title: Early perivenular fibrogenesis--precirrhotic lesions among moderate alcohol consumers and chronic alcoholics.
abstract: Cirrhosis is believed to be preceded by "precirrhotic" lesions indicating initial fibrogenesis in the perivenular area. We investigated three previously described markers of early perivenular fibrogenesis: the thickness of the rim of the terminal hepatic venule, perivenular fibrosis and perivenular fibronectin deposition. The frequencies of these features were evaluated and compared to long-term daily alcohol intake in autopsy series of 120 males comprising abstainers, moderate alcohol consumers and chronic heavy alcohol consumers. Thickening of the rim of the terminal hepatic venule showed no correlation to the long-term daily ethanol intake. In contrast, compared to abstainers, daily alcohol intake between 40 and 80 g for an average of 25 years was associated in an increased number of subjects with perivenular fibrosis (13.3% vs 38.9%, p < 0.05), and with perivenular fibronectin deposition (13.3% vs 44.4%, p < 0.025). Similarly, daily intake exceeding 80 g was associated in an increased number of subjects with perivenular fibrosis (56.1%, p < 0.001) and with perivenular fibronectin deposition (56.1%, p < 0.001). A daily intake exceeding 80 g (110 g/d vs 240 g/d) did not, however, further increase the occurrence of these lesions. A daily intake below 40 g of absolute alcohol was not associated with signs of early perivenular fibrogenesis. In this study, the frequencies of subjects with perivenular fibrosis and perivenular fibronectin deposition correlated with the amount of daily alcohol intake. A daily intake between 40 and 80 g was associated with approximately a three-fold and a daily intake exceeding 80 g with approximately a five-fold increase in the risk of these features. This could suggest that daily intake between 40 and 80 g represents a "threshold" level, beyond which the risk of alcoholic liver fibrosis increases significantly. The majority (50-70%) of chronic heavy alcohol consumers presented signs of early perivenular fibrogenesis, whereas cirrhosis was found in only 20% of heavy consumers. This could suggest that alcohol-induced fibrotic lesions of the liver may develop in the majority of people, but factors other than cumulative alcohol consumpation may have a critical impact on the progression of early liver fibrosis to cirrhosis.
authors.affiliation: Department of Forensic Medicine, University of Helsinki, Finland.
authors.forename: V
authors.initials: V
authors.lastname: Savolainen
authors.forename: M
authors.initials: M
authors.lastname: Perola
authors.forename: K
authors.initials: K
authors.lastname: Lalu
authors.forename: A
authors.initials: A
authors.lastname: Penttilä
authors.forename: I
authors.initials: I
authors.lastname: Virtanen
authors.forename: P J
authors.initials: PJ
authors.lastname: Karhunen
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000378:metabolism / Q000473:pathology*; D000437:Alcoholism / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D005353:Fibronectins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014699:Venules / Q000737:chemistry / Q000473:pathology
chemical_list: D005353:Fibronectins