REIBERGER Thomas, M.D.

Research Interests: Liver Fibrosis, Portal Hypertension, Angiogenesis, Viral Hepatitis

Hepatic fibrosis is the consequence of most types of chronic liver diseases (CLDs) and the common-endpoint cirrhosis represents one of the most common causes of death in the Western world. Currently, there are no effective therapies to treat liver fibrosis in patients in which the causative agent cannot be removed (e.g. patients after antiviral treatment with successful eradication of chronic hepatitis C virus infection) and mortality rates still remain unacceptably high. Considering these epidemiological data, the socioeconomic impact of liver cirrhosis is extraordinary. Liver cirrhosis was traditionally regarded as a “point-of-no-return” end-stage disease. More recently, hepatic fibrosis has been redefined as a highly dynamic process involving fibrogenesis, matrix degradation, angiogenesis and metabolic/hormonal mechanisms. Portal hypertension (PHT) is defined as an elevated pressure in the portal venous system 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 are related to PHT. 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. The sinusoidal endothelium is distinguished by openings (fenestrations) that, together with discontinuities in the basement membrane, are essential for proper permeability through this unique low resistance/low pressure microvascular network.  Accordingly, matrix deposition within the space of Disse and closure of endothelial fenestrations – processes that together underlie sinusoidal capillarization - impede the rapid exchange of solutes between the sinusoidal space and hepatocytes, causing increased resistance to portal blood flow and PHT. In addition, the process of capillarization of intrahepatic sinusoids as found in cirrhotic livers may impair hepatic metabolism and may influence cellular and humoral signaling by altered vascular permeability. In summary, several structural, functional, hemodynamic, and abnormalities can be found in cirrhotic livers which may be all considered when assessing potential therapeutic targets for reversing liver fibrosis and sinusoidal remodeling.

Methods & Technique

Research experience in labor animal care, isolated rat liver perfusion, liver cell isolation, hepatocyte-couplets culture, confocal life-cell microscopy, surface fluorescence measurements, IF microscopy.

Vienna Hepatic Experimental Hemodynamic (HEPEX) Lab: Mouse and rat models of liver fibrosis, mouse and rat models of biliary cirrhosis, mouse and rat models of non-cirrhotic portal hypertension, hemodynamic measurements of splanchnic and portal blood flow, porto-systemic shunting, intrapulmonary shunting, and systemic and portal pressure.

Vienna Hepatic Hemodynamic Laboratory: hepativ-venous pressure gradient, right-heart catheterization, transjugular liver biopsy, hepatic vein blood sampling.

Selected Publications 

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 51: 865-873, 2009

Reiberger T, Kosi L, Maresch J, Breitenecker F, Payer BA, Wrba F, Rieger A, Gangl A, Peck-Radosavljevic M: Mitochondrial toxicity is associated with virological response in HIV-HCV coinfected patients treated with Ribavirin and HAART. Journal of Infectious Diseases 202: 156-160, 2010

Reiberger T, Ferlitsch A, Payer BA, Pinter M, Schwabl P, Stift J, Trauner M, Peck-Radosavljevic M: Noninvasive screening for liver fibrosis and portal hypertension by transient elastography - a large single center experience. Wiener Klinische Wochenschrift 124: 395-402, 2012

Reiberger T, Payer BA, Ferlitsch A, Sieghart W, Breitenecker F, Aichelburg MC, Schmied B, Rieger A, Trauner M, Peck-Radosavljevic M: A prospective evaluation of pulmonary, systemic and hepatic hemodynamics in HCV-HIV coinfected patients prior and after antiviral therapy with pegylated interferon and ribavirin. Antiviral Therapy 2012 Sep 5 (Epub, doi 10.3851/IMP2349, PMID: 22948263)

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 35: 83-91, 2012

Mandorfer M, Reiberger T, Payer BA, Ferlitsch A, Breitenecker F, Aichelburg MC, Obermayer-Pietsch B, Rieger A, Trauner M, Peck-Radosavljevic M (Vienna HIV & Liver Study Group): Low vitamin D levels are associated with impaired virologic response to PEGIFN+RBV therapy in HIV/HCV coinfected patients. AIDS 2012 Oct 1 (Epub, PMID: 22032421)