title: Single determination of C-reactive protein at the time of diagnosis predicts long-term outcome of patients with hepatocellular carcinoma.
abstract: We investigated the prognostic value of C-reactive protein (CRP) in patients with hepatocellular carcinoma (HCC) not amenable to surgery. A total of 615 patients diagnosed with HCC not amenable to surgery between April 1999 and December 2009 at the Department of Gastroenterology of the Medical Universities of Vienna and Innsbruck were included. We assessed the optimal CRP cutoff by regression spline analysis and tested its impact on median overall survival (OS) by the Kaplan-Meier method, univariate analysis (log-rank test), and multivariate analysis (Cox proportional hazard regression model) in a training cohort (n = 466, Vienna) and an independent validation cohort (n = 149, Innsbruck). We found a sigmoid-shaped association of CRP and the hazard ratio of death upon regression spline analysis and defined a CRP level <1/≥1 mg/dL as optimal cutoff for further survival assessments. Elevated CRP (≥1 mg/dL) at diagnosis was associated with poor OS (CRP-elevated versus CRP-normal; 4 versus 20 months; P < 0.001) and remained a significant negative predictor for OS upon multivariate analysis (hazard ratio, 1.7; P < 0.001), which was independent of age, Child-Pugh class, tumor characteristics, and treatment allocation. Analyses with respect to Barcelona Clinic Liver Cancer (BCLC) stage and Child-Pugh class supported the relevance of CRP (BCLC-stage C and Child-Pugh A: OS for CRP-elevated versus CRP-normal, 6 versus 14; P < 0.001; BCLC-stage C and Child-Pugh B: OS for CRP-elevated versus CRP-normal, 4 versus 15 months; P < 0.001). The prognostic significance of elevated CRP was reproducible at a second CRP determination timepoint and confirmed in the independent validation cohort.
  
  
  CONCLUSIONS
  Elevated CRP is associated with a dismal prognosis in HCC patients and may become a useful marker for patient selection in HCC management. (HEPATOLOGY 2012).
authors.affiliation: Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sieghart
authors.forename: Matthias
authors.initials: M
authors.lastname: Pinter
authors.forename: Florian
authors.initials: F
authors.lastname: Hucke
authors.forename: Ivo
authors.initials: I
authors.lastname: Graziadei
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schöniger-Hekele
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vogel
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D002423:Cause of Death; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein