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 cl inical syndrome called venocclusive disease of the liver after bone ma rrow 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. Patien ts were stratified into two groups: those with severe clinical venoccl usive disease (n = 32) and those without. Clinically severe venocclusi ve disease was statistically correlated with several zone 3 acinar cha nges: occluded hepatic venules, the frequency of occluded hepatic venu les x degree of occlusion, cccentric luminal narrowing/phlebosclerosis , zone 3 sinusoidal fibrosis and zone 3 hepatocyte necrosis (all p les s 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 occlu ded venules, zone 3 sinusoidal fibrosis and zone 3 hepatocyte necrosis (p = 0.001). Maximum serum bilirubin in the first 20 days after trans plant was significantly correlated with sinusoidal fibrosis, hepatocyt e necrosis and eccentric luminal sclerosis/phlebosclerosis (p < 0.01) but not with venular occlusion. The clinical syndrome of liver toxicit y (commonly called venocclusive disease) that results from cytoreducti ve 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 bloo d flows. This study suggests that there is no single diagnostic histol ogical feature. The severity of clinical venocclusive disease appears to be proportional to the number of such histological changes and is n ot due solely to occlusion of small hepatic venules.