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Published in: Journal of Gastroenterology 9/2012

01-09-2012 | Original Article—Liver, Pancreas, and Biliary Tract

Portal hemodynamic effects of sorafenib in patients with advanced hepatocellular carcinoma: a prospective cohort study

Authors: Hisashi Hidaka, Takahide Nakazawa, Toru Kaneko, Tsutomu Minamino, Juichi Takada, Yoshiaki Tanaka, Yusuke Okuwaki, Masaaki Watanabe, Akitaka Shibuya, Wasaburo Koizumi

Published in: Journal of Gastroenterology | Issue 9/2012

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Abstract

Background and aims

Sorafenib is currently in clinical use as an oral multikinase inhibitor that blocks tumor growth and cell proliferation in advanced hepatocellular carcinoma (HCC). It has been demonstrated in a translating study that sorafenib had a beneficial effect on portocollateral circulation in cirrhotic animals with portal hypertension. This study was prospectively performed to evaluate the portal hemodynamic effect of sorafenib in patients with advanced HCC using duplex Doppler ultrasonography (DDU).

Methods

Twenty-five Child-Pugh class-A patients with advanced HCC had received sorafenib at a dose of 400 mg twice daily. Primary outcomes were changes in portal venous area (PVA; cm2) as seen by using DDU before and after a 2-week administration of sorafenib. Secondary outcomes included the changes of laboratory data and other flow data revealed on DDU.

Results

PVA was significantly decreased after a 2-week administration (0.78 ± 0.23 vs. 0.64 ± 0.25, P = 0.023), while the portal venous flow velocity (PVV; cm/s) was not significantly changed (0.22 ± 0.06 vs. 0.24 ± 0.07, P = 0.17). Therefore, the congestion index (PVA/PVV), which reflects the pathophysiological hemodynamics of portal venous system, was significantly decreased (3.9 ± 1.7 vs. 3.0 ± 1.4, P = 0.042).

Conclusions

We demonstrated the portal hemodynamic effect of sorafenib in patients with advanced HCC. Considering that this was a short-term study, because sorafenib could be a potential beneficial therapeutic agent for portal hypertension, it will be necessary to verify its clinical benefits for portal hypertension in future studies.
Literature
1.
go back to reference Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Bland JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRef Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Bland JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008;359:378–90.PubMedCrossRef
2.
go back to reference Cheng AL, Kang YK, Chen Z, Tasao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.PubMedCrossRef Cheng AL, Kang YK, Chen Z, Tasao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10:25–34.PubMedCrossRef
3.
go back to reference Mejias M, Garcia-Pras E, Tiani C, Miquel R, Bosch J, Fernandez M, et al. Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats. Hepatology. 2009;49:1245–56.PubMedCrossRef Mejias M, Garcia-Pras E, Tiani C, Miquel R, Bosch J, Fernandez M, et al. Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats. Hepatology. 2009;49:1245–56.PubMedCrossRef
4.
go back to reference Garcia-Tsao G, Bosch J, Groszmann RJ. Portal hypertension and variceal bleeding—unresolved issues. Summary of an American Association for the study of liver diseases and European Association for the study of the liver single-topic conference. Hepatology. 2008;47:1764–72.PubMedCrossRef Garcia-Tsao G, Bosch J, Groszmann RJ. Portal hypertension and variceal bleeding—unresolved issues. Summary of an American Association for the study of liver diseases and European Association for the study of the liver single-topic conference. Hepatology. 2008;47:1764–72.PubMedCrossRef
5.
go back to reference Perelló A, Escorsell A, Bru C, Gilabert R, Moitinho E, Garcia-Pagan JC, et al. Wedged hepatic venous pressure adequately reflects portal pressure in hepatitis C virus-related cirrhosis. Hepatology. 1999;30:1393–7.PubMedCrossRef Perelló A, Escorsell A, Bru C, Gilabert R, Moitinho E, Garcia-Pagan JC, et al. Wedged hepatic venous pressure adequately reflects portal pressure in hepatitis C virus-related cirrhosis. Hepatology. 1999;30:1393–7.PubMedCrossRef
6.
go back to reference Sabbà C, Merkel C, Zoli M, Ferraioli G, Gaiani S, Sacerdoti D, et al. Interobserver and interequipment variability of echo-Doppler examination of the portal vein: effect of a cooperative training program. Hepatology. 1995;21:428–33.PubMed Sabbà C, Merkel C, Zoli M, Ferraioli G, Gaiani S, Sacerdoti D, et al. Interobserver and interequipment variability of echo-Doppler examination of the portal vein: effect of a cooperative training program. Hepatology. 1995;21:428–33.PubMed
7.
go back to reference Bolognesi M, Sacerdoti D, Merkel C, Gerunda G, Maffei-Faccioli A, Angeli P, et al. Splenic Doppler impedance indices: influence of different portal hemodynamic conditions. Hepatology. 1996;23:1035–40.PubMedCrossRef Bolognesi M, Sacerdoti D, Merkel C, Gerunda G, Maffei-Faccioli A, Angeli P, et al. Splenic Doppler impedance indices: influence of different portal hemodynamic conditions. Hepatology. 1996;23:1035–40.PubMedCrossRef
8.
go back to reference Moriyasu F, Nishida O, Ban N, Nakamura T, Sakai M, Miyake T, et al. “Congestion index” of the portal vein. Am J Roentgenol. 1986;146:735–9. Moriyasu F, Nishida O, Ban N, Nakamura T, Sakai M, Miyake T, et al. “Congestion index” of the portal vein. Am J Roentgenol. 1986;146:735–9.
9.
go back to reference The Liver Cancer Study Group of Japan. The general rules of the clinical and pathological study of primary liver cancer. 2nd ed. Tokyo: Kanehara; 2003. The Liver Cancer Study Group of Japan. The general rules of the clinical and pathological study of primary liver cancer. 2nd ed. Tokyo: Kanehara; 2003.
10.
go back to reference Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.PubMedCrossRef Lencioni R, Llovet JM. Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis. 2010;30:52–60.PubMedCrossRef
11.
go back to reference Coriat R, Gouya H, Mir O, Ropert S, Vignaux O, Chaussade S, et al. Reversible decrease of portal venous flow in cirrhotic patients: a positive side effect of sorafenib. PLoS ONE. 2011;6:e16978.PubMedCrossRef Coriat R, Gouya H, Mir O, Ropert S, Vignaux O, Chaussade S, et al. Reversible decrease of portal venous flow in cirrhotic patients: a positive side effect of sorafenib. PLoS ONE. 2011;6:e16978.PubMedCrossRef
12.
go back to reference 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. J Hepatol. 2009;51:865–73.PubMedCrossRef 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. J Hepatol. 2009;51:865–73.PubMedCrossRef
13.
go back to reference Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125–34.PubMedCrossRef Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Siebels M, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007;356:125–34.PubMedCrossRef
Metadata
Title
Portal hemodynamic effects of sorafenib in patients with advanced hepatocellular carcinoma: a prospective cohort study
Authors
Hisashi Hidaka
Takahide Nakazawa
Toru Kaneko
Tsutomu Minamino
Juichi Takada
Yoshiaki Tanaka
Yusuke Okuwaki
Masaaki Watanabe
Akitaka Shibuya
Wasaburo Koizumi
Publication date
01-09-2012
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 9/2012
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-012-0563-6

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