Background & Aims: We elaborate a non-invasive score system for liver fibrosis (NISF), exploring its diagnostic performance and comparing its accuracy to FibroScan in patients with chronic viral hepatitis (CH) and nonalcoholic fatty liver disease (NAFLD). Methods: Clinical, biochemical, elastographic and ultrasound parameters derived from patients with CH (n = 83) or NAFLD (n = 58), undergoing liver biopsy for fibrosis assessment, were prospectively collected as potential predictors of fibrosis. Each parameter was evaluated for its correlation with the liver biopsy (Gold Standard). Candidate predictors with good interobserver agreement and correlation with histological stages were combined into two algorithms (NISF) to predict fibrosis in chronic viral hepatitis and NAFLD. Results: The CH-NISF included six parameters: bluntness of liver edges, irregularity of left lobe surface, diameter of segment 4, liver stiffness measurement, platelet count and ALT values. The ability of the model to discriminate F3-F4 vs F0-F1 stages and F2 vs F0-F1 was high (AUROC of 0.95 and 0.83 respectively) and better than FibroScan alone, especially in intermediate stages (F2 vs F0-F1), AUROC 0.83 vs 0.57 (P = 0.003). The resulting algorithm is available as mathematical formula, nomogram or free online link. [http://health.mafservizi.it/NISF_Calculator/liver.htm] The NAFLD-NISF included liver stiffness, platelet count and AST levels, had good ability to discriminate F0-F1 vs F2-F3-F4 stages (AUROC 0.86), however, not significantly higher than FibroScan. Conclusions: CH-NISF can be proposed as preliminary and easily available staging tool, superior to FibroScan alone in predicting histological fibrosis, especially in intermediate stages. Further validations are needed to improve NISF accuracy in NAFLD.

BACKGROUND/AIMThe impact of radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) on survival in patients with small hepatocellular carcinoma (HCC) is unclear. We compared their efficacy in cirrhotics with single HCC ≤2 cm.PATIENTS AND METHODSTwo hundred forty-four cirrhotics with single HCC ≤2 cm treated with PEI (108 cases) or RFA (136 cases) were enrolled in the study. Eighty-one patients in each group were selected for propensity score matching analysis.RESULTSThe five-year survival was not significantly different (64.7% in PEI and 72.9% in RFA group) but the 5-year recurrence (73.3% in PEI and 49% in RFA group, p=0.023) and local tumor progression (49% in PEI and 30.1% in RFA group, p=0.018) were higher in the PEI group.CONCLUSIONPEI and RFA are equally effective in treating HCCs smaller than 2 cm in terms of 5-year survival, despite higher cumulative and local recurrence rates, in patients treated with PEI.

Introduction: Accurate and widely available methods for non-invasive assessment of liver fibrosis are increasingly needed in clinical practice.

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.12761 This article is protected by copyright. All rights reserved. Received Date : 24-Jul-2014 Revised Date : 22-Nov-2014 Accepted Date : 02-Dec-2014 Article type : Original Articles

Introduction: Sorafenib and Y90-Radioembolization (TARE) are the optional therapies for cirrhotic patients with advanced mono-lobar hepatocellular carcinoma (HCC).

Conclusions: HSC express ActRIIB and respond to myostatin with increased chemotaxis, reduced proliferation, and increased expression of profibrogenic genes

POSTERS group (range 2-189) and in the RFA group (range 6-111) (p = 0.99).No procedure related mortality was noted.Major complications occurred only in 1 patient for both treatment group (p = 0.87).OS rates at 1-, 3-, 5-years were 97%, 83.3% and 64.6% in PEI group, and 97.7%, 77.1% and 62.3%, in RFA group (p = 0.16).HCC-related death occurred in only 42.3% of PEI and 25.6% of RFA patients (p = 0.15).HCC recurrence rates at 1-, 3-, 5-years were 16.1%, 61.4%, 79.4% in the PEI group and 20.4%, 47.7%, and 57.4% in RFA group (p = 0.28).Furthermore, cumulative local tumor progression and distant intrahepatic recurrence rates were not different between the two populations.Local tumor progression was diagnosed mostly in the first 2 follow up years (77.7% in PEI group and 71.4% in RFA group).Multivariate analysis revealed that ascites was the only pretreatment risk factor negatively associated with OS in both groups (OR = 13.6,95% CI 2.5-73.3,p = 0.002 for PEI group and OR = 8.7, 95% CI 2.8-27, p < 0.001 for RFA group).Conclusions: PEI and RFA are equally effective in the treatment of HCC ≤2 cm in terms of OS, local tumor progression and overall HCC recurrence.

