PIVKA-II serves as a potential biomarker that complements AFP for the diagnosis of hepatocellular carcinoma

Feng, Hui; Li, Bole; Li, Ze; Qian, Wei; Ren, Li

doi:10.1186/s12885-021-08138-3

Cited by 70 publications

(53 citation statements)

References 30 publications

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“…Patients with high serum AFP levels also had higher serum PIVKA-II. PIVKA-II is usually used in addition to AFP measurement for HCC diagnosis [ 42 ]. However, in this study, we found that there was a positive association between serum AFP and PIVKA-II levels in HCC patients.…”

Section: Discussionmentioning

confidence: 99%

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China

et al. 2022

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Background Alpha-fetoprotein (AFP) is a biomarker used in clinical management of hepatocellular carcinoma (HCC), however, approximately 40% of HCC patients do not present with elevated serum AFP levels. This study aimed to investigate the clinical and pathologic characteristics between AFP positive and negative HCC patients to allow for improved clinical management and prognostication of the disease. Methods This study observed a cohort of HCC patients from Eastern and Southern China with comparisons of the clinical and pathologic features between serum AFP positive and negative patient groups; patients with decompensated hepatic cirrhosis, those with chronic hepatitis B, and hepatitis B virus (HBV) asymptomatic carrier patients were used as controls. Data included the laboratory results, pathology diagnosis, clinical staging and scores were obtained from routine clinical diagnostic methods. Results Patients with HCC, larger tumor sizes, liver cancer with hepatic cirrhosis, portal vein thrombosis, metastasis, high Child–Pugh score, high Barcelona-Clínic Liver Cancer (BCLC) stage, and advanced clinical stage had significantly higher serum AFP levels. Also, patients with HBsAg and HBeAg positive, high HBV DNA levels had significantly higher serum AFP levels. Patients with high serum AFP levels had higher protein induced by vitamin K absence or antagonist-II (PIVKA-II), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-l-fucosidase (AFU), gamma-glutamyl transpeptidase (γ-GT), γ-GT /ALT, direct bilirubin (DBIL), indirect bilirubin (IDBIL), fibrinogen, and D-dimer levels. Patients with AFP positive had higher white blood cells (WBC), neutrophil, monocyte, and platelet count and neutrophil to lymphocyte ratio (NLR). Conclusions The are significant differences in clinical pathologic characteristics between AFP positive and negative HCC patients which may be helpful for the management and prognostication of the disease.

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Section: Discussionmentioning

confidence: 99%

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China

et al. 2022

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“…PIVKA-II is another widely used HCC marker with high specificity. PIVKA-II is a powerful supplement to AFP in HCC diagnosis [ 35 ], and their combination could improve the accuracy [ 35 – 38 ]. Recent reports have suggested that the ratio of gamma-glutamyltransferase to aspartate aminotransferase (γ-GT/AST) and the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3) are valuable markers in HCC diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Validation and update of a multivariable prediction model for the identification and management of patients at risk for hepatocellular carcinoma

Zhao

Cai

et al. 2021

Clin Proteom

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Background A hepatocellular carcinoma (HCC) prediction model (ASAP), including age, sex, and the biomarkers alpha-fetoprotein and prothrombin induced by vitamin K absence-II, showed potential clinical value in the early detection of HCC. We validated and updated the model in a real-world cohort and promoted its transferability to daily clinical practice. Methods This retrospective cohort analysis included 1012 of the 2479 eligible patients aged 35 years or older undergoing surveillance for HCC. The data were extracted from the electronic medical records. Biomarker values within the test-to-diagnosis interval were used to validate the ASAP model. Due to its unsatisfactory calibration, three logistic regression models were constructed to recalibrate and update the model. Their discrimination, calibration, and clinical utility were compared. The performance statistics of the final updated model at several risk thresholds are presented. The outcomes of 855 non-HCC patients were further assessed during a median of 10.2 months of follow-up. Statistical analyses were performed using packages in R software. Results The ASAP model had superior discriminative performance in the validation cohort [C-statistic = 0.982, (95% confidence interval 0.972–0.992)] but significantly overestimated the risk of HCC (intercept − 3.243 and slope 1.192 in the calibration plot), reducing its clinical usefulness. Recalibration-in-the-large, which exhibited performance comparable to that of the refitted model revision, led to the retention of the excellent discrimination and substantial improvements in the calibration and clinical utility, achieving a sensitivity of 100% at the median prediction probability of the absence of HCC (1.3%). The probability threshold of 1.3% and the incidence of HCC in the cohort (15.5%) were used to stratify the patients into low-, medium-, and high-risk groups. The cumulative HCC incidences in the non-HCC patients significantly differed among the risk groups (log-rank test, p-value < 0.001). The 3-month, 6-month and 18-month cumulative incidences in the low-risk group were 0.6%, 0.9% and 0.9%, respectively. Conclusions The ASAP model is an accurate tool for HCC risk estimation that requires recalibration before use in a new region because calibration varies with clinical environments. Additionally, rational risk stratification and risk-based management decision-making, e.g., 3-month follow-up recommendations for targeted individuals, helped improve HCC surveillance, which warrants assessment in larger cohorts.

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“…The well-established biomarker AFP evaluated in many studies had high proportions of false positives. The novel biomarker PIVKA-II had better diagnostic performance with higher specificity in HCC early detection despite the conditions including vitamin K deficiency, malnutrition, drug (e.g., warfarin), and obstructive jaundice ( 64 , 70 , 71 ). In addition, the mechanism of PIVKA-II and AFP was independent.…”

Section: Clinical Relevance Of Pivka-ii In Hccmentioning

confidence: 99%

Progression of Prothrombin Induced by Vitamin K Absence-II in Hepatocellular Carcinoma

Yang

et al. 2021

Front. Oncol.

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Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related death worldwide. Due to the lack of efficient tools for early detection, asymptomatic HCC patients are diagnosed at an advanced stage, leading to a poor prognosis. To improve survival, serum biomarker prothrombin induced by vitamin K absence-II (PIVKA-II) was under investigation. PIVKA-II is an abnormal protein produced in HCC. The coagulation function was insufficient due to the lack of Gla residues. Elevated PIVKA-II was associated with bad tumor behavior in terms of proliferation, metastasis, and invasion. Three major signaling pathways were proposed to clarify the mechanism. With the advantages including affordability, minimal invasiveness, convenience, and efficiency, PIVKA-II could improve HCC management consisting of four aspects. First, PIVKA-II was an effective and dynamic tool for improving HCC surveillance in high-risk population. Changes in the serum levels of PIVKA-II provided valuable molecular alteration information before imaging discovery. Second, PIVKA-II offered a complementary approach for HCC early detection. Compared to traditional diagnostic approaches, the combination of PIVKA-II and other biomarkers had better performance. Third, PIVKA-II was an indicator for the assessment of response to treatment in HCC. Preoperative assessment was for selecting personalized therapy, and postoperative measurement was for assessing treatment efficacy. Fourth, PIVKA-II was considered as a prognostic predictor for HCC. Patients with elevated PIVKA-II were more likely to develop microvascular invasion, metastasis, and recurrence.

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PIVKA-II serves as a potential biomarker that complements AFP for the diagnosis of hepatocellular carcinoma

Cited by 70 publications

References 30 publications

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China

A comparison of clinical pathologic characteristics between alpha-fetoprotein negative and positive hepatocellular carcinoma patients from Eastern and Southern China

Validation and update of a multivariable prediction model for the identification and management of patients at risk for hepatocellular carcinoma

Progression of Prothrombin Induced by Vitamin K Absence-II in Hepatocellular Carcinoma

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