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- Highlights and a PDF copy of the latest APAC regional consensus for PIVKA-II and AFP in HCC
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I am Professor Henry Chan, a honorary clinical professor of the Chinese University of Hong Kong and deputy chief hospital manager of Union Hospital Hong Kong.
What is the unmet need in HCC surveillance and diagnosis?
Liver cancer is the 5th commonest cancer and 3rd commonest cancer mortality in Hong Kong. Most patients suffering from liver cancer are having underlying chronic liver disease such as viral hepatitis or fatty liver. As early liver cancer has no symptoms, regular surveillance is required to pick up small cancer, which are potentially curable by liver resection or loco-ablative therapy. On the other hand, systemic therapy for advanced liver cancer is not a very successful option. As patients with chronic liver disease are usually asymptomatic, one challenge on HCC surveillance is adherence of these patients to a regular program. Patient education and convenient testing will be pivotal to the success of HCC surveillance.
What is your current HCC surveillance practice and how is PIVKA-II implemented?
The standard tests for HCC surveillance is ultrasound of the liver and alfa-fetoprotein testing. The recommended interval of surveillance is 6 months to match the tumor doubling time of HCC. As there are limitations for both ultrasound and alfa-fetoprotein, these 2 investigations should be used together. For example, ultrasound may be difficult in patients with liver cirrhosis or obesity. On the other hand, alfa-fetoprotein may have limited sensitivity for small HCC. PIVKA II is a biomarker elevated in HCC with a completely different mechanism as AFP. There are ample data suggesting that testing AFP and PIVKA II together can improve the sensitivity for small HCC.
What clinical situations do you think are the most appropriate to use PIVKA-II for HCC surveillance?
There are data from Japan and China suggesting that AFP is not as sensitive as PIVKA II to detect small HCC in patients with alcohol-related liver disease and non-alcoholic fatty liver disease. Although more studies may be needed to confirm this finding, PIVKA II may be a good biomarker for HCC in patients with liver cirrhosis secondary to these 2 conditions. Another group of patients are those known to have difficult ultrasound, including obese patients and patients with cirrhotic nodules. Adding PIVKA II to the HCC surveillance program may compensate the inadequacy of USG. Ultimately, if cost is not a concern, I think PIVKA II should be used together with AFP in all patients for HCC surveillance.
What are your expectations for digital algorithms that aid in diagnosis of HCC, and how can they add value to overall clinical decisions in addition to biomarkers?
A digital algorithm composed of biomarkers and clinical parameters can generate a single score to inform the probability of HCC. It can facilitate a simple interpretation of the biomarker results in the context of the patients, and will be particularly useful for non-experts to carry out HCC surveillance. One challenge to implement digital algorithms is the education of clinical practitioners to interpret the meaning of the scores.
What advice would you give to your fellow colleagues?
When I was working in the public hospital, I was annoyed by the long waiting time for an ultrasound, which may take up to 2 years. I think PIVKA II is a good alternative for this unmet need. Using PIVKA II together with AFP can improve the sensitivity to pick up early HCC during this window period without ultrasound. This is particularly important for patients with alcohol-related liver disease and non-alcoholic fatty liver when the sensitivity of AFP for early HCC is low.
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- Tokushige, K., et al. (2016),Journal of gastroenterology, 51(6), 586–596
- Guan, M. C., et al. (2022), Hepatobiliary & pancreatic diseases international : HBPD INT, 21(6), 559–568