About 1 in 3 early hepatocellular carcinoma (HCC) patients
are missed with current standard of care 1
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
Ultrasound3
- 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
AFP3-5
- Cirrhosis
- Active hepatitis
- Other types of tumors
- 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
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.
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)
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
Sensitivity
Specificity
AUC
Hear from the regional experts
Hear from clinicians around APAC who have implemented PIVKA-II in their clinical practice, on their experience using PIVKA-II as an aid in the diagnosis of HCC.
Further resources
Want to learn more about HCC and liver disease? Explore the various resources available on Combating Cancer:
References:
- 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. https://doi.org/10.3350/cmh.2019.1001
- 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. https://doi.org/10.1053/j.gastro.2018.01.064
- 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. https://doi.org/10.1111/apt.13841
- 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. https://doi.org/10.3350/cmh.2022.0212
- 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. https://doi.org/10.1007/s00535-015-1129-1
- 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. https://doi.org/10.1056/NEJM198405313102204
- 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. https://doi.org/10.1159/000217667
- 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. https://doi.org/10.18632/oncotarget.20153
- 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. https://doi.org/10.1155/2021/8868370
- 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. https://doi.org/10.1111/j.1572-0241.2006.00443.x
- 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. https://doi.org/10.1371/journal.pone.0153227