EARLY PERIVENULAR FIBROGENESIS - PRECIRRHOTIC LESIONS AMONG MODERATE ALCOHOL CONSUMERS AND CHRONIC-ALCOHOLICS

Cirrhosis is believed to be preceded by ''precirrhotic'' lesions indic ating initial fibrogenesis in the perivenular area. We investigated th ree previously described markers of early perivenular fibrogenesis: th e thickness of the rim of the terminal hepatic venule, perivenular fib rosis and perivenular fibronectin deposition. The frequencies of these features were evaluated and compared to long-term daily alcohol intak e in autopsy series of 120 males comprising abstainers, moderate alcoh ol consumers and chronic heavy alcohol consumers. Thickening of the ri m of the terminal hepatic venule showed no correlation to the long-ter m daily ethanol intake. In contrast, compared to abstainers, daily alc ohol intake between 40 and 80 g for an average of 25 years was associa ted 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 a ssociated 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 n ot, however, further increase the occurrence of these lesions. A daily intake below 40 g of absolute alcohol was not associated with signs o f early perivenular fibrogenesis. In this study, the frequencies of su bjects with perivenular fibrosis and perivenular fibronectin depositio n correlated with the amount of daily alcohol intake. A daily intake b etween 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 be tween 40 and 80 g represents a ''threshold'' level, beyond which the r isk of alcoholic liver fibrosis increases significantly. The majority (50-70%) of chronic heavy alcohol consumers presented signs of early p erivenular fibrogenesis, whereas cirrhosis was found in only 20% of he avy consumers. This could suggest that alcohol-induced fibrotic lesion s of the liver may develop in the majority of people, but factors othe r than cumulative alcohol consumpation may have a critical impact on t he progression of early liver fibrosis to cirrhosis. (C) Journal of He patology.