2, 3 In the validation cohort, all patients received TACE as described.17 Several patients with HCC showed elevated CRP levels without any signs of clinically evident infection (CEI). To evaluate the prevalence of this frequently neglected clinical observation separately from CRP elevations with alternative explanations we created the variables “CRP, associated with CEI” and

PS-341 concentration “CRP, nonassociated with CEI” and compared their frequencies in our HCC cohorts was well as in 104 well-defined cirrhosis patients of the TIPS-data base of the Medical University of Vienna (Supporting Methods, Supporting Fig. 2). Patients were summarized in the variable “CRP, associated with CEI” if at least one of the conditions outlined in the Supporting Methods section was documented during the hospital admission at the time of diagnosis. Additionally, we analyzed the association of “CRP, nonassociated with CEI” and “CRP, associated with CEI” with tumor characteristics, causes of death, and their impact on overall survival (OS). In all cohorts, baseline patient characteristics were presented using descriptive statistics. To determine the optimal Tanespimycin in vivo cutoff for CRP-related analysis, we used a spline-based approach in the training cohort to assess the functional form of CRP on OS.18 Based on this graphical representation a clinically sensible

and applicable transformation of CRP was chosen. Survival curves were calculated using the Kaplan-Meier method. OS was defined as the time between the date of diagnosis (date of HCC biopsy if available or diagnostic imaging) and the date of death. Additionally, we performed confirmatory analysis at a second timepoint based on a second independent CRP determination. In these confirmatory analyses, OS was defined as

the time from the second CRP determination until death. Patients who were still alive on December 1 2011 (end of follow-up) or who were lost to follow-up were censored at the date of the last contact. Univariate analyses were performed by means of the log-rank test. Variables that reached a P-value of ≤ 0.05 in the univariate analysis were entered into a multivariate analysis. The multivariate analysis was performed using a Cox proportional Oxalosuccinic acid hazard regression model. P < 0.05 was considered significant. The prognostic performance of CRP was evaluated in an independent external validation cohort with and without stratification according to the BCLC stage and within each BCLC stage according to the Child-Pugh stage. Statistical analyses were performed using SPSS v. 19.0 (Chicago, IL) and SAS v. 9.3 (Cary, NC). A total of 466 patients met the inclusion criteria for the training cohort of this study (Fig. 1), of which 400 patients (86%) were diagnosed by radiologic imaging plus biopsy and 66 patients were diagnosed by radiologic imaging only. Patient characteristics of the training cohort are given in Table 1.