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Aberrant Squamous Cell Carcinoma Antigen (SCCA) expression is an early hepatocarcinogenetic event and circulating SCCA-IgM complexes are elevated in most HCC patients. We evaluated whether serum SCCA-IgM levels can identify HCV +ve cirrhotic patients at low HCC risk. In this retrospective study we enrolled 29 cirrhotic patients in whom serum SCCA-IgM was measured 8 - 69 months (median 31) before HCC diagnosis, and 28 cirrhotic patients who remained HCC- free, with SCCA-IgM measured 15 - 68 months (median 48) before the study end. The best discriminating value of SCCA-IgM was calculated and tested in predicting HCC diagnosis within 12, 24 and 36 months. Sensitivity analysis, considering different HCC incidence, was conducted to identify the patient subgroup with an annual cancer risk below the threshold of a cost-effective semiannual surveillance with ultrasound. Cumulative HCC incidence at 12, 24 and 36 months was 7.0%, 15.7% and 26.3%, respectively. SCCA-IgM levels were higher in HCC than in cirrhotic patients [median: 381 (95% C.I.: 50 - 5289) vs. 100 (70 - 493) AU/mL, P = 0.005]. The SCCA-IgM value ≤ 200 AU/mL accurately identified patients at low risk of HCC development in the subsequent year (sensitivity 75%, specificity 62%, positive predictive value 13% and negative predictive value 97%). Considering an annual HCC incidence ≤ 3%, patients with SCCA-IgM ≤ 200 AU/mL (60% of the whole patients) had an HCC risk below the accepted threshold of a cost-effective surveillance (1.5%). In conclusion, provided that our provocative results are confirmed in larger studies, SCCA-IgM serum measurement could permit implementation of a two step (with different costs) surveillance: an initial serological surveillance, based on the annual monitoring of this biomarker, and the conventional surveillance by semiannual US when SCCA-IgM becomes >200 AU/mL. This could improve the cost/effectiveness of surveillance of HCV infected patients at risk of HCC.

Background The strategy of salvage transplantation for patients with hepatocellular carcinoma is based on the premise that tumour recurrence will be still transplantable at the time of recurrence. However, patients can not only present non-transplantable recurrence but can also be over the age limit accepted for transplantation. Aims To measure the risk of being too old for salvage transplantation of patients resected for hepatocellular carcinoma within Milan criteria. Methods A Markov simulation model was developed on the basis of published literature. Results The risk of being too old for salvage transplantation depends on the time-span between age at hepatic resection and age limit, and the expected median waiting-time. Patients resected at an age 2 or 3 years below the age limit carry a risk of being too old that overcomes the probability of receiving transplantation. Salvage strategy can cause harm that depends on the tumour characteristics and degree of portal hypertension, becoming maximal for patients with multiple tumours, clinical signs of portal hypertension and increased bilirubin levels. Conclusions The best strategy to adopt should be balanced between the risk of being too old and the expected transplant benefit, but salvage strategy could be pursued if it did not turn into significant harm in comparison to primary transplantation.

Screening for primary liver cancer means surveillance for hepatocellular carcinoma (HCC), which is one of the most common cancers worldwide. Detection of HCC for curative treatment is increased by surveillance, but target population, optimal periodicity and cost-effectiveness aspects are still debated issues. The aim of surveillance is to obtain a reduction in HCC-related mortality and this is usually achieved through an early diagnosis that increases both applicability and cost-effectiveness of curative treatments. The aim of the present review is to analyse economic aspects of HCC surveillance. Articles that assessed cost-effectiveness of surveillance for HCC, published between 1996 and February 2013, were reviewed in order to verify the cost-effectiveness of surveillance, its optimal periodicity, the target population and the role of alternative surveillance strategies. International guidelines are currently based on the results of such cost-effectiveness analyses, highlighting the importance of the release of cost-effectiveness-guided guidelines for HCC management.

Background: The role of clinically significant portal hypertension on the prognosis of cirrhotic patients undergoing hepatic resection for hepatocellular carcinoma (HCC) is debated. Aims: In this study, our aim was to assess the role of clinically significant portal hypertension after hepatic resection for HCC in patients with cirrhosis. Methods: We assessed the prognostic role of the presence of clinically significant portal hypertension (oesophageal/gastric varices/portal hypertensive gastropathy or a platelet count 100 vs 86 months, P = 0.742). Conclusions: Presence of clinically significant portal hypertension has no influence on survival of patients with well-compensated cirrhosis undergoing hepatic resection for HCC. © 2013 John Wiley & Sons A/S.

