Source

Medical University of Vienna, Department of Internal Medicine III, Division of Gastroenterology/Hepatology.

Abstract

BACKGROUND:

We investigated the prognostic value of C-reactive protein (CRP) in patients with hepatocellular carcinoma (HCC) not amenable to surgery.

METHODS:

A total of 615 patients diagnosed with HCC not amenable to surgery between 04/1999 and 12/2009 at the Departments of Gastroenterology of the Medical Universities of Vienna and Innsbruck were included. We assessed the optimal CRP cut off 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).

RESULTS:

We found a sigmoid shaped association of CRP and the hazard ratio of death upon regression spline analysis and defined a CRP level <1/ò1 mg/dl as optimal cut off for further survival assessments. Elevated CRP (ò1 mg/dl) at diagnosis was associated with poor OS (CRP-elevated. vs. CRP-normal; 4 vs. 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 from 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 vs. CRP-normal, 6 vs. 14; P<0.001; BCLC-stage C and Child-Pugh B: (OS for CRP-elevated vs. CRP-normal, 4 vs. 15 months; P<0.001). The prognostic significance of elevated CRP was reproducible at a second CRP determination time point 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.