In summary, 114 patients (25%) underwent local therapy (percutaneous ethanol injection: n = 101 or radiofrequency ablation n = 13), 144 (31%) received TA(C)E (transarterial embolization: n = 32, or chemoembolization: n = 112), 133 (29%) received medical therapy (sorafenib: n = 32, somatostatin analogs: n = 53, doxorubicin: n = 7, other medical therapy: n = 41) and two patients (0.4%) received radiation therapy. Between selleck January 2001 and January 2008 252 patients were entered into the TACE database of the Medical University of Innsbruck,

of which 149 patients were eligible for the validation cohort of this study (Fig. 1). All patients were diagnosed by radiologic imaging only. Patient characteristics of the validation cohort are given in Table 1. In total, 141 patients received conventional TACE with lipiodol and doxorubicin within 10 days of HCC diagnosis. Seven patients

exceeded the maximum tolerated doxorubicin dose and were thereafter treated with TAE only. One patient received TACE with drug-eluting beads. The patients received a median number of three TACE cycles (range 1-20). Second-line therapies after TACE included best supportive care (n = 118), CHIR 99021 local-ablative intervention (radiofrequency ablation: n = 13, percutaneous ethanol injection: n = 1, radiation therapy: n = 1), and medical treatment (sorafenib: n = 7 and other therapies: n = 9). In the training cohort 367 of 466 (79%) patients died during the observational period between April 1, 1999 and December 1, 2011, while 47 (10%) subjects were still alive and 52 (11%) patients were lost to follow-up. The distributions and mean CRP levels of patients in the training and the validation cohort are given in Table 1 and Fig. 2A. Mean CRP levels slightly increased with increasing BCLC-stages (BCLC stage A/B/C/D: 0.9/ 1.8/2.7/3.6 mg/dL, P < 0.0001). We first evaluated the impact of CRP levels on patient outcomes by a regression Rebamipide spline analysis. We found a sigmoid-shaped association of CRP levels and the hazard ratio of death, and no increase

of the hazard ratio of death was observed with CRP levels beyond 2 mg/dL (Fig. 2B). Thus, we next formed four different CRP cutoffs between 0 and 2 mg/dL (A: 0-0.5; B: >0.5 and <1, C: ≥1 and ≤2, D: >2 mg/dL). No statistical or clinically meaningful survival difference was observed between the cutoffs A and B or C and D (Fig. 2C). Hence, we used the CRP cutoff <1 versus ≥1 mg/dL (hereafter designated as “normal” and “elevated” CRP) and tested this cutoff in the validation cohort (Fig. 2D). Analysis of the validation cohort confirmed the prognostic power of elevated CRP levels regarding OS in patients with HCC (OS elevated CRP versus normal CRP: 6.2 versus 20.6 months [95% confidence interval, CI: 3.8-8.7 versus 14-27.2], P < 0.0001). We tested the reproducibility of our findings by using another CRP determination at a second independent timepoint (Fig. 2E).