Division of Paediatric Oncology, Catholic University of Rome, Rome, Italy.
Paediatr Drugs. 2010 Oct 1;12(5):277-84. doi: 10.2165/11531840-000000000-00000.
Hepatic veno-occlusive disease (VOD) is a major manifestation of liver toxicity associated with conventional and high-dose chemotherapy in children affected by hematologic malignancies and certain solid tumors. Clinically, patients present with jaundice, painful hepatomegaly, and fluid retention, which may evolve into multi-organ failure, a hallmark of severe disease. The pathogenesis is complex and not completely understood, but the damage to sinusoidal endothelium, typically caused by toxic metabolites released from antineoplastic drugs, is thought to play a crucial role, together with cytokine activation, immune deregulation, and coagulopathy. Diagnosis is based on clinical criteria supported by characteristic ultrasound findings, with the gold standard investigation being hepatic-venous pressure gradient measurement and biopsy. Several treatment options have been tested; the most convincing approach to date is the use of defibrotide, a novel oligonucleotide with antithrombotic and antiplatelet aggregating properties, as well as endothelial-stabilizing effects. This agent, together with other specific forms of supportive care, has shown efficacy in the treatment of established VOD and promising results in the prevention of VOD in pediatric patients receiving chemotherapy.
肝静脉闭塞病（VOD）是与血液系统恶性肿瘤和某些实体瘤患儿接受常规和高剂量化疗相关的肝毒性的主要表现。临床上，患者表现为黄疸、肝痛和体液潴留，可能进展为多器官衰竭，这是严重疾病的标志。发病机制复杂，尚未完全阐明，但认为窦状内皮损伤，通常由抗肿瘤药物释放的毒性代谢物引起，与细胞因子激活、免疫失调和凝血异常一起起关键作用。诊断基于临床标准，并支持特征性超声发现，金标准检查是肝静脉压力梯度测量和活检。已经测试了几种治疗选择；迄今为止最有说服力的方法是使用新型寡核苷酸药物 defibrotide，它具有抗血栓和抗血小板聚集以及稳定内皮的特性。该药物与其他特定形式的支持性护理一起，已显示出在治疗已确立的 VOD 方面的疗效，并在预防接受化疗的儿科患者的 VOD 方面显示出有希望的结果。
