The Early Lesions of Veno-occlusive Disease of the Liver

Abstract

A disease characterized by ascites and hepatomegaly was described in Jamaica by McFarlane and Branday in 1945, and later studied by Hill and his colleagues (Hill, Rhodes, Stafford and Aub, 1953), and by Bras, Jelliffe and Stuart (1954). Bras and his co-workers demonstrated occlusion of the small hepatic veins and accordingly named the condition 'Veno-occlusive disease of the liver' (V.O.D.). The exact nature of the occlusions has not been ascertained, although Bras and his colleagues likened some of them to an obliterating endophlebitis, and others to organized mural thrombi.The death of three children early in the disease, one three days, another five days and a third 21 days after the onset of symptoms has prompted us to reinvestigate the pathogenesis of what are believed to be early lesions. Materials and MethodsFormal-saline fixed liver tissue was available from all three cases. Paraffin sections were prepared in the usual way and stained with haematoxylin and eosin (H. and E.). Other staining methods used were Mallory's trichrome (M.T.), Mallory's phosphotungstic acid haematoxylin (M.P.A.H.), and Wilder's method for reticulin. One block from each case was sectioned serially, and initially every fifth section was stained. Other sections were stained when indicated.Fresh material was available from the case dying at 21 days permitting the use of the immuno-histochemical techniques described by Coons, Creech, Jones andBerliner (1942), andCoons and Kaplan (1950). Blocks of liver tissue were frozen in a dry-ice alcohol mixture and stored at -20°C. Sections were cut in a cryostat at temperatures between -20°C. to -10°C. and mounted in the cold on glass slides. They were washed with two changes of phosphate buffer, pH 7*2, and covered with rabbit anti-human fibrin serum conjugated with fluorescein isocyanate. After staining for 30 minutes they were washed repeatedly in the phosphate buffer and mounted in buffered glycerol (pH 8 0). The anti-human fibrin serum was prepared by immunizing rabbits with human fibrin. The fibrin was * Present address: King's College Hospital, London S.E.5. teased, cut into fine fragments, suspended in Freund's adjuvant and injected subcutaneously. Three doses of 1 g. fibrin were given at intervals of 10 days, and the rabbits were bled three days after the last injection. The globulins were precipitated from the rabbit serum by saturation with anhydrous sodium-sulphate and the precipitate redissolved in distilled water and transferred to a dialysing bag and the sodium sulphate removed. The globulin was then coupled with fluorescein isocyanate and the labelled antiserum treated with powdered rat liver to reduce non-specific staining. The specificity of the antiserum was checked by demonstrating a single precipitation band in an Ouchterlony plate; by staining obvious fibrin deposits in placental tissue; and by treating duplicate sections with fluorescein-coupled antihuman fibrin serum absorbed with washed human fibrin. The sections were examined with the fluorescent microscope, photographe...

Toxic Factors in Veno‐occlusive Disease

“…in humans. When large single doses were given by mouth, acute necrosis resulted, as described from our laboratory (for instance, by Stirling and Urquhart, 1962), a development analogous to that described earlier by several authors ( e . g .…”

“…(1) Some, apparently very sensitive to the toxin, died approximately 48 hours after Crotalaria ingestion, with an acute centrilobular liver cell necrosis, such as described by Stirling and Urquhart, 1962. ( 2 ) Others died at around the fifth to the eighth days. Estimations of serum glutamic pyruvic transaminase ( S.G.P.T.…”

Sinusoidal Obstruction Syndrome (Hepatic Veno-Occlusive Disease)

“…In the early 1960's, studies of the effects of ionizing radiation on mammalian tissues documented that the hepatic vasculature could be damaged by this mechanism, 3 in the absence of antecedent vascular thrombosis. 4,5 The most striking example of an obliterative venous lesion induced by irradiation was documented in humans with lung tumors receiving radiation treatment; both the lung vasculature and that of the dome of the liver that was included in the radiation field developed vascular obliteration, but not the remainder of the unexposed liver. 6 Shortly thereafter, induction of obliterative venopathy following heavy irradiation directly of the human liver for metastatic disease was reported in 12 patients receiving upper abdominal irradiation by the Stanford Linear Accelerator.…”

Study of an epidemic of venoocclusive disease in India.

“…Obliterative lesions of the smallest centrilobular and sublobular hepatic veins diagnostic of well-established VOD (Bras, 1973) were not seen in the biopsies and were observed only at necropsy in one patient who died in the present series. Stirling et al (1962), using histological and immunofluorescent techniques, have shown that, in early VOD, fibrin may immediately surround the hepatic vein radicles and apparently obstruct the inflow of blood from the sinusoids. The obliterative lesion could be secondary to an interruption of the blood supply (Rappaport et al, 1969).…”