去纤苷治疗肝小静脉闭塞病效果如何？

For some patients with leukemia and lymphoma, hematopoietic stem cell transplantation (HSCT) is the only hope to cure the disease and regain health. Hepatic veno-occlusive disease (HVOD) is one of the serious complications after hematopoietic stem cell transplantation (HSCT), and the mortality rate in patients with severe HVOD can be as high as 100%. (Defibrotide, produced in Italy) is a single-stranded oligonucleotide mixture that has anti-thrombotic and fibrinolytic effects. In recent years, multiple clinical research results have shown that defibrotide is a safe and effective drug for preventing and treating HVOD.

In vitro, defibrinoside enhances the enzymatic activity of plasmin that hydrolyzes fibrin clots, increases tissue plasminogen activator (t-PA) and thrombomodulin expression, and decreases von Willebrand factor (vWF) and plasminogen activation inhibitor-1 (PAI-1) expression, thereby reducing EC activation and increasing EC-mediated fibrinolysis. Defibrotide protects ECs from chemotherapy, tumor necrosis factor-α (TNF-α), serum starvation, and perfusion-induced injury. 

In clinical trials, heparin was used to prevent diseases such as hepatic veno-occlusion while greatly increasing the risk of bleeding, while defibrinoside alone or in combination with heparin had a very low incidence of side effects and achieved good results in preventing HVOD. In a phase III multi-center randomized clinical trial completed in Europe, a total of 356 stem cell transplant patients were recruited. The incidence of hepatic vein occlusion 30 days after transplantation was compared. It was found that 2 of 180 patients in the defibrotide group developed hepatic vein occlusion, accounting for 12%; 35 of 176 patients in the control group developed hepatic vein occlusion, accounting for 20%. 

Defibrotide is the first drug approved by the FDA for the treatment of severe hepatic venule occlusion, a rare and fatal liver disease. The approval was based on 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 veno-occlusive disease and associated renal or pulmonary dysfunction after HSCT (hematopoietic stem cell transplantation). 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 for patients with untreated severe veno-occlusive disease was 21%-31%.