If liver transplantation is not feasible, partial resection is considered the treatment of choice for hepatocellular carcinoma (HCC) in patients with cirrhosis. However, in some centers the firstline treatment for small, single, operable HCC is now radiofrequency ablation (RFA). In the current study, 218 patients with single HCC < 2.0 cm (very early or T1 stage) underwent RFA. We assessed 2 primary end points that could be easily compared with those reported for resective surgery: (1) the rate of sustained, local, complete response and (2) the rate of treatment-related complications. The secondary end point was 5-year survival in the 100 patients whose tumors had been considered potentially operable. After a median follow-up of 31 months, sustained complete response was observed in 216 patients (97.2%). In the remaining 6, percutaneous ethanol injection, selective intraarterial chemoembolization, or resection were used as salvage therapy. Perioperative mortality, major complication, and 5-year survival rates were 0%, 1.8%, and 68.5%, respectively. Conclusion: Compared with resection, RFA is less invasive and associated with lower complication rate and lower costs. RFA is also just as effective for ensuring local control of stage T1 HCC, and it is associated with similar survival rates (as recently demonstrated by 2 randomized trials). These data indicate that RFA can be considered the treatment of choice for patients with single HCC < 2.0 cm, even when surgical resection is possible. Other approaches can be used as salvage therapy for the few cases in which RFA is unsuccessful or unfeasible. ( on the oncological assumption that resection is the more suitable option for obtaining the complete tumor ablation including a layer of tissue surrounding it. 2,3 The importance of the local complete response (in other words, the absence of residual neoplastic tissue at the site of the tumor) on the overall survival in patients with HCC had been proved not only for surgery but also for percutaneous ablation therapies (PATs). 4,5 PATs were originally reserved for HCCs that were, for one reason or another, unsuitable for resective surgery, but they are now proving their worth in small operable cases as well. 6,7 Radiofrequency ablation (RFA) is currently considered the most effective PAT, [8][9][10][11] and 2 recent randomized trials failed to reveal significant differences between the survival rates associated with resective surgery and RFA in patients with early HCC. 12,13 These considerations have led some centers to adopt RFA as first-line treatment for single HCC nodules less than 3.0 cm in diameter, [14][15][16][17] opening the debate over the best therapeutic option for these small tumors.To clarify this issue, we conducted a multicenter study that included a consecutive series of patients with single HCC 2.0 cm or less in diameter accompanying cirrhosis

This study demonstrates that G-CSF can be safely administrated up to four times over a 1-year period in decompensated cirrhotic patients. The repeated BMC mobilization favors the circulation of stem cells coexpressing hepatic markers and mRNA of liver-related genes.

International guidelines recommend the use of ultrasound as a surveillance tool for hepatocellular carcinoma (HCC) in patients with cirrhosis, while the role of serum biomarkers is still debated. We investigated serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA-II) and glypican-3 (GPC-3) diagnostic accuracy for HCC detection and prediction in patients with liver cirrhosis of viral etiology under surveillance. A total of 349 patients (200 cirrhosis and 149 HCC) were enrolled. The 200 patients with cirrhosis consisted of 114 patients still HCC-free after 36 months of follow-up and 86 patients that developed HCC after 13.8 (11.0–19.8) months. AFP, PIVKA-II and GPC-3 were measured in serum samples collected at tumor diagnosis in the 149 patients with HCC, and at the beginning of follow-up in the 200 patients with cirrhosis. The higher performance for HCC detection was observed for PIVKA-II (area under the curve (AUC) = 0.790), followed by AFP (AUC = 0.737) and GPC-3 (AUC = 0.637); the combination of AFP + PIVKA-II improved the diagnostic accuracy to AUC = 0.822. Serum PIVKA-II values, but not AFP and GPC-3, were significantly higher in the 86 cirrhotics that developed HCC compared with the 114 cirrhotics still HCC-free after 36 months of follow-up (p = 0.020). PIVKA-II ≥ 55 mAU/mL allowed to identify patients with cirrhosis at higher risk of HCC development (Log-rank test, p < 0.001; adjusted Hazard Ratio = 1.99, p = 0.001). In conclusion, the measurement of PIVKA-II in patients with cirrhosis may be useful to tailor personalized surveillance strategies.

Current surveillance strategy for patients with nonalcoholic fatty liver disease (NAFLD) at risk of hepatocellular carcinoma (HCC) development is unsatisfactory. We aimed to investigate the diagnostic accuracy of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), glypican-3 (GPC-3), adiponectin, leptin and interleukin-6 (IL-6), alone or in combination, for the discrimination between NAFLD patients with or without HCC. The biomarkers were investigated in a cohort of 191 NAFLD patients (median age 62, 54–68 years; 121 males and 70 females) with advanced fibrosis/cirrhosis, 72 of whom had a diagnosis of HCC. PIVKA-II showed the best performance for the detection of HCC with an area under the curve (AUC) of 0.853, followed by adiponectin (AUC = 0.770), AFP (AUC = 0.763), GPC-3 (AUC = 0.759) and by IL-6 (AUC = 0.731), while the leptin values were not different between patients with and without HCC. The accuracy of the biomarkers’ combination was assessed by a stratified cross-validation approach. The combination of age, gender, PIVKA-II, GPC-3 and adiponectin further improved the diagnostic accuracy (AUC = 0.948); the model correctly identified the 87% of the patients. In conclusion, we developed a model with excellent accuracy for the detection of HCC that may be useful to improve the surveillance of NAFLD patients at risk of tumor development.

Sorafenib is an oral multikinase inhibitor approved for the treatment of hepatocellular carcinoma (HCC). In two randomized trials, sorafenib was reported to be safe without a significant impact on quality of life (QoL). The aim of this study was to evaluate the occurrence of adverse events, QoL variations, and treatment discontinuations in HCC patients treated with sorafenib. Between November 2009 and March 2011, all patients evaluated as suitable for sorafenib treatment were enrolled. Every patient was invited to complete the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire before starting therapy, at week 1, and at months 1 and 2. QoL scores were analyzed by the Wilcoxon matched-pairs test. Side effects were classified according to the Common Terminology Criteria for Adverse Events v.3.0. Thirty-six patients were enrolled. The cumulative incidence of therapy discontinuation for drug-related adverse events was 33 % (95 % confidence interval, 20.2-49.7). The most common adverse event was fatigue (66.7 %). The worst score decrease was detected from baseline to week 1 in physical well-being, with a median reduction of -8.3 (range -60.1 to 17.9; P = 0.0003). Treatment withdrawal from adverse events was higher than previously reported, significant QoL decrease occurred, and estimated feasibility was 66.7 %.