The effects of sorafenib on the portal hypertensive syndrome in patients with liver cirrhosis and hepatocellular carcinoma – a pilot study
Article first published online: 27 OCT 2011
© 2011 Blackwell Publishing Ltd
Alimentary Pharmacology & Therapeutics
Volume 35, Issue 1, pages 83–91, January 2012
How to Cite
Pinter, M., Sieghart, W., Reiberger, T., Rohr-Udilova, N., Ferlitsch, A. and Peck-Radosavljevic, M. (2012), The effects of sorafenib on the portal hypertensive syndrome in patients with liver cirrhosis and hepatocellular carcinoma – a pilot study. Alimentary Pharmacology & Therapeutics, 35: 83–91. doi: 10.1111/j.1365-2036.2011.04896.x
- Issue published online: 9 DEC 2011
- Article first published online: 27 OCT 2011
- Publication data Submitted 22 July 2011 First decision 30 August 2011 Resubmitted 3 September 2011 Accepted 3 October 2011 EV Pub Online 27 October 2011
Aliment Pharmacol Ther 2012; 35: 83–91
Background Increased intrahepatic vascular resistance and hyperperfusion in the splanchnic circulation are the principal mechanisms leading to portal hypertension in cirrhosis. Several preclinical studies have demonstrated a beneficial effect of the multikinase inhibitor sorafenib on the portal hypertensive syndrome.
Aim To investigate the effect of sorafenib on hepatic venous pressure gradient (HVPG), systemic hemodynamics and intrahepatic mRNA expression of proangiogenic, profibrogenic and proinflammatory genes.
Methods Patients with liver fibrosis/cirrhosis and hepatocellular carcinoma were treated with sorafenib 400 mg b.d. HVPG measurement and transjugular liver biopsy were performed at baseline and at week 2. Changes in HVPG and intrahepatic mRNA expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), RhoA, tumour necrosis factor-alpha (TNF-α) and placental growth factor (PlGF) were evaluated.
Results Thirteen patients (m/f = 12/1; Child–Pugh class A/B = 10/3) were included. The most common aetiology of liver disease was alcohol consumption (n = 7). Eleven patients had an elevated portal pressure, including eight patients with clinically significant portal hypertension. A significant decrease of HVPG (≥ 20% from baseline) was observed in four subjects. In HVPG responders, we observed mRNA downregulation of VEGF, PDGF, PlGF, RhoA kinase and TNF-α, while no substantial mRNA decrease was found in nonresponders in any of the five genes. In two of the four HVPG responders we observed a dramatic (43–85%) mRNA decrease of all five investigated genes.
Conclusion Larger controlled clinical trials are needed to demonstrate any potential beneficial effect of sorafenib on portal hypertension in patients with cirrhosis.