Background Although the number of human immunodeficiency virus-infected patients with chronic liver disease is increasing, the impact of human immunodeficiency virus on hepatocellular carcinoma outcome remains unclear. Aims This single centre study investigated whether human immunodeficiency virus infection per se affects the hepatocellular carcinoma prognosis. Methods Forty-eight human immunodeficiency virus-infected and 234 uninfected patients consecutively diagnosed with hepatitis virus-related hepatocellular carcinoma from January 2000 to December 2009 were retrospectively enrolled. Hepatocellular carcinoma was staged according to Cancer of the Liver Italian Program criteria. Survival and independent prognostic predictors were evaluated. Survivals were also compared after adjustment and matching by propensity score. Results Compared to human immunodeficiency virus-uninfected subjects, infected patients were more likely to be males, were younger, had fewer comorbidities and the tumour was more often detected during surveillance. Liver function, tumour characteristics and treatments did not significantly differ between the two groups. Nevertheless, median survival of human immunodeficiency virus-infected patients was approximately half that of their counterpart (16 months [95% confidence interval: 7–25] vs. 30 months [95% confidence interval: 25–35]; p = 0.0354). Human immunodeficiency virus infection, Cancer of the Liver Italian Program score and hepatocellular carcinoma treatment were independently associated with mortality. Notably, human immunodeficiency virus infection doubled the risk of dying. These results were confirmed by propensity analysis. Conclusion Human immunodeficiency virus infection per se worsens the prognosis of patients with virus-related hepatocellular carcinoma.

The evaluated article assesses the effectiveness in clinical practice of surveillance with ultrasound (US) and α-fetoprotein (AFP) in patients at risk of developing hepatocellular carcinoma. After a median follow-up of 3.5 years, among the 442 enrolled patients with cirrhosis, 41 developed tumor (annual incidence, 2.8%). Twenty-three hepatocellular carcinomas were diagnosed at Barcelona Clinic Liver Cancer early stage (single tumor 20 ng/ml. Specificity was 91.5% for US and 90.5% for AFP. The combination of the tests increased the sensitivity to 90.2%, with a small decrease in specificity (83.3%). In a real-world setting, the combination of US and AFP would be the most effective for hepatocellular carcinoma surveillance.

Surveillance for hepatocellular carcinoma (HCC) is considered a standard of care for patients with chronic liver disease who are at risk of developing this malignancy. Several studies have shown that surveillance can improve the prognosis of patients diagnosed with HCC through an increased likelihood of application of curative or effective treatments. Repetition of liver ultrasonography (US) every 6 mo is the recommended surveillance program to detect early HCCs, and a positive US has to entrain a well-defined recall policy based on contrast-enhanced, dynamic radiological imaging or biopsy for the diagnosis of HCC. Although HCC fulfills the accepted criteria regarding cost-effective cancer screening and surveillance, the implementation of surveillance in clinical practice is defective and this has a negative impact on the cost-effectiveness of the procedure. Education of both physicians and patients is of paramount importance in order to improve the surveillance application and its benefits in patients at risk of HCC. The promotion of specific educational programs for practitioners, clinicians and patients is instrumental in order to expand the correct use of surveillance in clinical practice and eventually improve HCC prognosis.

Background Lactate dehydrogenase (LDH) is a predictor of clinical outcome in hepatocellular carcinoma (HCC) patients. However, its predictive role in the clinical outcomes of sorafenib treatment has been poorly documented. The correlation between LDH levels and clinical outcomes in HCC patients treated with sorafenib and included in the nationwide Italian database ITA.LI.CA was investigated here. Patients and Methods The ITA.LI.CA database contains data for 5,136 HCC patients. All patients treated with sorafenib treatment and with available LDH values were considered. Overall survival (OS) and time to progression (TTP) were compared in patients with LDH levels above and below a defined threshold, determined through an ROC analysis. An explorative analysis investigated the relationship between the variation of LDH levels during treatment and response to sorafenib. Results Baseline LDH levels were available for 97 patients. The most accurate cutoff value for LDH concentration was 297 U/L. Patients with LDH values above (n=45) and below (n=52) this threshold showed equal OS (12.0 months) and TTP (4.0 months) values. Data on LDH levels during sorafenib treatment were reported for 10 patients. LDH values decreased in 3 patients (mean difference = -219 U/L) who also reported a prolonged OS and TTP versus those with unmodified/increased LDH (OS: NE (not evaluated) vs. 8.0 months, p=0.0083; TTP: 19.0 vs. 3.0 months, p=0.008). Conclusions The clinical benefits of sorafenib do not seem to be influenced by baseline LDH. According to the results of an explorative analysis, however, a decreased LDH concentration during sorafenib might be associated with improved clinical outcomes.

Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Background & Aims: Lead-time is the time by which diagnosis is anticipated by screening/surveillance with respect to the symptomatic detection of a disease. Any screening program, including surveillance for hepatocellular carcinoma (HCC), is subject to lead-time bias. Data regarding lead-time for HCC are lacking. Aims of the present study were to calculate lead-time and to assess its impact on the benefit obtainable from the surveillance of cirrhotic patients. Methods: One-thousand three-hundred and eighty Child–Pugh class A/B patients from the ITA.LI.CA database, in whom HCC was detected during semiannual surveillance (n = 850), annual surveillance (n = 234) or when patients came when symptomatic (n = 296), were selected. Lead-time was estimated by means of appropriate formulas and Monte Carlo simulation, including 1000 patients for each arm. Results: The 5-year overall survival after HCC diagnosis was 32.7% in semiannually surveilled patients, 25.2% in annually surveilled patients, and 12.2% in symptomatic patients (p