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Get the latest updates in the liver space with our HCC detection (HD) expert pack

Get the latest updates in the liver space with our HCC detection (HD) expert pack


  • Highlights and a PDF copy of the latest APAC regional consensus for PIVKA-II and AFP in HCC
  • APASL 2023 Congress Report
  • Updates on future studies and patient cases
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About 1 in 3 early hepatocellular carcinoma (HCC) patients
are missed with current standard of care 1

patients image

Ultrasound + AFP has only 63% sensitivity in detecting early stage HCC2

37% are missed

This means that 37% patients are missing out on potentially curative HCC treatment.

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The gaps in current standard of care

HCC detection US icon


  • Operator variability
  • Poor performance in patients with fibrotic changes and fatty infiltration of the liver
  • Difficult to perform on obese patients 
  • Difficult to detect small tumors (< 2cm)
  • Limited capacity in public hospitals and rural settings
HCC detection AFP icon


Sensitivity and specificity depends on cut-off values used AFP can be elevated (false positive) in:
  • Cirrhosis
  • Active hepatitis
  • Other types of tumors
AFP can be normal (false negative) in:
  • Certain HCC patients have normal AFP throughout the entire disease course. This can be dependent on the etiology of the disease (e.g. high prevalence of AFP-negative in patients with fatty liver disease  induced HCC)
  • Small HCC tumors (<2cm)

PIVKA-II + AFP improves detection of early HCC with increased sensitivity compared to AFP alone

PIVKA-II is a protein that is elevated in the liver under certain circumstances, such as HCC and Vitamin K deficiency6,7.

HCC Dection cc PIVKA II graphic

In the recent 2022 'Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region', experts agree that PIVKA-II, when combined with AFP, improves the detection of HCC, compared to either biomarker alone4.

HCC detection all stage
HCC detection early stage

Experts also agree that PIVKA-II is valuable in the detection of HCC in AFP-negative HCC patients4.

Many patients with HCC are AFP-negative (defined as AFP ≤20 ng/ml)

HCC Dection cc Pie chart
HCC AFP mobile

Almost Half (46%) of 1,158 patients with HCC were AFP-negative10

PIVKA-II can detect up to 76% of patients with AFP-negative HCC11


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  1. Hanouneh, I. A., Alkhouri, N., & Singal, A. G. (2019). Hepatocellular carcinoma surveillance in the 21st century: Saving lives or causing harm?. Clinical and molecular hepatology, 25(3), 264–269.
  2. Tzartzeva, K., Obi, J., Rich, N. E., Parikh, N. D., Marrero, J. A., Yopp, A., Waljee, A. K., & Singal, A. G. (2018). Surveillance Imaging and Alpha Fetoprotein for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis: A Meta-analysis. Gastroenterology, 154(6), 1706–1718.e1.
  3. Simmons, O., Fetzer, D. T., Yokoo, T., Marrero, J. A., Yopp, A., Kono, Y., Parikh, N. D., Browning, T., & Singal, A. G. (2017). Predictors of adequate ultrasound quality for hepatocellular carcinoma surveillance in patients with cirrhosis. Alimentary pharmacology & therapeutics, 45(1), 169–177.
  4. Kim, D. Y., Toan, B. N., Tan, C. K., Hasan, I., Setiawan, L., Yu, M. L., Izumi, N., Huyen, N. N., Chow, P. K., Mohamed, R., Chan, S. L., Tanwandee, T., Lee, T. Y., Hai, T. T. N., Yang, T., Lee, W. C., & Chan, H. L. Y. (2023). Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region. Clinical and molecular hepatology, 29(2), 277–292.
  5. Tokushige, K., Hyogo, H., Nakajima, T., Ono, M., Kawaguchi, T., Honda, K., Eguchi, Y., Nozaki, Y., Kawanaka, M., Tanaka, S., Imajo, K., Sumida, Y., Kamada, Y., Fujii, H., Suzuki, Y., Kogiso, T., Karino, Y., Munekage, K., Kuromatsu, R., Oeda, S., … Hashimoto, E. (2016). Hepatocellular carcinoma in Japanese patients with nonalcoholic fatty liver disease and alcoholic liver disease: multicenter survey. Journal of gastroenterology, 51(6), 586–596.
  6. Liebman, H. A., Furie, B. C., Tong, M. J., Blanchard, R. A., Lo, K. J., Lee, S. D., Coleman, M. S., & Furie, B. (1984). Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. The New England journal of medicine, 310(22), 1427–1431.
  7. Ono, M., Ohta, H., Ohhira, M., Sekiya, C., & Namiki, M. (1990). Measurement of immunoreactive prothrombin precursor and vitamin-K-dependent gamma-carboxylation in human hepatocellular carcinoma tissues: decreased carboxylation of prothrombin precursor as a cause of des-gamma-carboxyprothrombin synthesis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 11(6), 319–326. 
  8. Chen, H., Chen, S., Li, S., Chen, Z., Zhu, X., Dai, M., Kong, L., Lv, X., Huang, Z., & Qin, X. (2017). Combining des-gamma-carboxyprothrombin and alpha-fetoprotein for hepatocellular carcinoma diagnosing: an update meta-analysis and validation study. Oncotarget, 8(52), 90390–90401. 
  9. Xu, F., Zhang, L., He, W., Song, D., Ji, X., & Shao, J. (2021). The Diagnostic Value of Serum PIVKA-II Alone or in Combination with AFP in Chinese Hepatocellular Carcinoma Patients. Disease markers, 2021, 8868370.
  10. Farinati, F., Marino, D., De Giorgio, M., Baldan, A., Cantarini, M., Cursaro, C., Rapaccini, G., Del Poggio, P., Di Nolfo, M. A., Benvegnù, L., Zoli, M., Borzio, F., Bernardi, M., & Trevisani, F. (2006). Diagnostic and prognostic role of alpha-fetoprotein in hepatocellular carcinoma: both or neither?. The American journal of gastroenterology, 101(3), 524–532.
  11. Ji, J., Wang, H., Li, Y., Zheng, L., Yin, Y., Zou, Z., Zhou, F., Zhou, W., Shen, F., & Gao, C. (2016). Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale, Multicentre Study. PloS one, 11(4), e0153227.

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