8 Tumor size (maximum diameter, expressed in cm) was assessed on imaging. When available, in patients in whom the diagnosis of HCC was histologically confirmed by fine-needle aspiration biopsy, surgical specimen, or explanted liver, the tumor was graded according to the Edmondson and Steiner classification.20 For consistency, we grouped grades I and II (well and moderately

AZD2281 differentiated) and grades III and IV (poorly differentiated) tumors.21 This study included patients who were treated with curative intent alone, considering curative the surgical (orthotopic liver transplantation, hepatic resection) and percutaneous ablative (percutaneous ethanol injection [PEI] or radiofrequency thermal ablation [RFTA]) techniques. Alpha-fetoprotein

was determined at the time of HCC diagnosis. Alpha-fetoprotein levels were classified as normal (≤20 ng/mL), mildly elevated (21-200 ng/mL), and markedly elevated (>200 ng/mL). Overall survival was calculated from the time of HCC diagnosis to death or to December 2008. Patients lost to follow-up (n = 22, 10.7%) were censored at the time of the last clinical examination. Continuous data are expressed as median value and range, see more and discrete variables as absolute and relative frequencies. To compare continuous variables we applied the Mann-Whitney U test and the Kruskal-Wallis test, whereas discrete variables were compared with the χ2 test with Yates’ correction and Fisher’s exact test, as appropriate. Patient survival was assessed according to the Kaplan-Meier method and compared by the log-rank test. A receiver operating characteristic (ROC) curve was used to identify the alpha-fetoprotein value with the highest accuracy for discriminating between survivors and deceased patients. Moreover, the ROC curve was used to identify the cutoff prevalence-adjusted positive and negative predictive values, and positive and negative likelihood ratios for death. A 2-tailed P-value < 0.05 was considered statistically significant. Statistical analysis was performed using MedCalc statistical package (MedCalc Software, Mariakerke, Belgium). The

ITA.LI.CA database management conforms to the past and current Italian legislation on the privacy and the present study conforms to the ethical guidelines of the Declaration of Helsinki. Approval for the study was obtained by the Institutional Review Board of the participating centers. Rutecarpine The main demographic, biochemical, and clinical characteristics of the 205 study patients are reported in Table 1. The main cause of liver cirrhosis was chronic infection with hepatitis viruses (n = 180, 87.8%). The Child-Pugh score was 5 in 151 patients (73.7%), and the maximum diameter of the HCC nodule was ≤2 cm in 122 patients (59.5%). Serum alpha-fetoprotein levels were within the normal range (≤20 ng/mL) in 116 patients (56.6%), mildly elevated (21-200 ng/mL) in 71 patients (34.6%), and markedly elevated (>200 ng/mL) in 18 patients (8.8%).