Serum PIVKA-II: Reference Interval of Healthy Population and Establishment of Its Cutoff Value for Hepatocellular Carcinoma Diagnosis in Pakistan

Background and Objective: PIVKA-II (Protein induced by vitamin K absence II) is an upcoming and promising new biological marker cited as having a definitive role in the early detection and diagnosis of hepatocellular carcinoma (HCC). Preliminary research shows PIVKA-II reference intervals (RIs) in serum to have substantial racial disparities globally.  Hence, this study aimed to determine the RIs and cut-off value of the serum PIVKA-II for the first time in healthy and patients with hepatocellular carcinoma in Pakistan.   Methods: This cross-sectional study comprised of 240 participants (120 diagnosed cases of HCC and 120 healthy individuals) registered at the Department of Chemical Pathology and Immunology, Chughtai Institute of Pathology, Lahore, Pakistan. The PIVKA-II serum level was analyzed using the Chemistry Analyzer through chemiluminescent micro-particle immunoassay (CMIA). The reference interval was subsequently established using the percentile method.   Results: In healthy Pakistani adults, the 95 percent reference interval for PIVKA-II was 15.55-43.03mAU/ml, and the cut-off was 148.81mAU/ml in HCC (hepatocellular carcinoma) cases. The male participants, exhibited higher PIVKA-II levels than the females (P < 0.002). There were no significant differences in the serum levels of  PIVKA-II with respect to age however variations were observed with respect to gender. Conclusions: Determination of the reference interval for serum PIVKA-II in healthy adult Pakistani individuals and a cut-off for HCC diagnosis emphasizes the growing need to establish and verify reference intervals of analytes at a larger scale in our population. Ideally all clinical laboratories should establish their own reference intervals.