Perivenular Fibrosis in Alcoholic Liver Injury: Ultrastructure and Histologic Progression

Nakano, Masayuki; Worner, Theresa M.; Lieber, Charles S.

doi:10.1016/s0016-5085(82)80006-1

Cited by 232 publications

(63 citation statements)

References 23 publications

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“…While many authors try to rephrase the zonal pathology of fibrosis as, e.g., a ''scarring of zone 3'' (see Nakano 43 ), we found in many reports that fibrous deposition occurs in a manner compatible with the C-M-C connection, i.e., starting in the centrilobular zones and extending to the midseptal region. Strictly speaking, these findings are unably explained under the acinar context; the C-C fibrosis crossing the midpoint of a portal-portal connecting line is commonly seen in the pig serum-induced fibrosis, 30,32 the CCl 4 -induced liver injury, 20,44 and the alcoholic liver disease.…”

Section: Vitamin a And Hepatic Fibrosismentioning

confidence: 67%

“…Strictly speaking, these findings are unably explained under the acinar context; the C-C fibrosis crossing the midpoint of a portal-portal connecting line is commonly seen in the pig serum-induced fibrosis, 30,32 the CCl 4 -induced liver injury, 20,44 and the alcoholic liver disease. 43 The MCI (Fig. 3B) shows that the stellate cells with low vitamin A values were located anywhere in the lobule.…”

Section: Vitamin a And Hepatic Fibrosismentioning

confidence: 97%

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Zonal and regional differences identified from precision mapping of vitamin a-storing lipid droplets of the hepatic stellate cells in pig liver: A novel concept of addressing the intralobular area of heterogeneity

1998

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Knowledge of hepatic heterogeneity has been strikingly increased, while an accurate means for addressing intralobular positions is still lacking. We examined pig liver preparations of the gold impregnation method for vitamin A-storing lipid droplets in hepatic stellate cells. Droplet morphometry was performed under oil immersion, and the calculated volumes plotted on computerized maps. The heterogeneous results were assessed with five concentric zones and five radial regions; the latter were determined based on midseptum visualized by portal injection. Zonation and regionation thus subdivided lobules into 5-zone/5-region (5Z/5R) compartmentalization. Distribution of values exhibited a distinct zonal gradient, heightened at peripheral zones 1 and 2, decreased over intermediate zone 3 toward centrilobular zones 4 and 5; peak was always found at zone 2. Within a single zone, variations were obvious, forming a regional gradient. Values were significantly higher at periportal than midseptal regions. Digitized mapping showed that low values filled up centrilobular zones, whereas high values concentrated in periportal regions. Along the periphery, inlet venules were quantified, revealing an occurrence rate of 60% at periportal, and 5% at midseptal regions, closely compatible with the regional gradient of vitamin A-storing capacity. The interweaving between zonal and regional gradients results in a vitamin A-low territory, a compound area composed of centrilobular zones plus extensions into midseptal regions. Because the results could account for physiological and pathological events, we regard the 5Z/5R compartmentalization a model worth routine adoption for a precise description of any morphofunctionally demonstrable heterogeneity of the liver lobules. (HEPATOLOGY 1998;27:1098-1108.)Evidence has accumulated in the literature and established a unique biological nature of the liver called heterogeneity.

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Section: Vitamin a And Hepatic Fibrosismentioning

confidence: 67%

Section: Vitamin a And Hepatic Fibrosismentioning

confidence: 97%

Zonal and regional differences identified from precision mapping of vitamin a-storing lipid droplets of the hepatic stellate cells in pig liver: A novel concept of addressing the intralobular area of heterogeneity

1998

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“…In alcoholic liver disease, fibrosis begins around the central veins, and some reports have suggested that the obstruction or thickening of the terminal hepatic venules by fibrosis leads to portal hypertension. [24][25][26] NASH is well known to be histologically similar to alcoholic liver disease. If the same theory were to be applied to patients with NASH, the results of our study would support this theory.…”

Section: Simple Steatosismentioning

confidence: 99%

Measurement of spleen volume is useful for distinguishing between simple steatosis and early‐stage non‐alcoholic steatohepatitis

