9-52.7) after the first CRP determination. Elevated CRP levels remained associated with poor OS (median OS for elevated-CRP versus normal CRP: 9.7 versus 21.8 months; 95% CI: 5.9-13.6 versus 14.2-29.2, P = 0.001, Fig. 2E).

Finally, we analyzed the impact of CRP changes (CRP normalization or new elevation) and CRP persistence (persistently normal or persistently elevated) between the first and second CRP determination on overall survival. Only 15% of patients experienced selleck compound a CRP normalization or new CRP elevation. Persistence of CRP levels (elevated or normal) retained prognostic significance, while a new elevation of CRP was associated with a dismal prognosis (Supporting Table 1). The median overall survival

of the whole patient population (N = 466) was 11 months (95% CI, 9.1-12.9). Besides CRP, age, the BCLC classification, and its constituent factors (Child-Pugh classification, ECOG performance status, macrovascular invasion and extrahepatic spread, tumor size, and tumor number), also elevated AFP (≥400 kU/L) and AST levels (≥100 U/L) as well as treatment allocation were significantly associated see more with OS (Table 2). Upon multivariate analysis, elevated CRP levels remained a highly significant predictor for overall survival (hazard ratio [95% CI], 1.7 [1.2-2.5], P < 0.001), which was independent from age, liver function, tumor characteristics, and treatment allocation (Table 3). In the validation cohort, 上海皓元医药股份有限公司 130 patients (87%) died during the observational period between January 2001 and December 2011,

while eight subjects were still alive and 11 were lost to follow-up. The OS of the whole population (n = 149) was 15.9 months (95% CI: 12.5-19.3). The same clinical factors as in the training cohort were significantly associated with OS, with the exception of age, AFP >400 mg/dL, AST >100 U/L, and extrahepatic spread, probably due to the smaller sample size (Supporting Table 2). Strikingly, elevated CRP levels were significantly and independently associated with poor OS upon multivariate analysis (hazard ratio [95% CI], 2.0 [1.3-3.0], P < 0.001) (Supporting Table 3). Given the independent prognostic significance of elevated CRP levels in the training and the validation cohort, we evaluated the discriminative power of elevated CRP levels within the BCLC staging system. The small number of patients with elevated CRP levels in BCLC-stage A (training cohort: CRP-elevated: n = 8, validation cohort: CRP-elevated: n = 5) precluded a reasonable survival analysis in this patient group. CRP levels also had no predictive role in endstage BCLC-D patients (data not shown). In the training cohort, patients with BCLC stage B (n = 90), CRP levels-elevated (n = 29) were significantly associated with a shorter OS (median OS [95% CI] for CRP-elevated [n = 29] versus CRP-normal [n = 61]: 15 [5.1-24.9] versus 24 [17.9-30.