Fan Cathy Q, Crawford James M
Hofstra North Shore-LIJ School of Medicine, North Shore-LIJ Health System, Manhasset, NY, USA.
J Clin Exp Hepatol. 2014 Dec;4(4):332-46. doi: 10.1016/j.jceh.2014.10.002. Epub 2014 Oct 30.
Hepatic sinusoidal obstruction syndrome (SOS) is an obliterative venulitis of the terminal hepatic venules, which in its more severe forms imparts a high risk of mortality. SOS, also known as veno-occlusive disease (VOD), occurs as a result of cytoreductive therapy prior to hematopoietic stem cell transplantation (HSCT), following oxaliplatin-containing adjuvant or neoadjuvant chemotherapy for colorectal carcinoma metastatic to the liver and treated by partial hepatectomy, in patients taking pyrrolizidine alkaloid-containing herbal remedies, and in other particular settings such as the autosomal recessive condition of veno-occlusive disease with immunodeficiency (VODI). A central pathogenic event is toxic destruction of hepatic sinusoidal endothelial cells (SEC), with sloughing and downstream occlusion of terminal hepatic venules. Contributing factors are SEC glutathione depletion, nitric oxide depletion, increased intrahepatic expression of matrix metalloproteinases and vascular endothelial growth factor (VEGF), and activation of clotting factors. The clinical presentation of SOS includes jaundice, development of right upper-quadrant pain and tender hepatomegaly, ascites, and unexplained weight gain. Owing to the potentially critical condition of these patients, transjugular biopsy may be the preferred route for liver biopsy to exclude other potential causes of liver dysfunction and to establish a diagnosis of SOS. Treatment includes rigorous fluid management so as to avoid excessive fluid overload while avoiding too rapid diuresis or pericentesis, potential use of pharmaceutics such as defibrotide, coagulolytic agents, or methylprednisolone, and liver transplantation. Proposed strategies for prevention and prophylaxis include reduced-intensity conditioning radiation for HSCT, treatment with ursodeoxycholic acid, and inclusion of bevacizumab with oxaliplatin-based chemotherapeutic regimes. While significant progress has been made in understanding the pathogenesis of SOS and in mitigating against its adverse outcomes, this condition remains a serious complication of a selective group of medical treatments.
肝窦阻塞综合征（SOS）是终末肝小静脉的闭塞性静脉炎，病情较重时死亡率很高。SOS也称为静脉闭塞性疾病（VOD），发生于造血干细胞移植（HSCT）前的减瘤治疗后、含奥沙利铂的辅助或新辅助化疗用于肝转移结直肠癌并接受部分肝切除术后、服用含吡咯里西啶生物碱草药的患者以及其他特殊情况，如伴有免疫缺陷的静脉闭塞性疾病（VODI）这一常染色体隐性疾病。一个核心致病事件是肝窦内皮细胞（SEC）的毒性破坏，伴有终末肝小静脉的脱落和下游阻塞。促成因素包括SEC谷胱甘肽耗竭、一氧化氮耗竭、基质金属蛋白酶和血管内皮生长因子（VEGF）肝内表达增加以及凝血因子激活。SOS的临床表现包括黄疸、右上腹疼痛和肝肿大压痛、腹水以及不明原因的体重增加。由于这些患者病情可能危急，经颈静脉活检可能是肝活检的首选途径，以排除肝功能障碍的其他潜在原因并确诊SOS。治疗包括严格的液体管理，以避免液体过多负荷，同时避免过度快速利尿或腹腔穿刺放液，可能使用诸如去纤苷、促凝溶解剂或甲泼尼龙等药物，以及肝移植。预防和 prophylaxis的建议策略包括降低强度的HSCT预处理放疗、熊去氧胆酸治疗以及在基于奥沙利铂的化疗方案中加入贝伐单抗。虽然在理解SOS的发病机制和减轻其不良后果方面已取得重大进展，但这种情况仍然是一组选择性医疗治疗的严重并发症。
