Determinants of alpha-fetoprotein levels in patients with hepatocellular carcinoma: Implications for its clinical use


  • Other members of the ITA.LI.CA Group: Mauro Bernardi, Luigi Bolondi, Maurizio Biselli, Paolo Caraceni, Alessandro Cucchetti, Marco Domenicali, Virginia Erroi, Rita Golfieri, Annagiulia Gramenzi, Barbara Lenzi, Donatella Magalotti, Fabio Piscaglia, Matteo Ravaioli, and Laura Venerandi (Department of Medical and Surgical Sciences, Alma Mater Studiorum-University of Bologna, Bologna); Anna Giacomin, Veronica Vanin, Caterina Pozzan, and Gemma Maddalo (Department of Surgical and Gastroenterological Sciences, University of Padua, Padua); Paolo Del Poggio and Stefano Olmi (Operative Surgical Unit, San Marco Polyclinic, Zingonia); Claudia Balsamo, Maria Anna Di Nolfo, and Elena Vavassori (Operative Medical Unit, Bolognini Teaching Hospital, Seriate); Alfredo Alberti, Luisa Benvegnù, Angelo Gatta, and Maurizio Gios (Department of Clinical and Experimental Medicine, University of Padua, Padua); Emanuela Giampalma, Rita Golfieri, Cristina Mosconi, and Matteo Renzulli (Operative Radiology Unit, Department of Digestive Tract Diseases and Internal Medicine, Teaching Hospital-University of Bologna, Bologna); Giulia Bosco (Unit of Internal Medicine and Gastroenterology, Columbus Integrated Complex, Catholic University of Rome, Rome); Paola Roselli (Operative Gastroenterology Unit, Belcolle Hospital, Viterbo); Serena Dell'Isola and Anna Maria Ialungo (Operative Unit of Preventive Medicine, Belcolle Hospital, Viterbo); Vincenzo Savarino, Antonino Picciotto, Domenico Risso, Simona Marenco, and Linda Bruzzone (Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa); Maria Chiaramonte (Gastroenterology Unit, Don Calabria Sacred Heart Hospital, Negrar); Calogero Cammà, Marcello Maida, Arezia Di Martino, and Maria Rosa Barcellona (Gastroenterology Unit, Biomedical Department of Internal and Specialty Medicine, University of Palermo, Palermo); Andrea Mega (Gastroenterology Unit, Bolzano Regional Hospital, Bolzano); Emanuele Rinninella (Unit of Internal Medicine and Gastroenterology, Gemelli Polyclinic, Catholic University of Rome, Rome); Valeria Mismas (Operative Unit for Gastroenterology and Metabolic Diseases, Teaching Hospital-University of Pisa, Pisa); Arianna Lanzi, Giuseppe Francesco Stefanini, Anna Chiara Dall'Aglio, Federica Mirici Cappa, Elga Neri, Paolo Bassi, and Miriam Zanotti (Department of Internal Medicine, Faenza Hospital for the Infirm, Faenza); Elisabetta Biasini and Emanuela Porro (Unit of Infectious Diseases and Hepatology, Teaching Hospital-University of Parma, Parma); Maria Guarino (Gastroenterology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples); and Laura Schiadà and Stefano Gemini (Gastroenterology Clinic, Marche Polytechnic University, Ancona).



α-Fetoprotein (AFP) is a biomarker commonly used in the management of patients with hepatocellular carcinoma (HCC), although the possible determinants of its serum levels in these patients have not been adequately explored. For this study, the authors evaluated the relevance of demographic, clinical, and oncologic factors to the presence of elevated AFP levels in large cohort of patients with HCC.


In 4123 patients with HCC who were managed by the Italian Liver Cancer Group, AFP levels were assessed along with their association with demographic, biochemical, clinical, and oncologic characteristics. Patients were subdivided according to the presence of elevated AFP (ie, >10 ng/mL).


AFP levels were elevated in 62.4% of patients with HCC. Multivariate logistic regression analysis indicated that being a woman (odds ratio [OR], 1.497; 95% confidence interval [95%CI], 1.250-1.793; P < .0001), the presence of cirrhosis (OR, 1.538; 95% CI, 1.050-2.254; P = .027), liver disease with viral etiology (OR, 1.900; 95% CI, 1.589-2.272; P < .0001), an elevated alanine aminotransferase level (OR, 1.878; 95% CI, 1.602-2.202; P < .0001), a low albumin level (OR, 1.301; 95% CI, 1.110-1.525; P = .012), an HCC tumor size >2 cm (OR, 1.346; 95% CI, 1.135-2.596; P = .001), multinodular HCC (OR, 1.641; 95% CI, 1.403-1.920; P < .0001), and the presence of vascular invasion (OR, 1.774; 95% CI, 1.361-2.311; P < .0001) were associated independently with elevated levels of AFP. Both the median AFP level and the proportion of patients who had elevated levels increased with decreasing degrees of HCC differentiation (P < .0001).


Sex and features of chronic liver disease were identified as nontumor characteristics that influence serum AFP levels in patients with HCC. These findings should be taken into account as limitations in interpreting the oncologic meaning of this biomarker in clinical practice. Cancer 2014;120:2150–2157. © 2014 American Cancer Society.