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

Do Young Kim, Bao Nguyen Toan, Chee Kiat Tan, Irsan Hasan, Lyana Setiawan, Ming Lung Yu, Namiki Izumi, Nguyen Nguyen Huyen, Pierce Kah Hoe Chow, Rosmawati Mohamed, Stephen Lam Chan, Tawesak Tanwandee, Teng Yu Lee, Thi Thanh Nguyen Hai, Tian Yang, Woo Chang Lee, Henry Lik Yuen Chan

Research output: Contribution to journalReview articlepeer-review

17 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)277-292
Number of pages16
JournalClinical and molecular hepatology
Issue number2
Publication statusPublished - 1 Apr 2023


  • Alpha-fetoprotein
  • Biomarkers
  • Carcinoma, hepatocellular
  • Consensus


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