VENOOCCLUSIVE DISEASE OF THE LIVER AFTER MARROW TRANSPLANTATION - HISTOLOGICAL CORRELATES OF CLINICAL SIGNS AND SYMPTOMS

We evaluated the relationship between the signs and symptoms of the clinical syndrome called venocclusive disease of the liver after bone marrow transplantation and the histological findings in 76 patients who later came to autopsy. Coded necropsy liver was scored for individual histological features that were correlated with prospectively assessed clinical features that the patients had exhibited during life. Patients were stratified into two groups: those with severe clinical venocclusive disease (n = 32) and those without. Clinically severe venocclusive disease was statistically correlated with several zone 3 acinar changes: occluded hepatic venules, the frequency of occluded hepatic venules x degree of occlusion, cccentric luminal narrowing/phlebosclerosis, zone 3 sinusoidal fibrosis and zone 3 hepatocyte necrosis (all p less than or equal to 0.03). There was a significant relationship between the number of these histological abnormalities in zone 3 of the liver acinus and a clinical diagnosis of severe venocclusive disease (p = 0.003). The presence of ascites was significantly correlated with occluded venules, zone 3 sinusoidal fibrosis and zone 3 hepatocyte necrosis (p = 0.001). Maximum serum bilirubin in the first 20 days after transplant was significantly correlated with sinusoidal fibrosis, hepatocyte necrosis and eccentric luminal sclerosis/phlebosclerosis (p < 0.01) but not with venular occlusion. The clinical syndrome of liver toxicity (commonly called venocclusive disease) that results from cytoreductive therapy before bone marrow transplant is strongly correlated with a constellation of histological lesions involving structures in zone 3 of the liver acinus and the hepatic venules into which sinusoidal blood flows. This study suggests that there is no single diagnostic histological feature. The severity of clinical venocclusive disease appears to be proportional to the number of such histological changes and is not due solely to occlusion of small hepatic venules.