46, 47 This study undoubtedly has some limitations. In the current version of the ITA.LI.CA database, data regarding tumor recurrence after treatment are not

available, and therefore in this study the influence of alpha-fetoprotein levels on some important composite Ferroptosis phosphorylation endpoints such as recurrence plus death could not be assessed. Furthermore, as expected in our country, hepatitis virus infection was the cause of cirrhosis in most cases, and therefore it remains to be established whether these results can be generalized to HCC patients with other etiologies.48, 49 Lastly, although the ITA.LI.CA database includes more than 3,000 HCC patients, the selection http://www.selleckchem.com/products/torin-1.html criteria for this study were very strict, and therefore the study population was limited to 205 patients. A post-hoc analysis shows that this sample size had a statistical power of 22% to detect a difference between the observed 5-year survival rates of patients with alpha-fetoprotein below (61%) and above (55%) 20 ng/mL. With such survival rates, a sample size

of 2,118 patients with compensated cirrhosis and single, small HCC treated with curative intent, derived from a population of more than 30,000 patients with HCC, would have been needed to achieve a power of 80%. All in all, we feel that even these figures, if framed in the context of clinical practice, confirm the bland prognostic potential of alpha-fetoprotein in the subset of patients we selected. In conclusion, we found that serum alpha-fetoprotein has no prognostic role in compensated cirrhosis patients with a single, small HCC diagnosed during surveillance and treated with curative intent. These findings emphasize the futility of serum alpha-fetoprotein determination in a clinical setting where surveillance for HCC may provide its maximal benefit in terms of amenability to curative treatment and patients survival. New, more accurate markers are therefore needed to improve our current ability

to predict the outcome of patients diagnosed with early HCC. Other members of the ITA.LI.CA group: Dipartimento di Medicina Clinica, Alma Mater Studiorum, 上海皓元 Università di Bologna, Italy: Mauro Bernardi, Maurizio Biselli, Romina Cassini, Paolo Caraceni, Marco Domenicali, Virginia Erroi, Marta Frigerio, Annagiulia Gramenzi, Barbara Lenzi. Dipartimento di Medicina Interna, dell’Invecchiamento e Malattie Nefrologiche, Azienda Ospedaliero-Universitaria di Bologna, Italy: Donatella Magalotti. Divisione di Medicina, Azienda Ospedaliera Bolognini, Seriate, Italy: Claudia Balsamo, Maria Di Marco, Elena Vavassori. Divisione di Medicina, Ospedale Treviglio-Caravaggio, Treviglio, Italy: Lodovico Gilardoni, Mario Mattiello.