Single determination of C-reactive protein at the time of diagnosis predicts long-term outcome of patients with hepatocellular carcinoma

Authors

  • Wolfgang Sieghart,

    1. Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria
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  • Matthias Pinter,

    1. Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria
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  • Florian Hucke,

    1. Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria
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  • Ivo Graziadei,

    1. Department of Internal Medicine II, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria
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  • Maximilian Schöniger-Hekele,

    1. Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria
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  • Christian Müller,

    1. Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria
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  • Wolfgang Vogel,

    1. Department of Internal Medicine II, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria
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  • Michael Trauner,

    1. Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria
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  • Markus Peck-Radosavljevic

    Corresponding author
    1. Department of Internal Medicine III, Division of Gastroenterology/Hepatology, Medical University of Innsbruck, Vienna, Austria
    • Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology/Hepatology; Währinger Gürtel 18-20, 1090 Vienna, Austria
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    • fax: +431 40400 3403.


  • Potential conflict of interest: Nothing to report.

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. Conclusion: 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)

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