Toxic Injury to Hepatic Sinusoids: Sinusoidal Obstruction Syndrome (Veno-Occlusive Disease)

Abstract

The term veno-occlusive disease of the liver refers to a form of toxic liver injury characterized clinically by the development of hepatomegaly, ascites, and jaundice, and histologically by diffuse damage in the centrilobular zone of the liver. The cardinal histologic features of this injury are marked sinusoidal fibrosis, necrosis of pericentral hepatocytes, and narrowing and eventual fibrosis of central veins. Recent studies suggest that the primary site of the toxic injury is sinusoidal endothelial cells, followed by a series of biologic processes that lead to circulatory compromise of centrilobular hepatocytes, fibrosis, and obstruction of liver blood flow. Thus we propose a more appropriate name for this form of liver injury--sinusoidal obstruction syndrome. This review encompasses historical perspectives, clinical manifestations of sinusoidal obstruction syndrome in the setting of hematopoietic cell transplantation, histologic features of centrilobular injury, and a discussion of the pathophysiology of sinusoidal injury, based on both animal and clinical investigations.

Inflammatory Modulation of Hepatocyte Apoptosis by Nitric Oxide: In Vivo, In Vitro, and In Silico Studies

“…[11] In vivo, hepatocyte iNOS expression has been identified in response to endotoxemia, [17] hemorrhagic shock, [18,19] hepatic and intestinal ischemia/reperfusion, [20] and during hepatic regeneration [21] or hepatitis. [22,23] Whereas acute insults result in a rapid but transient increase in iNOS expression, massive and sustained hepatocyte iNOS expression is observed following injection of killed Corynebacterium parvum. [24,25] This exuberant hepatic iNOS expression lasts for days with little evidence of hepatic injury.…”

“…However, in both models the temporal sequence of events support direct hepatocellular injury in the presence of iNOS. Expression of iNOS has also been shown to contribute to toxicity in models of alcohol-induced cirrhosis [23] and hepatitis induced by concanavalin A or acetaminophen. [22,29,30] These observations stand in contrast to studies in animal models of endotoxemia, [31,32] lipopolysaccharide/D-galactosamine (LPS/D-gal) administration, [33] hepatic regeneration [21] and cold ischemia/reperfusion following transplantation.…”

The role of the endothelium in the short-term complications of hematopoietic SCT

“…Thus, despite the possibility that other factors can contribute to VOD development, endothelial injury seems to be the initiating event in the cascade of events leading to clinical manifestation of this complication. [5][6][7] These observations of VOD, the fact that the pathogenesis of the remaining early complication seems to have a close relationship with the microvascular tree (Table 1), and their overlapping clinical manifestations (Table 2), are the main reasons these syndromes have been grouped under the denomination of vascular syndromes or vascular endothelial syndromes after HSCT.…”

Jet-fixation: A novel method to improve microscopy of human liver needle biopsies

“…As a result, it is impossible to study sinusoids and sinusoidal cells in human liver needle biopsies. This is an important disadvantage, because these cells play a key role in several pathophysiological mechanisms, such as cold ischemia, 11 drug-induced toxicity, 12 lipoprotein clearance, 13 and fibrosis. 14,15 There is a pressing need for properly fixed TEM material, as until now sinusoidal cells are mainly studied in human cell culture or animal models.…”