title: A unique bleeding-related complication of sorafenib, a tyrosine kinase inhibitor, in advanced hepatocellular carcinoma: a case report.
abstract: BACKGROUND
  Sorafenib, a multikinase inhibitor as a standard of care for advanced hepatocellular carcinoma, may lead endothelial cells to an unstable state by blocking the signaling pathway of vascular endothelial growth factor receptor, which may result in the disruption of the architecture and integrity of the microvasculature, and eventually increase the risk of hemorrhage. Hemobilia is a relatively uncommon condition as a consequence of hepatocellular carcinoma and its risk factors remain uncertain.
  
  
  METHODS
  Here we report a unique case of hemobilia occurring in a 55-year-old Korean man with hepatitis B virus-related hepatocellular carcinoma on Barcelona Clinic Liver Cancer advanced stage after seven days of treatment with sorafenib. He had received prior radiation therapy. Endoscopy revealed bleeding from the major duodenal papilla and endoscopic retrograde cholangiography revealed an amorphous filling defect throughout the common bile duct. Blood clots were removed by balloon sweeping and a nasobiliary drainage tube was placed. No further bleeding has been detected as of eight months after discontinuation of sorafenib.
  
  
  CONCLUSIONS
  Sorafenib may increase the risk of biliary bleeding in hepatocellular carcinoma patients who were primed with irradiation, by blocking the signaling pathway of the vascular endothelial growth factor receptor. Therefore, sorafenib should be used with caution in patients with advanced hepatocellular carcinoma, especially when combined with radiation therapy.
authors.forename: Ha Yan
authors.initials: HY
authors.lastname: Kang
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Division of Hepatology, Department of Internal Medicine, Dankook University College of Medicine, 16-5 Anseo-dong, Cheonan 330-715, Chungnam, Republic of Korea. ihsong21@dankook.ac.kr.
authors.forename: Il Han
authors.initials: IH
authors.lastname: Song