis,Hepatic Cirrhosis, Alcoholic,Alcoholic Hepatic Cirrhosis,Alcoholic Liver Cirrhosis
D010215 Papio A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of five named species: PAPIO URSINUS (chacma baboon), PAPIO CYNOCEPHALUS (yellow baboon), PAPIO PAPIO (western baboon), PAPIO ANUBIS (or olive baboon), and PAPIO HAMADRYAS (hamadryas baboon). Members of the Papio genus inhabit open woodland, savannahs, grassland, and rocky hill country. Some authors consider MANDRILLUS a subgenus of Papio. Baboons,Baboons, Savanna,Savanna Baboons,Baboon,Baboon, Savanna,Papios,Savanna Baboon
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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