PILOT STUDY OF PIRFENIDONE IN PBC AND PSC

原发性胆汁性肝硬化（PBC）和原发性硬化性胆管炎（PSC） 进行性慢性胆汁淤积性肝病。 许多患者 最终发展为肝硬化和/或门静脉高压并死亡 除非肝移植介入，否则由肝功能衰竭引起。 没有 已经证明，特定的治疗在这些疾病中是完全有效的。 疾病熊去氧胆酸（UDCA）是最有前途的药物， PBC患者，但有些患者仍然会出现并发症， 肝脏疾病，需要肝移植。 没有有效 尽管对几种药物进行了评估，但仍对PSC进行了药物治疗。 是 因此，很明显，进一步的临床试验评估新药， PBC和PSC的治疗是必要的。 转化生长因子-β 1（TGF-β 1），一种生长细胞因子，在肿瘤的发展中起着关键作用。 实验性胆道和肝纤维化的动物模型。 吡非尼酮是一种TGF-β 1拮抗剂，是一种很有前途的新型抗肝纤维化药物 已经在实验和临床试验中进行了评估， 治疗其他非肝脏疾病，其特征在于过度 纤维化 本试验的目的是：（1）监测 PBC和PSC患者中吡非尼酮的特征，（2）比较 吡非尼酮相对于基线值对症状、肝脏的影响 生化和肝病并发症的发展， 评价吡非尼酮的临床抗肝纤维化活性 门静脉高压症（肝静脉压力梯度和 胃食管静脉曲张）， PSC患者胆管纤维化/硬化的严重程度。 PBC合并门脉高压症20例， PSC将接受吡非尼酮800 mg p.o. tid至少一个 最多两年 将基线值与观察到的值进行比较 治疗一年后。 有希望的结果将鼓励我们 在未来的大规模试验中， 大规模随机对照试验。我们的最终目标是能够 为这些患者提供安全有效的肝病治疗， 这是一个我们尚未实现的目标。

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are progressive chronic cholestatic liver diseases. Many patients eventually develop cirrhosis and/or portal hypertension with death caused by hepatic failure unless liver transplantation intervenes. No specific therapy has been proven to be totally effective in these diseases. Ursodeoxycholic acid (UDCA) is the most promising drug for patients with PBC but some patients still develop complications of their liver disease and require liver transplantation. There is no effective medical therapy for PSC despite evaluation of several drugs. It is clear therefore, that further clinical trials evaluating new drug in the treatment of PBC and PSC are needed. Transforming growth factor-beta 1 (TGF-B1), a growth cytokine, has a key role in the development of experimental biliary and hepatic fibrosis in animal models. Pirfenidone, a TGF-B 1 antagonist, is a promising new antifibrotic drug that has been evaluated in experimental and clinical trials in the treatment of other non-hepatic disease characterized by excessive fibrosis. The aims of this pilot study are: (1) to monitor the safety profile of pirfenidone in patients with PBC and PSC, (2) to compare the effects of pirfenidone to baseline values on symptoms, liver biochemistries and the development of complications of liver disease, and (3) to evaluate the clinical antifibrotic activity of pirfenidone on portal hypertension (hepatic venous pressure gradient and gastroesophageal varices) in portal hypertensive patients with PBC and on the severity of bile duct fibrosis/sclerosis in patients with PSC. Twenty PBC patients with portal hypertension and twenty patients with PSC will be treated with pirfenidone 800 mg p.o. tid for at least one and up to two years. Baseline values will be compared to those observed after treatment for one year. Promising results will encourage us to test this agent alone or in combination with other drugs in future large scale randomized controlled trials. Our ultimate aim is to be able to offer these patients safe and effective therapy for their liver disease, a goal which we have not yet achieved.