Levels of serum heat shock protein 27 (sHsp27) have been studied in numerous cancer types, but their potential relevance in patients with hepatocellular carcinoma (HCC) is undetermined. Our aim was to compare sHsp27 levels in patients with HCC and HCC-free controls. Specifically, we recruited 71 patients with HCC (80 % with early tumour), 80 patients with chronic liver disease (59 with liver cirrhosis and 21 with chronic active hepatitis) and 42 healthy subjects. sHsp27 was measured by immunoenzymatic assay. Results showed that sHsp27 levels were significantly (p < 0.001) higher in patients with HCC than in the other groups, particularly in those with hepatitis C virus (HCV)-related disease. In HCC patients, sHsp27 levels were not associated with prognostic risk factors, such as size/multiplicity of nodules and stage. In logistic regression analysis, performed in patients with liver disease, log-sHsp27 was associated with a significant age-adjusted 2.5-fold increased odds ratio of HCC and with a significant 4.4-fold higher odds ratio of HCC in the subgroup with HCV-related liver disease. In receiver operating characteristic curve analysis, sensitivity and specificity of the best sHsp27 cut-off value (456.5 pg/ml) for differentiating patients with HCC from those with HCC-free chronic liver disease were 70 and 73 %, respectively. In conclusion, sHsp27 levels are enhanced in patients with HCC and may represent a candidate biomarker of HCC.

Background and aims Western guidelines consider radiofrequency ablation (RF) as the standard treatment for very early' and early' hepatocellular carcinoma (HCC) in nonsurgical cirrhotic patients. RF has also been proposed as the first-line therapy for surgical' candidates with a single nodule of 20 mm or less. The aim of this monocentric cohort study was to evaluate the technical and clinical outcomes of RF in the treatment of cirrhotic patients with a single HCC of 30 mm or less.Patients and methods We included all 209 consecutive patients treated between January 2001 and June 2011. The primary endpoints were the overall survival (OS) rate and safety; the secondary endpoints were primary technique effectiveness, local tumor progression, and the disease-free survival rate.Results The 5-year OS rate of the entire sample was 44.3% (95% confidence interval: 36.7-55.8); Child-Pugh class B was the worst negative prognostic factor (hazard ratio: 2.06; P=0.008). A subgroup of 70 Child-Pugh class A patients suitable for surgical resection according to current Western operability criteria showed a 5-year OS rate of 60.6%. Treatment-related mortality and morbidity rates were 0 and 3.4%, respectively. Primary technique effectiveness rate was 95.2% after one to three RF sessions. The 5-year cumulative incidence of local tumor progression was 21.5 and 32.5% for nodules 20 and 21-30 mm, respectively. The 5-year disease-free survival rate (comprehensive of any kind of tumor progression or death) was 17.8% (95% confidence interval: 11.1-25.8).Conclusion RF is an effective and very safe therapy for HCC up to 30 mm; in surgical' cirrhotic patients, the OS rate was similar to those reported in surgical series, although the local recurrence rate was higher. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Background & Aims: The aim of this study was to compare liver resection and radiofrequency ablation in patients with single hepatocellular carcinoma <= 3 cm and compensated cirrhosis.Methods: The study involved 544 Child-Pugh A cirrhotic patients (246 in the resection group and 298 in the radiofrequency group) observed in 15 Italian centers. Overall survival and tumor recurrence rates were analyzed using the Kaplan Meier method before and after propensity score matching. Cox regression models were used to identify factors associated with overall survival and tumor recurrence.Results: Two cases of perioperative mortality were observed in the resection group and the rate of major complications was 4.5% in the resection group and 2.0% in the radiofrequency group (p = 0.101). Four-year overall survival rates were 74.4% in the resection group and 66.2% in the radiofrequency group (p = 0.353). Four-year cumulative HCC recurrence rates were 56% in the resection group and 57.1% in the radiofrequency group (p = 0.765). Local tumor progression was detected in 20.5% of ablated patients and in one resected patient (p <0.001). After propensity score matching, both survival and tumor recurrence were still not significantly different although a trend towards lower recurrence was observed in resected patients. Older age and higher alpha-fetoprotein levels were independent predictors of poor overall survival while older age and higher alanine-aminotransferase levels resulted to be independent factors associated with higher recurrence rate.Conclusions: In spite of a higher rate of local tumor progression, radiofrequency ablation can provide results comparable to liver resection in the treatment of single hepatocellular carcinoma <= 3 cm occurring in compensated cirrhosis. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Background and Aims: Sporadic data suggest HCC outcome is improving over time.We compared two independent cohorts of patients recruited on field at 10 years distance each with the aim of assessing if changes occurred on: epidemiologic, etiologic and clinical characteristics; characteristics of HCC at presentation and outcome. Methods:The study was performed in two Italian multicentre cohorts of consecutive new HCCs in cirrhosis detected in two time periods: cohort 1 (C1) included 327 patients (Jan-Dec 1998) and cohort 2 (C2) 718 patients (Sept 2008-Dec 2011).HCC was diagnosed according to the current criteria at that period and HCC managed accordingly.Patients of both cohorts were stratified according to Child-Pugh and MELD score.HCC was staged according to TNM classification and BCLC system.Each centre was free in clinical decisions.Results: C1 patients were significantly older and non-viral-nonalcoholic cirrhosis doubled in C2.At presentation, in C2 liver function was better and comorbidities were more frequent.In both cohorts BCLC very early/early stages were prevalent being significantly higher in C2.BCLC stage B and C were equally distributed, while patients in BCLC stage D were significantly more frequent in C1.In C2 HCCs were more frequently detected under regular US surveillance and were significantly smaller and uni/paucinodular.As a whole treatment, no matter which, was more frequently offered to C2 patients (76.5% vs 52.3%; p < 0.001) and in C2 significantly increased the rate of patients treated by TACE.Ablation was more frequently employed in C2 (p = 0.07).PEI ablation significantly decreased across C1 and C2 while RF became the prevalent ablative method in C2.Median survival was significantly higher in C2 (25.3 vs 18.4 mos; p < 0.05).Cumulative C1 and C2 survival at 1 and 3 years was 65% and 22% and 67% and 37%.HCC size (<3 cm), BCLC stage A and to be treated independently predicted survival.Conclusions: This study confirmed that HCC outcome improved over time mainly because: better profile of cirrhosis; better profile of HCC at presentation; increasing rate of treated cases.These data should encourage further efforts to implement HCC approach in every day clinical practice.

