Dr. Philipp Schwabl
MedUni Wien RESEARCHER OF THE MONTH June 2018
The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction
Patients with liver cirrhosis often develop complications related to portal hypertension such as ascites, variceal bleeding and hepatic encephalopathy. Treatment of portal hypertension thus, represents a key component in the management of cirrhotic patients. Yet, only half of patients respond to the current standard therapy with non-selective beta blockers.
The farnesoid X receptor (FXR) regulates bile acid homeostasis and lipid metabolism in the liver and – as shown in our work – modulates the vascular tone of the hepatic microvasculature, i.e. the hepatic sinusoids. In cirrhotic animal models, pharmacological activation of FXR (using PX-20606) decreased vasoconstriction of the hepatic sinusoids and thus, reduced portal pressure. Most importantly, hepatic FXR activation also reduced liver fibrosis and hepatic inflammation. These experimental data clearly show that FXR agonists such as PX-20606 ameliorate several critical components of portal hypertension and represent a promising treatment option for patients with liver cirrhosis.
The effects of the FXR agonists are currently being investigated in trails including patients with non-alcoholic steatohepatitis (NASH) and cholestatic liver diseases. Recently, the FXR agonist obeticholic acid has been approved for treatment of primary biliary cholangitis (PBC).
- Schwabl P, Hambruch E, Seeland BA, Hayden H, Wagner M, Garnys L, et al. The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction. Journal of AHepatology 2016. (IF 12.486)
- Schwabl P, Bota S, Salzl P, Mandorfer M, Payer BA, Ferlitsch A, et al. New reliability criteria for transient elastography increase the number of accurate measurements for screening of cirrhosis and portal hypertension. Liver international 2015;35:381-390. (IF 4.116)
- Schwabl P, Bucsics T, Soucek K, Mandorfer M, Bota S, Blacky A, et al. Risk factors for development of spontaneous bacterial peritonitis and subsequent mortality in cirrhotic patients with ascites. Liver international 2015;35:2121-2128. (IF 4.116)
- Schwabl P*, Mandorfer M*, Steiner S, Scheiner B, Chromy D, Herac M, et al. Interferon-free regimens improve portal hypertension and histological necroinflammation in HIV/HCV patients with advanced liver disease. Alimentary Pharmacology & Therapeutics 2017;45:139-149. (IF 7.286)
- Mandorfer M, Bota S, Schwabl P, Bucsics T, Pfisterer N, Kruzik M, et al. Nonselective beta blockers increase risk for hepatorenal syndrome and death in patients with cirrhosis and spontaneous bacterial peritonitis. Gastroenterology 2014;146:1680-1690 e1681. (IF 18.187)
- Fuchs CD*, Schwabl P*, Reiberger T, Trauner M. Liver Capsule: FXR agonists against liver disease. Hepatology 2016;64:1773. (IF 13.246)
- Schwabl P*, Payer BA*, Grahovac J, Klein S, Horvatits T, Mitterhauser M, et al. Pioglitazone decreases portosystemic shunting by modulating inflammation and angiogenesis in cirrhotic and non-cirrhotic portal hypertensive rats. Journal of Hepatology 2014;60:1135-1142. (IF 12.486)
- Reiberger T, Angermayr B, Schwabl P, Rohr-Udilova N, Mitterhauser M, Gangl A, et al. Sorafenib attenuates the portal hypertensive syndrome in partial portal vein ligated rats. Journal of Hepatology 2009;51:865-873. (IF 12.486)
- Schwabl P, Laleman W. Novel treatment options for portal hypertension. Gastroenterology report 2017;5:90-103.
- Mandorfer M*, Schwabl P*, Steiner S, Scheiner B, Chromy D, Bucsics T, et al. Interferon-free treatment with sofosbuvir/daclatasvir achieves sustained virologic response in 100% of HIV/hepatitis C virus-coinfected patients with advanced liver disease. Aids 2016;30:1039-1047. (IF 5.554)
* equal cotribution