PILOT STUDY OF PIRFENIDONE IN PBC AND PSC

Summary

Principal Investigator: Keith Lindor
Abstract: 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.
Funding Period: 1998-09-25 - 2000-07-31
more information: NIH RePORT

Top Publications

  1. pmc The predictors of the presence of varices in patients with primary sclerosing cholangitis
    Sombat Treeprasertsuk
    Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, USA
    Hepatology 51:1302-10. 2010

Detail Information

Publications1

  1. pmc The predictors of the presence of varices in patients with primary sclerosing cholangitis
    Sombat Treeprasertsuk
    Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, USA
    Hepatology 51:1302-10. 2010
    ..The platelet count of 205 (x 10(9)/L) and the total bilirubin level of 1.7 mg/dL were the best cutoff values for the detection of new varices...