Impact of etiology of chronic liver disease on hepatocellular carcinoma biomarkers

Article type: Research Article

Authors: Ricco, Gabriele^{a; g} | Cavallone, Daniela^a | Cosma, Chiara^b | Caviglia, Gian Paolo^c | Oliveri, Filippo^a | Biasiolo, Alessandra^b | Abate, Maria Lorena^c | Plebani, Mario^b | Smedile, Antonina^c | Bonino, Ferruccio^{d; e; f} | Pontisso, Patrizia^b | Brunetto, Maurizia Rossana^{a; g; *}

Affiliations: [a] Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, Reference Centre of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa, 56124 Pisa, Italy | [b] Department of Medicine, University of Padua, 35121 Padua, Italy | [c] Department of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, 10126 Turin, Italy | [d] Institute of Biostructure and Bioimaging, National Research Council, 80145 Naples, Italy | [e] University of Pittsburgh Medical Center (UPMC) Institute for Health, 53042 Chianciano Terme, Siena, Italy | [f] Fondazione Italiana Fegato, Science Park Campus Basovizza, 34149 Trieste, Italy | [g] Internal Medicine, Department of Clinical and Experimental Medicine, University of Pisa, 56127 Pisa, Italy

Correspondence: [*] Corresponding author: Maurizia Rossana Brunetto, Hepatology Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses, University Hospital of Pisa, Via Paradisa 2, 56124 Pisa, Italy. Tel.: +39 050 996857; Fax: +39 050 995457; E-mail: [email protected].

Abstract: BACKGROUND: The role of serum biomarkers in the surveillance of hepatocellular carcinoma (HCC) is controversial. OBJECTIVE: We assessed the diagnostic performances of alpha-fetoprotein (AFP) and protein-induced by vitamin-K-absence/antagonist-II (PIVKA-II) in 388 cirrhotic patients with chronic liver disease (CLD). METHODS: Biomarkers were quantified by automated chemiluminescent-enzyme-immunoassays (Fujirebio, Tokyo, Japan) at HCC diagnosis in 258 patients (204 males; median age 66.9 years) and in 130 cirrhotics without HCC (104 males; median-age 60.6 years). CLD etiology in HCC/non-HCC was CHB in 48/35, CHC in 126/56 and Non-Viral in 84/39. RESULTS: Overall AUROC values for AFP and PIVKA-II were 0.698 (95%CI = 0.642–0.753, P< 0.001) and 0.780 (95%CI = 0.730–0.831, P< 0.001). AFP/PIVKA-II AUROC (95%CI) were: 0.822 (0.728–0.915)/0.833 (0.739–0.926) in CHB, 0.648 (0.560–0.736)/0.732 (0.650–0.814) in CHC; 0.640 (0.540–0.740)/0.806 (0.722–0.889) in Non-Viral-CLD. AFP/PIVKA-II diagnostic accuracy was 40.5–59.8%/62.7–73.5% and combining both markers 78.2% for CHB, 77% for Non-Viral-CLD and 75% for CHC. AFP correlated with ALT in HCC patients with CHC (ρ= 0.463/P< 0.001) and Non-Viral CLD (ρ= 0.359/P= 0.047), but not in CHB (treated with antivirals). PIVKA-II correlated with tumour size independently of CLD-etiology (P< 0.001) and AFP in CHB patients only (P= 0.007). CONCLUSION: The diagnostic performance of AFP and PIVKA-II is significantly influenced by the etiology and activity of CLD; their combination provides a better diagnostic accuracy.

Keywords: Alpha-fetoprotein, protein induced by vitamin K absence/antagonist-II, HCC, chronic liver disease

DOI: 10.3233/CBM-170551

Journal: Cancer Biomarkers, vol. 21, no. 3, pp. 603-612, 2018