Histogenesis of alcoholic fibrosis and cirrhosis in the baboon

Abstract

Sequential liver specimens of 18 baboons exposed for up to 6 years to alcohol on a nutritionally adequate diet, as well as those of pair-fed controls, were examined by light microscopy. Whereas control animals failed to develop pathologic changes, in all baboons exposed, ethanol produced initial steatosis and subsequently fibrosis. Emphasis was on the pattern of the fiber accumulations as related to lesions of the hepatocytes. Segmented neutrophilic leukocytes were rarely observed, and the picture of frank alcoholic hepatitis was absent, but diffusely increased mononuclear sinusoidal cells and interstitial clusters of such cells with PAS-positive macrophages were abundant. Fibrosis proceeding to septum formation was associated mainly with large-droplet steatosis. Septum formation was initiated by excess layers of reticulin around steatotic hepatocytes or, more frequently, by linking of fiber accumulations around the clusters of mononuclear cells, in both instances with subsequent deposition of collagen fibers. Both processes were prominent in the centrolobular zone, creating a perivenous net-like fibrosis, but septum formation also started within the lobular parenchyma and eventually linked with the barely altered portal tracts. Fifteen alcohol-fed baboons developed septums, with diffuse septal fibrosis in 5; 4 proceeded to septal cirrhosis and 1 each to micronodular and to mixed micromacronodular cirrhosis. Cirrhosis in the baboons thus develops without the conspicuous polymorphonuclear inflammation characteristic of human alcoholic hepatitis. These observations indicate a pathway to cirrhosis over creeping fibrosis that might play a role also in man, instead of (or supplementing) the one proceeding over alcoholic hepatitis.