Pathogenesis of veno-occlusive liver disease after radiation

Abstract

Radiation-induced liver disease is characterized structurally by progressive fibrous obliteration of central veins (veno-occlusive disease [VOD]). The pathogenesis is unknown. Samples of liver from 11 patients with radiation-induced VOD were studied by light and electron microscopy for evidence of central vein thrombosis. The patients had received fractionated radiation with total doses of 1,850 to 4,050 rads, or single doses of 1,000 rads. In addition, six patients had received chemotherapy. Although usually undetectable by light microscopy, fibrin was found in all samples, sometimes in large amounts, within central veins, and also often in the adjacent sinusoids. One sample had a small platelet aggregate. In two patients, portal veins also showed occlusive lesions. We postulate that ionizing radiation injures preferentially the endothelial cells of central veins, which leads to focal deposition of fibrin. The resulting fibrin network is eventually replaced by collagen, causing fibrous occlusion. In several patients, this type of liver injury occurred at radiation doses conventionally considered safe even in the absence of chemotherapy.