title: Fibrinogen and D-dimer levels elevate in advanced hepatocellular carcinoma: High pretreatment fibrinogen levels predict poor outcomes.
abstract: OBJECTIVE
  Plasma fibrinogen and D-dimer have been reported to predict survival in several types of malignancies. The aim of this study is to investigate their predictive value in patients with hepatocellular carcinoma (HCC).
  
  
  METHODS
  We retrospectively analyzed plasma fibrinogen and D-dimer levels from 252 subjects: control (n = 20), hepatitis (n = 20), cirrhosis (n = 20), and HCC (n = 192) subjects. The clinical involvement and prognostic value of fibrinogen and D-dimer was analyzed in HCC subjects. To confirm the effects of tumor on hypercoagulability and fibrinolysis, fibrinogen and D-dimer levels were measured in nude mice following HCC inoculation.
  
  
  RESULTS
  Fibrinogen decreased and D-dimer increased in cirrhosis subjects relative to other groups. In HCC subjects, elevated fibrinogen and D-dimer levels were significantly associated with adverse tumor features (increased size, stage, and grade) and systemic inflammation. Patients with HCC with either elevated fibrinogen or D-dimer levels had significantly higher 3-year tumor recurrence rates (65% vs. 41%, P < 0.001 for fibrinogen; 67% vs. 40%, P = 0.011 for D-dimer) and significantly lower 3-year overall survival rates (57% vs. 79%, P < 0.001 for fibrinogen; 56% vs. 80%, P = 0.001 for D-dimer). After multivariate analysis, elevated fibrinogen levels remained an independent predictor of poor prognosis in HCC patients. Finally, elevated levels of fibrinogen and D-dimer were confirmed in nude mice following tumor inoculation.
  
  
  CONCLUSIONS
  The fibrinogen and D-dimer levels, elevating after carcinogenesis, may serve as simple but effective predictors of adverse tumor profiles and outcomes in HCC.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Guo
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.
authors.forename: Qiaonan
authors.initials: Q
authors.lastname: Shan
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
keywords: D-dimer; HCC; fibrinogen; prognosis