Pathologic aspects of cirrhosis

Pópper, Hans; Zak, Frederick G.

doi:10.1016/0002-9343(58)90298-5

Cited by 107 publications

(89 citation statements)

References 108 publications

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“…The issue remains regarding the reversibility of cirrhosis and this depends on the definition of cirrhosis. Popper and Zak [59] described cirrhosis as being characterized by an increase in the extracellular matrix, parenchymal changes, and has important functional consequences in contrast to simple fibrosis, which may be devoid of significant functional effects. They further highlighted this difference in a communication published in 1968, in which they defined cirrhosis as a process characterized by a clinically, functionally, and pathologically significant disturbance of hepatic circulation [60].…”

Section: Reversibility Of Hepatic Fibrosismentioning

confidence: 99%

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL)

et al. 2008

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Section: Reversibility Of Hepatic Fibrosismentioning

confidence: 99%

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL)

et al. 2008

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“…In studies with mice, immune complexes made the hepatic injuries worse [28]. Popper [29] suggested that hepatocellular necrosis was an important factor for the initiation of liver cirrhosis in humans. The fibrosis in PS-induced model, however, is characterized by absence of obvious hepatocellular necrosis [27], even in the early stage [8].…”

Section: Animalsmentioning

confidence: 99%

Morphological and Immunohistochemical Studies on Porcine Serum-Induced Rat Liver Fibrosis

Shiga

Shirota

Ikeda

et al. 1997

The Journal of Veterinary Medical Science

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ABSTRACT. In order to clarify the pathogenesis of porcine serum (PS)-induced rat liver fibrosis, three experiments differing in dose of PS or duration of treatment were performed on male Fischer 344 rats. The rats were given an intraperitoneal injection of PS twice a week for 3 to 16 weeks and euthanized 7 days after the last injection for each treatment group. Liver tissues from these animals were subjected to detailed morphological and immunohistochemical examinations. Biochemical tests on treated rat serum revealed an increase in globulin concentration but no elevation in AST, ALT and ALP activities. There were no relationships among the dose of PS, the extent of fibrosis, and the anti-PS antibody titer. A number of α-smooth muscle actin-positive non-myofibroblastic cells, desmin-positive cells, and lipofuscin-laden Kupffer cells were found around the central veins and in the fibrous septa. In advanced stages of fibrosis, a proliferation of elastic fibers were observed in the septa. These findings were considered to indicate gradually occurred hepatocellular necrosis. The vascular endothelial cells in the fibrous septa expressed factor VIII-related antigen, exhibited fenestration accompanied by basement membrane formation, and were surrounded by Ito cells. Most of the portal vein branches showed hypertrophic thickening of the smooth muscle layer, resulting in narrowing of the lumen. These vascular changes suggested that hemodynamic alterations of the intrahepatic circulation induced hepatocellular necrosis/apoptosis and played an important role in the pathogenesis of porcine serum-induced liver fibrosis in rats. MATERIALS AND METHODS Animals:Fifty, 7-week-old male rats (Fischer 344/NSlc, Japan SLC Inc., Shizuoka), weighing approximately 150 g, were given an intraperitoneal injection of PS (JRH Biosciences, Lunexa, KS, U.S.A., Lot No. 4C2028) twice a week. The same lot of PS was used throughout the study. The rats were housed (two or three per cage) in polycarbonate cages and maintained under controlled conditions (temperature, 23 ± 2°C; humidity, 60 ± 5%). A commercial diet (CE-7, CLEA Japan Inc., Tokyo) and tap water were supplied ad libitum. The rats were euthanized under ether anesthesia by exsanguination via the abdominal aorta 7 days after the last injection for each treatment group. The spleen weight was measured to investigate the presence of portal hypertension and the degree of reaction against PS injection, and the mean values for control and treated groups were subjected to statistical analysis with Student's t-test. Serum samples, obtained from rats at necropsy, were stored at 20°C until analyses for biochemistry and antibody titer against PS.Experiment I: This experiment was designed to investigate time-related morphological changes of fibrosis. Rats were injected with a 0.5 ml of PS twice weekly for 3, 4, 5, 6 or 7 weeks. Control rats received 0.5 ml of physiological saline. Two treated rats and two control rats were euthanized at the time points mentioned above.

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“…Vascular changes induced by severe previous insults are the source of physiologic disturbance, not only it is expressed as portal hypertension, but also as hepatic failure (Popper 1977). Thus, in schistosomiasis, portal vein obstructive lesions coupled to hepatic artery hypertrophy are the dominating vascular changes (Andrade & Cheever 1977), while in cirrhosis a complex of porto-hepatic shunts, hepatic artery hypertrophy, and sinusoidal capillarization are responsible for the deranged physiology (Popper 1977). Usually these important vascular changes have not been particularly considered during the process of fibrosis regression.…”

mentioning

confidence: 99%

Remodeling of hepatic vascular changes after specific chemotherapy of schistosomal periportal fibrosis

Andrade

Baptista

Santana

2006

Mem. Inst. Oswaldo Cruz

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Pathologic aspects of cirrhosis

Cited by 107 publications

References 108 publications

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL)

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL)

Morphological and Immunohistochemical Studies on Porcine Serum-Induced Rat Liver Fibrosis

Remodeling of hepatic vascular changes after specific chemotherapy of schistosomal periportal fibrosis

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