Background: Radiofrequency Ablation is the most widely performed percutaneous treatment for Hepatocellular Carcinoma. This multicentre study was aimed at assessing the complication, overall survival and disease-free survival rates in cirrhotic patients with single Hepatocellular Carcinoma nodule <= 3 cm undergoing Radiofrequency Ablation.Methods: Data of 365 patients (59% males; mean age 67 +/- 8 years), Child-Pugh A/B, with single Hepatocellular Carcinoma nodule <= 3 cm (tumours >2-3 cm = 127/236), showing complete necrosis after Radiofrequency Ablation between 1998 and 2010 in 7 Italian Centers were retrospectively reviewed. Complication, overall survival and disease-free survival rates were analyzed as main clinical end-points.Results: Major complications were observed in 8 patients (2.2%) and minor complications in 23 patients (6.3%). The 3-, and 5-year overall survival rates were 80% and 64%. One hundred and seven patients (29.5%) died, being 41 deaths (38.3%) Hepatocellular Carcinoma-related. At multivariate analysis only age (p = 0.04; OR 2.29), ascites (p < 0.001; OR 3.74) and Child-Pugh class >= B8 (p = 0.003; OR 2.42) were confirmed as independent predictors for overall survival. The disease-free survival rates at 3- and 5-year were 50%, and 41.8%.Conclusions: Radiofrequency Ablation is an effective and safe tool for the treatment of single Hepatocellular Carcinoma <= 3 cm providing excellent 5-year overall survival and disease-free survival rates. Patient's age and liver status appeared as main determinants of outcome. (C) 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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 %.

Background Microwaves (MW) technology is an ablative treatment alternative to radiofrequency (RF) for early stages of hepatocellular carcinoma (HCC) in cirrhotic patients not suitable for surgical resection. It is well known that HCC lesions ≥ 30 mm treated by RF show a high rate of local tumor progression because of residual of unablated neoplastic tissue. Methods Aim of this study was to describe a limited experience of MW ablation (9 cirrhotic patients with medium size HCC: 11 lesions, 31 - 50 mm in diameter) treated from June 2009 to May 2010 by one of currently marketed western MW ablation systems and followed up for 2 years. Primary end-point was the probability of local tumor progression at 24 months; secondary end-point was the safety of the procedure. Results Radiological response after a single session and re-evaluation of local tumor progression along the time were performed by contrast enhanced computed-tomography at months 1-8-12-24. Early effectiveness rate was 90.1 %. The cumulative incidence of local tumor progression at 1 and 2 years were 36.4% (95% CI 11.2 - 62.7) and 57.6% (95% CI 23.6 - 81.0). We observed a single minor complication of the procedure. Conclusions In conclusion, MW ablation system “Amica” has a high rate of primary effectiveness rate but residual of unablated neoplastic tissue induce local tumor progression in about half of the cases during the following 2 years.

upon diagnosis; however they were less likely to receive curative treatment, which largely attributed to psychosocial and behavioral limitations.As only a small percentage of patients in either group was eligible for curative treatment at diagnosis and majority of HCC diagnosis was made on incidental or diagnostic imaging, a stronger emphasis on HCC surveillance is needed.