The role of PIVKA-II in hepatocellular carcinoma surveillance in an Asian population

Abstract

Alpha-fetoprotein (AFP) is the most established biomarker for surveillance of hepatocellular carcinoma (HCC) in at-risk individuals. However, its sensitivity and specificity are not very satisfactory. 1 Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is a newer biomarker for HCC but without a widely established cut-off. 2,3 Recent data suggested that the cut-off may be different for HCC due to chronic hepatitis C (CHC) and chronic hepatitis B (CHB) infection. 4 Two different reference intervals (RIs), Japan and European Union (EU), are provided in the assay kit (Architect PIVKA-II, Abbott Laboratories, Chicago, US). 5 In Singapore, CHB is the most prevalent association with HCC. 6 Hence, we studied the distribution of PIVKA-II to determine which RI was more applicable to our Singapore patients. We also examined for significant associations between HCC and PIVKA-II alone, AFP alone, and the combination of both PIVKA-II and AFP.Study subjects had blood drawn on the day of their 6-monthly HCC surveillance ultrasound for up to a maximum of 3 visits. PIVKA-II, AFP (Abbott Laboratories, Chicago, US) and AFP (Roche Elecsys; Roche Diagnostics, Basel, Switzerland) were assayed at the same time. Ultrasound and blood results were reviewed by a clinician. Suspicious lesions were investigated and HCC was diagnosed in accordance with international guidelines. Patient consent was obtained. SingHealth Centralised Institutional Review Board approved the study (reference CIRB 2017/2577).Six hundred and ten patients in our HCC surveillance programme, who were without HCC for the prior 12 months, were enrolled. Majority were males (60.7%). Median age was 62 years (interquartile range [IQR] 55-69). Most had CHB (89.5%), of which 59.6% were on antiviral treatment with good control of the disease in 98.8%. Baseline median levels of alanine transaminase and aspartate transaminase of the cohort were 22U/L (IQR 17.0-32.0) and 25U/L (IQR 22.0-32.0), respectively. Median follow-up was 12.2 months, with 632 patient-years. About half (54.4%) had the second and 19.2% the third visit blood specimens taken.