Diagnostic Accuracy of PIVKA-II, Alpha-Fetoprotein and a Combination of both in Diagnosis of Hepatocellular Carcinoma in Patients Affected by Chronic HCV Infection

Gentile, Ivan; Buonomo, Antonio Riccardo; Scotto, Riccardo; Zappulo, Emanuela; Carriero, Canio; Piccirillo, Mauro; Izzo, Francesco; Rizzo, Mimma; Cerasuolo, Dionigio; Borgia, Guglielmo; Cavalcanti, Ernesta

doi:10.21873/invivo.11115

Cited by 17 publications

(4 citation statements)

References 18 publications

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“…After studying the association between serum PIVKA-II and AFP levels of the patients included in the study, they did not correlate with each other, in agreement with other studies in which, even dealing with HCC patients, they were not candidates for OLT [36][37][38] . The found results reflect that these two biomarkers are independent of each other, which could be explained by the different synthesis pathways of the two markers in hepatoma cells 39 .…”

Section: Discussionsupporting

confidence: 82%

Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma

Villalba-López

Sáenz-Mateos

Sánchez-Lorencio

et al. 2023

Sci Rep

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The high morbidity and mortality of hepatocellular carcinoma (HCC) has encouraged the search for new biomarkers to be used alongside alpha-foetoprotein (AFP) and imaging tests. The aim of this study was to evaluate the clinical contribution of protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC monitoring after liver transplantation (LT) and compare it with AFP, a routinely used tumour marker. A total of 46 HCC patients (Milan criteria) were enrolled in this study. Serum levels of PIVKA-II and AFP were measured before and after transplantation. Clinical features were determined for all the patients that were included. Significant correlations were found between PIVKA-II expression levels and some clinicopathological features, such as tumour size and number of pre-transplant transarterial chemoembolizations (TACEs). Serum levels of PIVKA-II and AFP decreased significantly after LT and increased in patients with tumour recurrence. Serum PIVKA-II levels may play an important role in predicting disease severity. Furthermore, monitoring PIVKA-II levels in HCC transplant recipients reflects the tumor early recurrence after transplantation and could be used, complementing AFP and imaging tests, as a novel biomarker of this pathology.

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Section: Discussionsupporting

confidence: 82%

Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma

Villalba-López

Sáenz-Mateos

Sánchez-Lorencio

et al. 2023

Sci Rep

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“…Yet, it is likely that using two or three markers in combination will boost the sensitivity of detection. To date, a number of potential biomarkers have been researched in an effort to increase the diagnosis of HCC such as PIVKA-II and AFP [20,22,29].…”

Section: Discussionmentioning

confidence: 99%

Protein Induced by Vitamin K Absence or Antagonist-II Versus Alpha-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis

Kobeissy

Merza

Al-Hillan³

et al. 2023

J Clin Med Res

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Background: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) are promising tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Yet, their diagnostic performance differs throughout HCC investigations. The aim of this meta-analysis was to assess the effectiveness of PIVKA-II and AFP in the diagnosis of HCC.Methods: A systematic literature search was performed to identify relevant studies from eight databases, which were published up to February 2023, in order to compare the diagnostic performance of PIVKA-II and AFP for HCC. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic (SROC) curve was performed to assess the diagnostic accuracy of each biomarker.Results: Fifty-three studies were identified. The pooled sensitivity (95% confidence interval (CI)) of PIVKA-II and AFP was 0.71 (0.70 -0.72) and 0.64 (0.63 -0.65), respectively in diagnosis of HCC, and the corresponding pooled specificity (95% CI) was 0.90 (0.89 -0.90) and 0.87 (0.87 -0.88), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.89 (0.88 -0.90) and 0.78 (0.77 -0.79), respectively. Subgroup analysis demonstrated that PIVKA-II presented higher AUC values compared to AFP in terms of ethnic group (African, European, Asian, and American patients), etiology (mixed-type HCC, hepatitis C virus (HCV)-related, and hepatitis B virus (HBV)-related) and sample size of cases (≤ 100 and > 100). Conclusion:This study reveals that PIVKA-II is a promising biomarker for identifying and tracking HCC, exhibiting greater accuracy than AFP. Our findings indicate that PIVKA-II outperforms AFP in detecting HCC across diverse racial groups and sample sizes, as well as in cases of HBV-related, HCV-related, or mixed-etiology HCC.

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“…Recommended detection methods include US, CT, magnetic resonance imaging and measurement of AFP and PIVKA-II. However, these methods are either cost-intensive, operator-dependent or not suitable for the detection of early HCC[ 6 - 8 , 11 - 13 , 15 ]. Previous publications show that single miRNAs, like miR-21, hsa-miR-26a and hsa-miR-101[ 34 , 35 ], as well as miRNA signatures ( e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Although it has limited sensitivity for early-stage HCC, its addition to US improved sensitivity from 45% to 63% ( P = 0.002)[ 11 , 14 ]. PIVKA-II is more sensitive but less specific than AFP for diagnosis of HCC in patients affected by chronic HCV infection[ 15 ]. Thus, there is a great need for new, non-invasive diagnostic tools to improve the detection of early HCC and eliminate operator-dependent variability.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma

Malik¹,

Klammer²,

Rolny³

et al. 2022

WJG

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BACKGROUND Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein (AFP), protein induced by vitamin K absence/antagonist-II (PIVKA-II) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs (miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including HCC. AIM To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein biomarkers. METHODS Our prospective, multicenter, case-control study recruited 660 participants (354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR ( n = 60) and next-generation sequencing ( n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs (including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-II via real-time quantitative PCR in training ( n = 200) and validation cohorts ( n = 300). RESULTS We identified 26 miRNAs that differentiated chronic liver disease controls from (early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p (miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423 could significantly distinguish ( Q < 0.05) between the HCC and chronic liver disease control groups. In the multivariate setting, miR-21 with PIVKA-II was selected as the best combination, resulting in an area under the curve of 0.87 for diagnosis and area under the curve of 0.74 for early diagnosis of HCC. In the validation cohort, only miR-21 and miR-423 could be confirmed as potential HCC biomarkers. A combination of miRNAs did not perform better than any single miRNA. Improvement of PIVKA-II performance through combination with miRNAs could not be confirmed in the validation panel. Two putative miRs, put-miR-6 and put-miR-99, were tested in the training and validation panels, but their expression could only be detected in very few samples and at a low level (cycle threshold between 31.24 and 34.97). CONCLUSION ...

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Diagnostic Accuracy of PIVKA-II, Alpha-Fetoprotein and a Combination of both in Diagnosis of Hepatocellular Carcinoma in Patients Affected by Chronic HCV Infection

Abstract: Abstract. Background

Cited by 17 publications

References 18 publications

Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma

Usefulness of PIVKA-II for monitoring after liver transplantation in patients with hepatocellular carcinoma

Protein Induced by Vitamin K Absence or Antagonist-II Versus Alpha-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis

Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma

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