Application of multiple inflammatory markers combined with PIVKA-II in differential diagnosis of AFP-NHCC

Alpha-fetoprotein (AFP) is a proven blood biomarker widely used in clinical detection of liver cancer, and its concentration increases immediately after liver injury, with high diagnostic specificity and low sensitivity. However, in patients with AFP-negative hepatocellular carcinoma (AFP-NHCC), also known as small liver cancer, their early stage of AFP expression is usually low or close to the normal range. Compared with AFP-positive HCC, AFP-NHCC is more likely to be subjected to missed diagnosis due to solely dependence on the measurement of blood AFP. Therefore, it is necessary to find a reliable, effective, and economical detection method for the early diagnosis of AFP-NHCC. PIVKA-II is closely related to the occurrence, development, invasion, and metastasis of liver cancer, and is also a new hematological marker widely used in the diagnosis of liver cancer in recent years. PIVKA-II effectively makes up for the limitation of negative AFP. 63.2% – 76.3% of patients with negative AFP showed positive PIVKA-II, and if only PIVKA-II detection was relied on, there would still be missed diagnosis in early patients with AFP-NHCC. In this retrospective study, we selected several commonly used inflammatory indicators to explore the diagnostic efficacy of PIVKA-II, an abnormal form of prothrombin, combined with inflammatory indicators in patients with early-stage AFP-NHCC and analyzed the relationship between some clinical features and hematological indicators in patients with AFP-NHCC. Serum levels of high-sensitivity C-reactive protein (hs-CRP), prealbumin (PA), neutrophil/lymphocyte ratio (NLR), and PIVKA-II were compared among three groups (AFP-NHCC group, benign lesion group, and healthy subjects). The diagnostic efficacy of PIVKA-II alone for AFP-NHCC and the diagnostic efficacy of three inflammatory indicators combined with PIVKA-II for AFP-NHCC were calculated, and their diagnostic specificity and sensitivity were compared. Compared with the other two groups, the AFP-NHCC group showed significant changes in three inflammatory markers and PIVKA-II, which may be related to the inflammatory progression of the tumor. Therefore, we recommend the establishment of a laboratory-based detection approach for diagnosing early-stage AFP-NHCC by combining PIVKA-II with inflammatory indicators hs-CRP, PA, and NLR, to facilitate diagnosis, treatment, and prognosis of AFP-NHCC.