去纤苷在治疗肝小静脉闭塞病这方面效果怎么样？

Defibrotide (sodium defibrotide) is currently recognized as the most promising new drug for the treatment of hepatic veno-occlusive disease (HVOD) after hematopoietic stem cell transplantation (HSCT). It is a single-stranded oligonucleotide mixture with anti-thrombotic and fibrinolysis-promoting effects. It was approved for marketing in the EU in October 2013 and was approved for marketing in the United States by the U.S. Food and Drug Administration (FDA) on March 30, 2016.

How effective is defibrotide in the treatment of hepatic veno-occlusive disease?

In a phase 2 trial of 75 patients, a phase 3 trial of 102 patients, and an expansion trial of an additional 351 patients, all patients in the trial were diagnosed with hepatic VOD with renal or pulmonary dysfunction after HSCT. In the phase 2 trial, 44% of patients survived 100 days after transplantation, compared with 38% in the phase 3 trial and 45% in the expanded trial, and the FDA noted in a report that the expected 100-day survival rate in patients with severe hepatic VOD who were not treated with defibrotide was 21%-31%.

Based on its anticoagulant, fibrinolysis-promoting, and anti-inflammatory effects, Richardson et al. first explored the application of defibrotide (defibrotide sodium) in the treatment of HVOD after HSCT. This study included 19 sHVOD patients. The dosage of defibrotide is 5~60mg/kg per day, intravenous infusion, and the median usage time is 15d (2-61d). The results showed that 42% of patients achieved complete remission (CR), and the overall survival (os) rate 100 days after transplantation reached 32%, and patients could tolerate defibrination well. Since then, multiple clinical trials have confirmed the effectiveness of defibrotide in the treatment of HVOD.

In terms of safety, the side effects of defibrotide are relatively mild, with only 4% of patients discontinuing treatment due to side effects. Of note, defibrination increases plasmin activity in vitro, and sputum may increase the risk of bleeding after hematopoietic stem cell transplantation (HSCT) in patients with VOD. Do not initiate defibrotide in patients with active bleeding.