毒理性
在接受奥沙利铂治疗的病人中，有相当一部分人会出现轻度和短暂的血清转氨酶水平升高，但它们与奥沙利铂的关系往往不明确。奥沙利铂化疗与肝脏的病理性变化有关，这些变化包括窦状扩张、充血和中央小叶坏死，这些都是窦状阻塞综合征的表现。这些变化通常在急性期时轻到中度，临床上并不显著，但它们可能进展为临床明显的窦状阻塞综合征，或者随着长期治疗，可能发展为结节性再生性增生，伴随脾大、血小板减少和食管静脉曲张。结节性再生性增生通常需要6到18个月的时间来发展，并且在奥沙利铂的化疗周期重复后出现。血清酶和胆红素升高最小，主要的实验室发现是持续进展的血小板减少，反映了脾大和门脉高压的发展。结节性再生性增生的第一个临床证据可能是腹水、食管静脉曲张出血或肝性脑病。尝试肝脏切除、严重胃肠道出血和败血症可能会触发肝功能失代偿和肝衰竭。有趣的是，一旦停止化疗，结节性再生性增生和门脉高压往往会缓慢改善，但这些变化的长远后果并不明确。
Mild and transient elevations in serum aminotransferase levels are found in an appreciable proportion of patients taking oxaliplatin, but their relationship to oxaliplatin is often unclear. Chemotherapy with oxaliplatin has been associated with histological changes in the liver marked by sinusoidal dilatation, congestion and centrolobular necrosis indicative of sinusoidal obstruction syndrome. These changes are usually mild-to-moderate in severity and not clinically significant during the acute phase, but they can progress to clinically apparent sinusoidal obstruction syndrome or, with chronic therapy, to nodular regenerative hyperplasia with splenomegaly, thrombocytopenia and esophageal varices. Nodular regenerative hyperplasia typically requires 6 to 18 months to develop and arises after repeated cycles of chemotherapy with oxaliplatin. Serum enzyme and bilirubin elevations are minimal, the major laboratory finding being a progressive and persistent thrombocytopenia reflecting the development of splenomegaly and portal hypertension. The first clinical evidence of nodular regenerative hyperplasia may be ascites, esophageal variceal hemorrhage or hepatic encephalopathy. Attempts at hepatic resection, severe gastrointestinal bleeding and septicemia may trigger hepatic decompensation and liver failure. Interestingly, nodular regenerative hyperplasia and portal hypertension tend to improve slowly once chemotherapy is stopped, but the long term consequences of the changes are not well defined.
来源:LiverTox
