Lead Liver LP
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Speaker

Prof. Henry CHAN

Hepatologist
Deputy Chief Hospital Manager,
Union Hospital Hong Kong Honorary Clinical Professor,
Faculty of Medicine, The Chinese University of Hong

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Moderator & Speaker

Assoc. Prof. Teerha Piratvisuth

NKC Institute of Gastroenterology and Hepatology
Prince of Songkla University, Thailand

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Live Q&A

Prof.Henry CHAN

Assoc. Prof. Teerha Piratvisuth

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Moderator

Prof. Chiun HSU

Medical oncologist
Professor, National Taiwan University
Director, National Taiwan University Cancer Center
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Speaker

Prof. Henry CHAN

Hepatologist
Deputy Chief Hospital Manager,
Union Hospital Hong Kong Honorary Clinical Professor,
Faculty of Medicine, The Chinese University of Hong
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Speaker

Prof. Hui Chuan SUN

Surgeon
Deputy Head, Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital,
Fudan University, Shanghai, China
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Key Highlights

PIVKA-II and GAAD score are the promising tools for HCC surveillance

  • The levels of PIVKA-II correlate with HCC staging and aggressiveness.
  • PIVKA-II increases the sensitivity of HCC detection as compared to AFP.
  • The Elecsys GAAD algorithm, combining PIVKA-II and AFP, plus age and gender, demonstrated good clinical performance in differentiating HCC and benign chronic liver disease, across all disease stages and etiologies
  • For the detection of both early- and all-stage HCC, the Elecsys GAAD score performed better than Elecsys AFP alone

Values of biomarkers AFP & PIVKA-II in HCC treatment monitoring

  • AFP responses correlate with the effectiveness of HCC resection
  • Decrease in AFP levels are associated with objective response and longer OS & PFS after atezolizumab + Bevacizumab treatment in unresectable HCC
  • Patients with a decrease in AFP or PIVKA-II had a higher radiological response rate after HCC immunotherapy

Questions & Answers

The use of biomarkers in patients with different etiology: Use of PIVKA-II might not be limited to HCC etiology whereas AFP may be more useful in HBV-HCC. Could you elaborate more on the potential difference in the biology between AFP and PIVKA-II as to why PIVKA-II is unaffected by the underlying etiology?

Prof Chan: The problem with AFP is that in some kinds of HCC, AFP level may not be elevated in those patients. PIVKA-II, on the other hand, its biochemistry is due to problems in the carboxylation process and this is pre-cancer specific. No matter the etiology, HCC will affect the carboxylation process of the prothrombin precursor PIVKA-II. As such, PIVKA-II levels will be elevated, so it gives an independent pathway to select another biomarker that is better than AFP and can work with AFP to improve the entire algorithm of HCC surveillance.

Elevation of PIVKA-II correlates well with HCC stage in terms of BCLC system. Do you consider PIVKA-II level to be potential prognosis factor for HCC?

Prof Chan: We will need to work with our surgery and oncology colleagues to further studies on this. Prognosis is primarily dependent on the size of HCC and the efficacy of treatment. By monitoring the level of tumor biomarkers, we hope to know whether the tumor is cleared or has recurred. The study will need to be an entire package and not just about a single biomarker level change or its role in screening.

Prof Sun: It is mainly useful for prognosis for newly diagnosed HCC, treated by either surgery or systemic therapies. According to our own experience, we compared performance of prediction by AFP and PIVKA- II, we believe PIVKA-II may have more heterogeneous origin of cells because after resection of early HCC

we found 20% of patients may have increased PVIKA-II levels compared with pre-operative PIVKA-II levels. I do not know the reason but PIVKA-II may be produced by other cells during surgery. We also noticed around 10% of patients have increased PIVKA-II after receiving systemic therapies even if the tumor size has been shrunk. So the discrepancy of PIVKA-II and tumor size might suggest there are other cells producing PIVKA-II. More investigations is required. Another point is Roche may have better test kits so I believe we should unify the testing kit so we may have better comparison between studies.

Prof Chan: We found that PIVKA-II level is also associated with micro-vascularization on top of BCLC staging.

Prof Hsu: PIVKA-II elevation after surgery might be due to liver regeneration, as we know that after resection, during the regeneration process there are also some increase in cytokines as reported in some studies.

Regarding the use of PIVKA-II in monitoring treatment response for patients who receive immune checkpoint inhibitor based therapy – there is an early decrease of tumor biomarkers. Could you elaborate more on what is the best schedule for monitoring of PIVKA-II and AFP?

Prof Sun: We have observed around 100 patients who received systemic therapies. In our practice, we test PVIKA-II and AFP every 3 weeks when patients receive PD-1 antibodies to observe the dynamic change of the biomarkers. Our hypothesis is to observe early decrease of AFP and/or PIVKA-II, which is associated with tumor response. This will allow us to shift patients to different systemic therapies if tumor response is not as good.

Do you consider any specific patient population that PIVKA-II should be added in the diagnosis and monitoring?

Prof Chan: As a whole, putting 2 biomarkers together can really increase the sensitivity of picking up early stage HCC – using both is better than one. Prof Sun: I agree – in our hospital, we use AFP, PIVKA-II and AFP-L3 test in every HCC patient, our experience is that the performance is better with more biomarkers to evaluate response or for early diagnosis. However, we do not yet have detailed data to support this so we expect to use GAAD or GALAD for early diagnosis and response evaluation.

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