Prognostic value of PIVKA-II in hepatocellular carcinoma patients receiving curative ablation: A systematic review and meta-analysis

Zhang, Dongjing; Liu, Zhihong; Yin, Xueru; Qi, Xiaolong; Lu, Bingyun; Liu, Yuanyuan; Hou, Jinlin

doi:10.1177/1724600818760234

Cited by 13 publications

(21 citation statements)

References 37 publications

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“…and between AFP and PIVKA-II. It is known that a high value of AFP or PIVKA-II is a poor prognosis marker of HCC (30,31). Our study showed that high levels of FL-GPC3 were strongly related to HCC recurrence, and this might also reflect poor prognosis.…”

Section: Discussionsupporting

confidence: 48%

Usefulness of plasma full‑length glypican‑3 as a predictive marker of hepatocellular carcinoma recurrence after radial surgery

Miura

Fujinami²,

Shimizu³

et al. 2020

Oncol Lett

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Predicting the risk of hepatocellular carcinoma (HCC) recurrence before treatment is necessary for developing subsequent treatment policies. Several tumor markers found in blood, such as alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), are presently used to determine the occurrence and recurrence of HCC and to predict patient prognosis. However, these markers are insufficient for these purposes as certain patients have HCC recurrence despite exhibiting negative AFP and PIVKA-II. The present study identified glypican-3 (GPC3), an embryonal carcinoma antigen that is expressed specifically in HCC and is secreted into blood. Although the N-terminal domain of GPC3 in sera may be a potential prognostic factor for HCC, its biological role remains unclear. By contrast, full-length GPC3 (FL-GPC3) is reported to serve important roles in cell differentiation, proliferation and signaling events that cause HCC. Given the biological roles of FL-GPC3 in HCC progression, the present study evaluated its potential as a predictive marker of HCC recurrence. In the present study, a novel measurement system was constructed to specifically measure plasma FL-GPC3. Subsequently, its ability to predict recurrence after radical surgery in 39 HCC patients was evaluated. The results revealed that preoperative FL-GPC3 levels in patients with recurrence were significantly higher than those in patients without recurrence, suggesting that FL-GPC3 could be a better predictive maker of risk of recurrence than AFP or PIVKA-II. Furthermore, it was determined that the combination of FL-GPC3, AFP and PIVKA-II could predict recurrence within one year of radical surgery with high sensitivity and specificity. Based on these results, the validation of FL-GPC3 as a predictive marker of HCC recurrence in a larger population is warranted.

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Section: Discussionsupporting

confidence: 48%

Usefulness of plasma full‑length glypican‑3 as a predictive marker of hepatocellular carcinoma recurrence after radial surgery

Miura

Fujinami²,

Shimizu³

et al. 2020

Oncol Lett

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“…Regarding the role of PIVKA-II as treatment response marker, a recent meta-analysis showed that increased PIVKA-II levels could predict worsening overall survival and recurrence-free survival in patients with HCC who had curative ablation [48] . More studies are needed to confirm the clinical utility of PIVKA-II for HCC prognosis.…”

Section: Dcpmentioning

confidence: 99%

New and old biomarkers of hepatocellular carcinoma

Zacharakis¹,

AlEid²,

Aldossari³

2018

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Hepatocellular carcinoma (HCC) is a significant cause of mortality in patients with chronic liver disease around the world. Development of biomarkers for early HCC detection is a primary public health goal to decrease mortality. The ideal biomarkers should be highly sensitive and specific for surveillance of high-risk populations and early detection of HCC and also be able to predict therapeutic outcome and provide a prognosis on survival. Currently, the new biomarkers do not perform better than the conventional ones such as alpha-fetoprotein in such a way that they could be widely adopted in clinical practice. Another problem is the low sensitivity of these biomarkers in the detection of HCC. Further work on the development of novel biomarkers and on a combination of them is necessary. Advances in identifying unique molecular signatures including genomic, proteomic, metabolomic, and glycomic profiles have improved our understanding of many biological processes involved in HCC. This review focuses on the role of old and new biomarkers in surveillance, diagnosis, prognosis, and prediction of response to therapeutic targets for HCC and provides up-to-date data to health-care providers which would be applied in clinical practice.

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“…For instance, Kim et al, reported that elevated serum PIVKA-II level was associated with microvascular invasion in small HCC (< 2 cm), and serum PIVKA-II level ≥ 200 mAU/mL was a predisposing factor for tumor recurrence after surgery [22]. Another recent meta-analysis study revealed that higher PIVKA-II could be a predictor of unfavorable overall survival in hepatocellular carcinoma patients receiving curative ablation [23]. Moreover, PIVKA-II has been employed as an important factor in consideration of liver transplantation for HCC patients [24].…”

Section: Discussionmentioning

confidence: 99%

PIVKA-II level is correlated to development of portal vein tumor thrombus in patients with HBV-related hepatocellular carcinoma

Liu

et al. 2019

Infect Agents Cancer

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Aim To evaluate the correlation of serum PIVKA-II levels and development of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) patients. Methods One hundred and twenty-three patients with newly diagnosed HCC were included in this study between March 2016 and October 2018. Thirty-five of these patients were detected with PVTT and all subjects were randomly divided to analysis group ( N = 73) and validation ( N = 50) group. Serum levels of PIVKA-II, laboratory tests including serum aspartate aminotransferase, total bilirubin, platelet count, albumin levels were demonstrated in all the patients. T-test, chi-squared test and logistic regression was used for analyzing data. Diagnostic efficiency and cut-off value of PIVKA-II in PVTT development of HCC patients were calculated using receiver operator curve (ROC) analysis. Results Serum level of PIVKA-II in HCC patients with PVTT was significantly higher than that in HCC patients without PVTT (995.8 mAU/ml vs 94.87 mAU/ml; P = 0.003), as well as D-dimer levels (2.12 mg/L vs 0.56 mg/L P = 0.001). Univariate analysis showed that high serum D-dimer level was an independent risk factor for development of PVTT (OR = 1.22, 95%CI 1.02–1.45). ROC curve showed that among analysis group, the area under ROC curve (AUROC) of PIVKA-II was 0.73 (95%CI 0.59–0.86). For the detection of PVTT in HCC, PIVKA-II had a sensitivity of 83.7% and a specificity of 69.2% at a cutoff of 221.26 mAU/ml, which had a sensitivity of 85.71% and a specificity of 55.56% in validation group, respectively. Conclusion Serum PIVKA-II level is a potential marker for diagnosis of PVTT in HCC patients, which may guide therapeutic strategy and assessment of tumor prognosis of HCC.

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Prognostic value of PIVKA-II in hepatocellular carcinoma patients receiving curative ablation: A systematic review and meta-analysis

Cited by 13 publications

References 37 publications

Usefulness of plasma full‑length glypican‑3 as a predictive marker of hepatocellular carcinoma recurrence after radial surgery

Usefulness of plasma full‑length glypican‑3 as a predictive marker of hepatocellular carcinoma recurrence after radial surgery

New and old biomarkers of hepatocellular carcinoma

PIVKA-II level is correlated to development of portal vein tumor thrombus in patients with HBV-related hepatocellular carcinoma

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