Fibrosis perisinusoidal

Various infectious, toxic or immunological lesions lead to a presinusoidal block in adults. From a primary endothelial lesion, endophlebitis ensues. Rich in fibres and deficient in cells, it is ultimately responsible for the obliteration and even disappearance of the portal branches. Obliterative portal venopathy (N.C. Nayak et al., 1969) with portal and periportal fibrosis and subsequent perisinusoidal sclerosis is referred to as hepatoportal sclerosis (W P. Mikkelsen et al., 1965). This is a complex disorder involving splenomegaly, hypersplenism and portal hypertension, which has also been described as non-cirrhotic portal fibrosis (XL. Boyer et al., 1967) or idiopathic portal hypertension (K. Okuda et al., 1982). (I2l, 127) Band s syndrome (7) probably fell into this group ... 

Vitamin A intoxication Prolonged and marked vitamin A intoxication leads to a substantial increase in individual Ito cells. This in turn causes constriction of the sinusoids the accompanying fatty degeneration of the hepatic cells supports this obstructive effect. The Ito cells are responsible for perisinusoidal fibrosis. The liver surface is strikingly smooth despite marked portal hypertension (often with considerable oesophageal varices). (119) (s. figs. 14.2, 14.3)... 

Fig. 14.2 Slight lobular inflammation. Periportal/perisinusoidal delicate fibrosis as a result of chronic vitamin A intoxication (same patient as in fig. 14.3) (Ladewig)...

Fig. 21.16 Perivenular and perisinusoidal fine-meshed fibrosis and discreet cellular inflammatory reaction as a result of chronic alcohol abuse (CV = central vein) (Ladewig)...

Medicinal agents (such as contraceptives) may result in proliferations of the intima in the hepatic artery and its branches. In some cases, these arterial alterations were associated with thrombosis in the hepatic veins. Phar-macons can trigger three different forms of damage to the sinusoids (7.) dilation of the sinusoids (e.g. by contraceptives), (2.) perisinusoidal fibrosis (e.g. by azathio-prine, vitamin A and cytostatic agents), and (i.) peliosis hepatis (e. g. by contraceptives, anabolic and androgenic steroids, azathioprine, chenodesoxycholic acid). (13, 28, 130) (s. p. 398) (s. fig. 21.8)... 

Fig. 30.3 Thorotrast liver deposits of thorotrast in portal and perisinusoidal macrophages periportal fibrosis and inflammation...

Labadie, H., Stoessel, P., Callard, P., Beaugrand, M. Hepatic venooc-clusive disease and perisinusoidal fibrosis secondary to arsenic poisoning. Gastroenterology 1990 99 1140-1143... 

Mannosidosis, first observed by P.-A. Ockerman in 1967, is caused by a-mannosidase deficiency. The gene defect (autosomal recessive) is localized on chromosome 19p, 13, 2-ql2. Hepatospleno-megaly, steatosis and perisinusoidal fibrosis are in evidence. PAS-positive vacuoles, consisting of lysosomally stored substances, are found in the cytoplasm of the hepatocytes. 

Liver biopsies have been performed in some patients with chronic vitamin A intoxication. Perisinusoidal fibrosis and massive accumulation of lipid-storing cells were found. Impairment of blood flow by perisinusoidal fibrosis probably resulted in secondary alterations in hepato-cytes, including cellular atrophy and formation of cytoplasmic bullae. Histological examination also showed central vein sclerosis and focal congestion associated with perisinusoidal storage. The vitamin A concentration in the liver was increased (40-42). 

A 51-year-old man, with a 9-year history of renal insufficiency and an alcohol intake of 4 U/week, underwent transplant nephrectomy. At surgery, ascites and liver cirrhosis were noted. A needle biopsy of the liver 1 month later showed nodular regenerative hyperplasia but no cirrhosis. There were subendothehal vacuolated cells, suggestive of modified stellate cells, and there was adjacent focal perisinusoidal fibrosis. His medications included one multivitamin/mineral supplement per day containing vitamin A 4000 lU. His vitamin A concentration was 1045 (reference range 490-720) ng/ml. Viral and antibody studies were negative. 

The hepatic stellate (or Ito) cells are fat-storing cells found in the perisinusoidal spaces between the hepatocytes and sinusoids these cells can later become involved in hepatic fibrosis. When hepatic lipid is increased by greater than 5% by weight, the histological changes are described as steatosis, or fatty changes. 

Perisinusoidal Ito cells (fat-storing cells, hepatic h-pocytes, vitamin A-storing cells) are the primary matrix-producing cells in liver fibrosis. They are difficult to visualize in standard histological preparations but can be identified in sections of rat liver by immunohistochemical detection of the intermediate filament protein desmin this protein is not expressed by other sinusoidal cells (Yokoi etal. 1984, Burt etal. 1986). 

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