title: Portal hemodynamic effects of sorafenib in patients with advanced hepatocellular carcinoma: a prospective cohort study.
abstract: OBJECTIVE
  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; cm(2)) 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.
authors.affiliation: Department of Gastroenterology, Internal Medicine, Kitasato University East Hospital, 2-1-1 Asamizodai, Minami-ku, Sagamihara, Kanagawa 252-0380, Japan. hisashi7@kitasato-u.ac.jp
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hidaka
authors.forename: Takahide
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Toru
authors.initials: T
authors.lastname: Kaneko
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Minamino
authors.forename: Juichi
authors.initials: J
authors.lastname: Takada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuwaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Akitaka
authors.initials: A
authors.lastname: Shibuya
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008099:Liver / Q000502:physiology; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011169:Portal Vein / Q000502:physiology; D011446:Prospective Studies; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome; D018616:Ultrasonography, Doppler, Duplex
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib