Shulman H M, Fisher L B, Schoch H G, Henne K W, McDonald G B
Department of Pathology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Hepatology. 1994 May;19(5):1171-81.
We evaluated the relationship between the signs and symptoms of the clinical syndrome called veno-occlusive 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 veno-occlusive disease (n = 32) and those without. Clinically severe veno-occlusive disease was statistically correlated with several zone 3 acinar changes: occluded hepatic venules, the frequency of occluded hepatic venules x degree of occlusion, eccentric luminal narrowing/phlebosclerosis, zone 3 sinusoidal fibrosis and zone 3 hepatocyte necrosis (all p < or = 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 veno-occlusive 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 veno-occlusive 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 veno-occlusive disease appears to be proportional to the number of such histological changes and is not due solely to occlusion of small hepatic venules.
我们评估了76例后来接受尸检的患者中，骨髓移植后称为肝静脉闭塞病的临床综合征的体征和症状与组织学检查结果之间的关系。对编码的尸检肝脏进行评分，评估与患者生前前瞻性评估的临床特征相关的个体组织学特征。患者被分为两组：临床严重肝静脉闭塞病患者（n = 32）和无该病患者。临床严重肝静脉闭塞病与几个3区腺泡改变在统计学上相关：肝小静脉闭塞、肝小静脉闭塞频率×闭塞程度、偏心管腔狭窄/静脉硬化、3区窦状隙纤维化和3区肝细胞坏死（所有p≤0.03）。肝腺泡3区这些组织学异常的数量与严重肝静脉闭塞病的临床诊断之间存在显著关系（p = 0.003）。腹水的存在与小静脉闭塞、3区窦状隙纤维化和3区肝细胞坏死显著相关（p = 0.001）。移植后前20天的最高血清胆红素与窦状隙纤维化、肝细胞坏死和偏心管腔硬化/静脉硬化显著相关（p < 0.01），但与小静脉闭塞无关。骨髓移植前细胞减灭治疗导致的肝毒性临床综合征（通常称为肝静脉闭塞病）与一系列涉及肝腺泡3区结构和窦状隙血流汇入的肝小静脉的组织学病变密切相关。这项研究表明不存在单一的诊断性组织学特征。临床肝静脉闭塞病的严重程度似乎与这类组织学改变的数量成正比，并非仅由肝小静脉闭塞所致。
