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Open Access Research article

Protein induced by vitamin K absence or antagonist-II production is a strong predictive marker for extrahepatic metastases in early hepatocellular carcinoma: a prospective evaluation

Hyun-Mi Bae12, Jeong-Hoon Lee13, Jung-Hwan Yoon13*, Yoon Jun Kim13, Dae Seog Heo14 and Hyo-Suk Lee13

Author Affiliations

1 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea

2 Division of Oncology, Department of Internal Medicine, Incheon St. Mary's Hospital, Catholic University, Incheon, Korea

3 Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea

4 Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

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BMC Cancer 2011, 11:435  doi:10.1186/1471-2407-11-435

Published: 10 October 2011

Abstract

Background

Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. We investigated the pretreatment predictors of extrahepatic metastases in HCC patients.

Methods

Patients diagnosed with HCC without evidence of extrahepatic metastases were prospectively enrolled. We evaluated the correlation between extrahepatic metastases and pretreatment clinical variables, including serum tumor markers.

Results

A total of 354 patients were included. Seventy-six patients (21%) had extrahepatic metastases during the observation period (median, 25.3 months; range, 0.6-51.3 months). Cox regression multivariate analysis showed that serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) production levels, the intrahepatic tumor stage, platelet count, and portal vein thrombosis were independent risk factors for extrahepatic metastases. Patients with a PIVKA-II production ≥ 300 mAU/mL had a 2.7-fold (95% confidence interval; 1.5-4.8; P < 0.001) and 3.7-fold (95% confidence interval; 2.0-6.6; P < 0.001) increased risk for extrahepatic metastases after adjustment for stage, platelet count, alpha-fetoprotein ≥ 400 ng/mL, and portal vein thrombosis according to the AJCC and BCLC staging systems, respectively.

Conclusion

PIVKA-II production levels might be a good candidate predictive marker for extrahepatic HCC metastases, especially in patients with smaller and/or fewer tumors in the liver with in stages regardless of serum alpha-fetoprotein.

Keywords:
Protein induced by vitamin K absence or antagonist-II; hepatocellular carcinoma; metastases; predictive marker