Impact of etiology of chronic liver disease on hepatocellular carcinoma biomarkers

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.