奥沙利铂相关肝窦阻塞综合征研究进展

Research progress of sinusoidal obstruction syndrome associated with oxaliplatin

奥沙利铂(OXA)为第3代铂类抗癌药,主要用于转移性结直肠癌的治疗。肝窦阻塞综合征(SOS)是OXA常见且较严重的不良反应,主要临床表现为脾肿大、血小板减少、肝功能异常和门静脉高压等。其发生机制与OXA诱导肝脏氧化应激反应和炎症反应,造成肝窦内皮细胞损伤,进而导致肝窦内血小板聚集和血管阻塞等密切相关。SOS的发生与OXA累积剂量和治疗周期有关,脾肿大是OXA相关SOS发生的独立预测因子,血小板减少、血清透明质酸水平升高和天冬氨酸转氨酶/血小板比值指数升高也可预测SOS的发生。既往有慢性肝病尤其是存在门静脉高压者须慎用OXA。OXA治疗期间应警惕SOS的发生,出现可疑SOS的症状应及时进行影像学检查,早期诊断、及时停药有利于肝纤维化逆转,严重肝纤维化的患者预后较差。

Oxaliplatin(OXA)is the third⁃generation platinum antineoplastic agents,mainly used in the treatment of metastatic colorectal cancer.Sinusoidal obstruction syndrome(SOS)is a common and serious adverse reaction of OXA.The main clinical manifestations are splenomegaly,thrombocytopenia,abnormal liver function,and portal hypertension.The mechanism is closely related to OXA⁃induced oxida⁃tive stress and inflammatory reactionsin the liver,which lead to injury of hepatic sinusoidal endothelial cells,and then lead to platelet aggregation and vascular obstruction in hepatic sinusoids.The occurrence of SOS is related to the accumulated dose and the treatment cycle of OXA.Splenomegaly is an independent predic⁃tor of OXA⁃related SOS.Thrombocytopenia,elevated serum hyaluronic acid and aspartate aminotransferase⁃to⁃platelet ratio index can also predict the occurrence of SOS.OXA should be used with caution in patients with chronic liver disease,especially in those with portal hypertension.Special attention should be paid to the occurrence of SOS during OXA treatment.For patients with symptoms of suspicious SOS,imaging examination should be performed in time.Early diagnosis and timely withdrawal of drugs are beneficial for the reversal of liver fibrosis,and the prognosis of patients with severe fibrosis is poor.