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Review
. 2023 Apr;29(2):277-292.
doi: 10.3350/cmh.2022.0212. Epub 2023 Jan 30.

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region

Do Young Kim  1 , Bao Nguyen Toan  2 , Chee-Kiat Tan  3 , Irsan Hasan  4 , Lyana Setiawan  5 , Ming-Lung Yu  6   7 , Namiki Izumi  8 , Nguyen Nguyen Huyen  9 , Pierce Kah-Hoe Chow  10   11 , Rosmawati Mohamed  12 , Stephen Lam Chan  13 , Tawesak Tanwandee  14 , Teng-Yu Lee  15   16 , Thi Thanh Nguyen Hai  9   17 , Tian Yang  18 , Woo-Chang Lee  19 , Henry Lik Yuen Chan  20
Affiliations
Review

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region

Do Young Kim et al. Clin Mol Hepatol. 2023 Apr.

Abstract

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Keywords: Alpha-fetoprotein; Biomarkers; Carcinoma, hepatocellular; Consensus; PIVKA-II.

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Conflict of interest statement

Conflicts of Interest

This study did not include the use of human or animal subjects.

Below is the list of conflict-of-interest statements: Kim DoYoung, Toan Bao Nguyen, Setiawan Lyana, Huyen Nguyen Nguyen, Mohamed Rosmawati, Hai Thi Thanh Nguyen and Lee Woo-Chang declare that they have no conflict of interest.

Tan Chee-Kiat has received honoraria made to his institution for lectures, presentations, speakers bureaus, manuscript writing and education events from Abbott Laboratories, Astellas and Gilead Sciences. He has also received payment made to his institution for participation on a Data Safety Monitoring Board and Advisory Board for Abbott Laboratories, Bayer, Eissai, Gilead Sciences and Roche Diagnostics.

Hasan Irsan has received honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and education events from Eisai and Roche.

Yu Ming-Lung has received grants from Abbott, BMS, Gilead and Merck. He has also received consulting fees and honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and education events from Abbott, Abbvie, BMS, Gilead, IPSEN, Merck, Roche and Roche Diagnostics.

Namiki Izumi has received honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and education events from Chugai, Eisai and Takeda.

Chow Pierce Kah-Hoe has received grants from AMiLi, MiRXES, Perspectum and Roche. He has received consulting fees for Beigene, Omega Therapeutics and Worrell (LLC), and honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and education events from Abbott, AstraZeneca, Eisai, Roche and Sirtex Medical. He has a patent submitted for “A system and method for classify cancer patients into appropriate cancer treatment groups and compounds for treating the patients. Pub. No.: WO/2019/108135 A1 International; Application No.: PCT/SG2018/050585. He has received payment for participating on Data Safety monitoring Boards and Advisory Boards from AstraZeneca, AUMBioscience, Genentech, Roche, Singapore-Samsung Medical Centre (SG-SMC) Joint Lab and Sirtex Medical. In addition, he declares having stock or stock options in AVATAMED Pte. Ltd.

Chan Stephen Lam has received consulting fees and honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and education events from AstraZeneca, Eisai and MSD. He has participated on a Data Safety Monitoring Board and Advisory Board for AstraZeneca.

Tanwandee Tawesak has received grants from Gilead, Janssen, MSD, Roche and Vir Biotech.

Lee Teng-Yu has received grants from Gilead, MSD and Roche. He has received consulting fees and honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and education events from AbbVie, BMS, Eisai, Gilead and Roche. He has participated on Advisory Boards for BMS, Eisai, Gilead and Roche.

Yang Tian has received honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and education events from Abbott and Roche.

Chan Henry Lik Yuen has received consulting fees from AbbVie, Aligos, Arbutus, Hepion, Gilead, GSK, Janssen, Roche, Vaccitech, Vir Biotechnology and Virion Therapeutics.

He has received honoraria for lectures, presentations, speakers’ bureaus, manuscript writing and education events from Gilead, Roche and Viatris, and received support for attending an overseas conference from Gilead. He has participated on Data Safety Monitoring Boards for Aligos, Roche and Vaccitech.

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