PILOT STUDY OF PIRFENIDONE IN PBC AND PSC

原发性胆汁性肝硬变和原发性硬化性胆管炎 是进行性慢性胆汁淤积性肝病。很多病人 最终发展为肝硬变和/或门脉高压并死亡 由肝功能衰竭引起，除非肝移植介入。不是 特定的疗法已被证明对这些疾病完全有效。 疾病。熊去氧胆酸(UDCA)是治疗癌症最有前途的药物 患者患有PBC，但一些患者仍会出现并发症 肝脏疾病，需要肝移植。没有有效的方法 尽管对几种药物进行了评估，但仍对PSC进行了药物治疗。它是 因此，很明显，进一步的临床试验评估新药在 需要对PBC和PSC进行治疗。转化生长因子-β 1(转化生长因子-β1)是一种生长细胞因子，在肿瘤的发生发展中起关键作用。 实验性胆汁和肝纤维化动物模型。 转化生长因子-β1拮抗剂吡非尼酮是一种很有前途的抗纤维化新药 已经在实验和临床试验中对其进行了评估 以过度为特征的其他非肝病的治疗 纤维化症。这项先导研究的目的是：(1)监测安全 吡非尼酮在PBC和PSC患者中的分布，(2)比较 吡非尼酮对基线值的影响 生物化学和肝病并发症的发展， (3)评价吡非尼酮的临床抗纤维化作用 门静脉高压症(肝静脉压力梯度和 门静脉高压症合并PBC和门静脉高压症患者的胃-食道静脉曲张 PSC患者胆管纤维化/硬化程度的研究 20例PBC门脉高压症患者和20例门静脉高压症患者 PSC用吡非尼酮800 mg，P.O.至少一个TID 以及长达两年的监禁。基线值将与观测值进行比较 经过一年的治疗。有希望的结果将鼓励我们 今后可单独或与其他药物联合测试该制剂。 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.