Suzuki

Kohno

Yoneda

et al. 2010

Hepatology Research

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“…Hepatic fibrosis is the main histological feature that accom-Experimental evidence indicates that the lipid peroxipanies the progression of alcoholic liver injury to cirrhosis dation of biological membranes is often associated with in chronic alcohol abusers. 1,2 Acetaldehyde, a potential prothe development of liver fibrosis. We have studied the oxidant factor linked to ethanol metabolism, has been proeffect of neutrophil-derived reactive oxygen species posed as a mediator of fibrogenesis in alcoholic liver disease.…”

mentioning

confidence: 99%

Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates collagen synthesis in human hepatic stellate cells: Role of nitric oxide

Casini

1997

Hepatology

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Hepatic fibrosis is the main histological feature that accomExperimental evidence indicates that the lipid peroxipanies the progression of alcoholic liver injury to cirrhosis dation of biological membranes is often associated with in chronic alcohol abusers. 1,2 Acetaldehyde, a potential prothe development of liver fibrosis. We have studied the oxidant factor linked to ethanol metabolism, has been proeffect of neutrophil-derived reactive oxygen species posed as a mediator of fibrogenesis in alcoholic liver disease. (ROS) on collagen synthesis by human hepatic stellateIn fact, an immunohistochemical association between acetalcells (HSC), the major source of collagen in the liver, in dehyde-protein adducts and extracellular matrix deposition a coculture system. Lipid peroxidation in the cocultures in alcohol-induced liver injury has been reported. of extracellular matrix components in the liver. 6,13-16 When ROS resulted in the early induction of lipid peroxidation isolated and cultured on plastic, they undergo spontaneous and was associated with a marked increase (threefold) transformation into myofibroblast-like cells, thereby mimickof procollagen I mRNA expression and synthesis. The ing in vitro 17 conditions that prevail in vivo after chronic addition of antioxidants, such as vitamin E or superoxalcohol consumption. [18][19][20] However, different mechanisms, ide dismutase (SOD), impaired this stimulation. The other than acetaldehyde-induced fibrogenesis, may be ininhibition of neutrophil NO formation by N G -monovolved in alcoholic hepatic fibrosis. Evidence coming from methyl-L-arginine made the ROS-induced stimulation of either experimental or clinical studies indicates that lipid procollagen I more evident. The addition of xanthine/ peroxidation of biological membranes is often associated with xanthine oxidase X/XO, a superoxide anion donor, to the development of liver fibrosis. [21][22][23][24][25] We have recently shown HSC cultures strongly increased procollagen I synthesis.that the induction of lipid peroxidation phenomena or that This stimulation was hampered by the addition of both treatment with 4-hydroxynonenal (a highly reactive alde-SOD and sodium nitroprusside (an NO donor). The conhydic end-product of lipid peroxidation) stimulates procollatribution of HSC to the production of NO in our coculgen type I synthesis in human HSC by acting at the level ture system was negligible, because inducible NO synof gene expression. 26 Moreover, malondialdehyde has been thase (iNOS) mRNA was almost undetectable in these shown to stimulate collagen production by rat HSC upon acticells, and also because the amount of NO produced by vation in primary culture. 27 HSC stimulated with tumor necrosis factor a (TNF-a)Although alcoholic liver fibrosis may develop in the absence and lipopolysaccharide (LPS) was 500 times less than of evident inflammation, 1,2 the occurrence of alcoholic hepatithat synthesized by neutrophils. In conclusion, these retis may contribute to the increased extracellular matrix deposults ind...

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Perivenular Fibrosis in Alcoholic Liver Injury: Ultrastructure and Histologic Progression

Cited by 232 publications

References 23 publications

Zonal and regional differences identified from precision mapping of vitamin a-storing lipid droplets of the hepatic stellate cells in pig liver: A novel concept of addressing the intralobular area of heterogeneity

Zonal and regional differences identified from precision mapping of vitamin a-storing lipid droplets of the hepatic stellate cells in pig liver: A novel concept of addressing the intralobular area of heterogeneity

Measurement of spleen volume is useful for distinguishing between simple steatosis and early‐stage non‐alcoholic steatohepatitis

Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates collagen synthesis in human hepatic stellate cells: Role of nitric oxide

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