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
Know-how and research interests
Liver cirrhosis represents one of the most common causes 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/hormonal mechanisms. Thus, the development of new treatment options to reverse the structural, functional, and hemodynamic 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) playing a pivotal role 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. Angiogenesis seems to be closely connected to the process of 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. A key area in the study of the cellular and molecular relationships between fibrogenesis and angiogenesis concerns the pro-angiogenic role of activated HSC.
Liver sinusoidal remodeling, hepatic fibrogenesis and portal hypertension
Techniques and infrastructure of the research group
- CCl4 model (toxic cirrhosis with portal hypertension): Carbon tetrachloride (CCl4) is administered by a dorsal subcutaneous injection, or gavage. Sixteen weeks after administration of CCl4, micronodular cirrhosis and portal hypertension has developed.
- PPVL model (isolated portal hypertension without cirrhosis): The model of partial portal vein ligation (PPVL) has been used to study splanchnic hemodynamics, angiogenesis and hyperdynamic circulation in prehepatic PHT 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 cirrhosis after 28 days. BDL animals also develop a hepato-pulmonary syndrome (HPS) characterized by intrapulmonary vasodilation and right-left shunting resulting in impaired oxygenation.
- Measurement of portal pressure: Cannulation of an ileocolonic vene or the splenic pulp.
- Measurement of mean arterial pressure and heart rate: cannulation of the femoral or carotid artery
- Measurement of porto-systemic shunting: injection of radioactive or colored microspheres in the portal vein, calculation of porto-systemic collateral blood flow via the ratio lung/(liver+lung)
- Measurement of splanchnic blood flow: non-constrictive ultrasound flow probe placed on superior or inferior mesenterial artery
- Measurement of central venous pressure: cannulation of the internal jugular vein.
- Measurement of intrapulmonary shunting: injection of radioactive or colored microspheres in the internal jugular vein, calculation of theintrapulmonary shunting via 1- ratio (lung/injected activity).
5 selected publications
1. Reiberger T, Aberle JH, Kundi M, Rieger A, Gangl A, Holzmann H, Peck-Radosavljevic M
„IP-10 correlates with HCV viral load, hepatic inflammation and fibrosis and predicts HCV response, relapse or non-response in HIV-HCV co-infection”
Antiviral Therapy 2008; 13: 969-976
2. Reiberger T, Angermayr B,Schwabl P, Rohr-Udilova N, Mitterhauser M, Gangl A, Peck-Radosavljevic M
„Sorafenib attenuates the portal hypertensive syndrome in partial portal vein ligated rats“
Journal of Hepatology 2009; 51: 865-873
3. Reiberger T, Ferlitsch A, Sieghart W, Kreil A, Breitenecker F, Rieger A, Schmied B, Gangl A, Peck-Radosavljevic M
“HIV-HCV co-infected patients with low CD4+ cell nadirs are at risk for faster fibrosis progression and portal hypertension”
Journal of Viral Hepatitis 2010; 17(6): 400-409
4. Reiberger T, Payer BA, , Schwabl P, Horvatits T, Jäger B, Hummel T, Mitterhauser M, Trauner M, Fuhrmann V, Angermayr B, Peck-Radosavljevic M (Vienna Hepatic Experimental Hemodynamic Lab)
"Nebivolol deteriorates portal hemodynamics in cirrhotic rats by increasing splanchnic blood flow”
Liver International (accepted December 2012)
5. Pinter M, Sieghart W, Reiberger T, Rohr-Udilova N, Ferlitsch A, Peck-Radosavljevic M
„The effects of sorafenib on the portal hypertensive syndrome in patients with liver cirrhosis and hepatocellular carcinoma – a pilot study“
Alimentary Pharmacology and Therapeutics 2012;35(1):83-91