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 Bae,Hyo-Suk Lee,Yoon Jun Kim,Jeong-Hoon Lee,Dae Seog Heo,Jung-Hwan Yoon

doi:10.1186/1471-2407-11-435

Abstract

BackgroundClinicians 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.MethodsPatients 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.ResultsA 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.ConclusionPIVKA-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.

Highlights

Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed
Abbreviation: TACE, transarterial chemoembolization; RFA, radiofrequency ablation; PEI, percutaneous ethanol injection; AFP, alpha-fetoprotein; PIVKA-II, Protein induced by vitamin K absence or antagonist-II; prothombin time (PT), prothrombin time; AST, aspartate aminotransaminase; ALT, alanine aminotransferase. † all were used with continuous variables
Abbreviation: CLD, chronic liver disease; AFP, alpha-fetoprotein; PIVKA-II, Protein induced by vitamin K absence or antagonist-II; PT, prothrombin time; AST, aspartate aminotransaminase; ALT, alanine aminotransferase

Summary

Introduction

Clinicians often experience extrahepatic metastases associated with hepatocellular carcinoma (HCC), even if no evidence of intrahepatic recurrence after treatment is observed. Hepatic resection and liver transplantation are an established curative treatment for early stage HCC patients [1,2,3]. Few good candidates are available for surgical resection and liver transplantation due to surgical risks associated with liver cirrhosis and the limited de novo recurrence or metastases [7,8]. Clinicians experience extrahepatic metastases even if a primary lesion is not found after surgical resection or liver transplantation. If we could determine the patients at increased risk for extrahepatic metastases at an early timepoint with specific predictive factors, we could select good candidates for surgical treatment and prevent unnecessary liver transplantation or surgical resection. The factors that predict metastases, including specific tumor markers, are not yet identified for patients with HCC

Methods

Results

Conclusion