Ultrastructure of initial stages of perivenular fibrosis in alcohol-fed baboons.

Perivenular fibrosis was studied in baboons pair-fed with alcohol containing or isocaloric control diets for up to 8.5 years, and biopsies were performed on the animals one to two times a year. The number and types of mesenchymal cells surrounding the terminal hepatic venules were examined at various stages of thickening of the rim of the terminal hepatic venules by light and electron microscopy. The number of mesenchymal cells increased with progression of fibrosis and showed good correlation with the thickness of the rim (r = 0.7435, P less than 0.001, n = 56). myofibroblasts were the most common mesenchymal cells. They were present around the terminal hepatic venules in the control animals and proliferated after alcohol. This was associated with increased deposition of collagen fibers around the terminal hepatic venules. This fibrotic process extended into the perisinusoidal space of the centrolobular areas, sometimes connecting with pericellular fibrosis and/or fat granuloma, which developed in the lobule. Thus, in baboons fed alcohol, perivenular fibrosis is associated with myofibroblast proliferation followed by collagen deposition. Myofibroblast proliferation appears to represent the earliest detectable precursor lesion leading to hepatic fibrosis in alcoholic liver injury.