Priv. Doz. Dr. Thomas Reiberger
Associate Professor of Hepatology
Medical University of Vienna
Department of Internal Medicine III
Div. of Gastroenterology & Hepatology
Vienna Hepatic Experimental Hemodynamic Lab
Waehringer Guertel 18-20, 1090 Vienna, Austira
Phone: +43 (0)1 40400 - 4744
Fax: +43 (0)1 40400 - 4735
HEPEX Lab at MedUniWien
HEPEX Lab at CeMM and LBI-RUD
Know-how and research interest
Liver disease, especially when progressed to advanced fibrosis or cirrhosis represents a major cause of death in the Western world. More recently, hepatic fibrosis has been redefined as a highly dynamic process involving fibrogenesis, matrix degradation, angiogenesis and metabolic and immunological mechanisms. Abnormal remodeling of the hepatic sinusoidal vasculature represents a hallmark cirrhosis. Thus, the development of new treatment options to improve the structural (matrix), functional (synthesis), and hemodynamic (vascular) abnormalities in liver cirrhosis is encouraged. Portal hypertension (PHT) is defined as an elevated pressure in the portal venous system that may cause severe complications such as formation of gastroesophageal varices, variceal bleeding, development of ascites, occurrence of bacterial translocation, hepatic encephalopathy, systemic vasodilation, and hyperdynamic circulation. Increased intrahepatic vascular resistance is the hallmark of sinusoidal PHT with hepatic stellate cells (HSCs) and liver sinusoidal endothelial cells (LSECs) playing pivotal roles in this process. HSCs transform from quiescent, vitamin A-storing subendothelial cells to myofibroblast-like cells endowed with contractile, proinflammatory, and fibrogenic properties. Pathological angiogenesis is involved in the development of increased portal inflow and pressure as well as the formation of portosystemic collaterals and is closely linked to hepatic fibrogenesis: First, fibrogenesis is characterized by an over-expression of several growth factors, cytokines and matrix metalloproteinases (MMPs) with an inherent pro-angiogenic action. In particular, platelet-derived growth factor (PDGF), transforming growth factor-β1 (TGF-β1), fibroblast growth factor (FGF) and VEGF have been shown to act both as pro-fibrogenic and pro-angiogenic mediators. Furthermore, neo-angiogenesis is stimulated in hepatic tissue by the progressive increase of tissue hypoxia due to progressive capillarization of sinusoids and excessive matrix deposition with consequent up-regulation of proangiogenic pathways. My lab thus focuses on the characterization of structural, functional, vascular and hemodynamic abnormalities characterizing advanced liver disease in order to develop novel treatment strategies.
Hepatic microenvironment in liver disease focusing on fibrogenesis, angiogenesis, sinusoidal vascular remodeling and portal hypertension.
Techniques and infrastructure of the research group
- CCl4 model (toxic cirrhosis with portal hypertension): Due to repetitive administration of the hepatotoxic agent carbon tetrachloride (CCl4) micronodular liver fibrosis, cirrhosis and portal hypertension are induced
- PPVL model (isolated portal hypertension without cirrhosis): Due to partial portal vein ligation (PPVL) a sudden increase in portal pressure is induced that affects splanchnic hemodynamics, angiogenesis and hyperdynamic circulation as seen in prehepatic portal hypertension without hepatic dysfunction.
- BDL model (cholestatic cirrhosis with hepato-pulmonary syndrome): The common bile duct is ligated and resected resulting in progressive cholestasis and inflammation ultimately leading to fibrosis and cirrhosis. BDL animals also develop a hepato-pulmonary syndrome (HPS) characterized by intrapulmonary vasodilation and right-left shunting resulting in impaired oxygenation.
- NASH model: different diets, usually characterized by high-fat (HFD) or methionine-choline deficient (MCD) content are administered in order to induce metabolic liver disease that may progress to fibrosis and cirrhosis with portal hypertension
- Measurement of portal pressure by invasive cannulation of an ileocolonic vein or the splenic pulp.
- Measurement of systemic hemodynamics, heart rate and arterial pressures by invasive cannulation of the femoral or carotid artery
- Measurement of portosystemic shunting (PSS) by injection of radioactive or colored microspheres in the portal vein or the splenic pulp followed by the measurement of the fractions of microspheres going to the capillary beds of the lung and the liver.
- Measurement of splanchnic arterial and portal venous blood flow by using non-constrictive perivascular ultrasound flow probes placed on superior or inferior mesenterial artery or the portal vein.
- Measurement of central venous pressure by invasive cannulation of the internal jugular vein.
- Measurement of intrapulmonary shunting by injection of radioactive or colored microspheres in the internal jugular vein, measurement of the fractions of microspheres going to the capillary beds of the lung and subsequent calculation of the intrapulmonary shunting via 1- ratio (lung/injected activity).
1. „Sorafenib attenuates the portal hypertensive syndrome in partial portal vein ligated rats“ by Reiberger T, Angermayr B,Schwabl P, Rohr-Udilova N, Mitterhauser M, Gangl A, Peck-Radosavljevic M. Journal of Hepatology 2009; 51: 865-873
2. "Nebivolol deteriorates portal hemodynamics in cirrhotic rats by increasing splanchnic blood flow” by Reiberger T, Payer BA, , Schwabl P, Horvatits T, Jäger B, Hummel T, Mitterhauser M, Trauner M, Fuhrmann V, Angermayr B, Peck-Radosavljevic M. Liver International 2013;33(4):561-568
3. „The effects of sorafenib on the portal hypertensive syndrome in patients with liver cirrhosis and hepatocellular carcinoma – a pilot study“ by Pinter M, Sieghart W, Reiberger T, Rohr-Udilova N, Ferlitsch A, Peck-Radosavljevic M. Alimentary Pharmacology and Therapeutics 2012;35(1):83-91
4. “An orthotopic mouse model of hepatocellular carcinoma with underlying liver cirrhosis” by Reiberger T, Chen Y, Ramjiawan RR, Hato T, Fan C, Samuel R, Roberger S, Huang P, Lauwers GY, Zhu AX, Bardeesy N, Jain RK, Duda DG. Nature Protocols 2015;10(8):1264-74.
5. “The FXR agonist PX20606 ameliorates portal hypertenision by targeting vascular remodeling and sinusoidal dysfunction” by Schwabl P, Hambruch E, Seeland BA, Hayden H, Wagner M, Garnys L, Strobel B, Schubert TL, Riedl F, Mittereggger D, Burnet M, Starlinger P, Oberhuber G, Deuschle U, Rohr-Udilova N, Podesser BK, Peck-Radosavljevic M, Reiberger T, Kremoser C, Trauner M. J Hepatol 2017; 66(4):724-733
6. “The soluble guanylate cyclase stimulator riociguat reduces fibrogenesis and portal pressure in cirrhotic rats” by Schwabl P, Brusilovskaya K, Supper P, Bauer D, Königshofer P, Riedl F, Hayden H, Fuchs CD, Stift J, Oberhuber G, Aschauer S, Bonderman D, Gnad T, Pfeifer A, Uschner FE, Trebicka J, Rohr-Udolova N, Podesser BK, Peck-Radosavljevic M, Trauner M, Reiberger T. Sci Rep. 2018 Jun 19;8(1):9372