Objectives: The aim of this study is to assess the usefulness of prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) in monitoring of recurrent hepatocellular carcinoma (HCC) after curative resection. Methods: From April 2001 to March 2004, a total of 245 patients with histologically proven HCC and 267 non-HCC patients were recruited. Serial follow-up measurements of both alpha-fetoprotein (AFP) and PIVKA-II were performed in 27 patients who had recurrent HCC after resection. Results: In the initial HCC diagnosis, the sensitivity of AFP and PIVKA-II was 48.6% (119/245) and 75.1% (184/245), respectively, at the cutoff of 20 ng/ml for AFP and 40 mAU/ml for PIVKA-II (p < 0.01). The specificity was 81.3% (217/267) and 94.8% (253/267), respectively. When AFP and PIVKA-II were combined, the sensitivity and specificity was 83.3% (204/245) and 77.2% (206/267), respectively. In 27 patients developing recurrent HCC after curative surgical resection, the sensitivity of AFP and PIVKA-II was 40.7% (11/27) and 74.1% (20/27), respectively. Several fluctuating patterns of AFP and PIVKA-II were observed from initial diagnosis to recurrence. Conclusion: Our data suggest that PIVKA-II is a useful tumor marker for HCC, complementary to AFP. Serial measurements of both markers after resection might be helpful for early diagnosis of tumor recurrence.

Okuda K: Early recognition of hepatocellular carcinoma. Hepatology 1986;6:729–738.
Javadpour N: The role of biologic tumor markers in testicular cancer. Cancer 1980;45(suppl 7):1755–1761.
Cui R, He J, Zhang F, Wang B, Ding H, Shen H, Li Y, Chen X: Diagnostic value of protein induced by vitamin K absence (PIVKAII) and hepatoma-specific band of serum gamma-glutamyl transferase (GGTII) as hepatocellular carcinoma markers complementary to α-fetoprotein. Br J Cancer 2003;88:1878–1882.
Liebman HA, Furie BC, Tong MJ, Blanchard RA, Lo KJ, Lee SD, Coleman MS, Furie B: Des-γ-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 1984;310:1427–1431.
Fujiyama S, Izuno K, Gohshi K, Shibata J, Sato T: Clinical usefulness of des-gamma-carboxy prothrombin assay in early diagnosis of hepatocellular carcinoma. Dig Dis Sci 1991;36:1787–1792.
Aoyagi Y, Oguro M, Yanagi M, Mita Y, Suda T, Suzuki Y, Hata K, Ichii K, Asakura H: Clinical significance of simultaneous determinations of alpha-fetoprotein and des-gamma-carboxy prothrombin in monitoring recurrence in patients with hepatocellular carcinoma. Cancer 1996;77:1781–1786.
Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA: Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: A comparison of AFP, DCP, and AFP-L3. Cancer Biomarkers 2007:79–87.
Kasahara A, Hayashi N, Fusamoto H, Kawada Y, Imai Y, Yamamoto H, Hayashi E, Ogihara T, Kamada T: Clinical evaluation of plasma des-γ-carboxy prothrombin as a marker protein of hepatocellular carcinoma in patients with tumors of various sizes. Dig Dis Sci 1993;38:2170–2176.
Suehiro T, Matsumura T, Itasaka H, Taketomi A, Yamamoto K, Sugimachi K: Des-gamma-carboxy prothrombin and proliferative activity of hepatocellular carcinoma. Surgery 1995;117:682–691.
Fujiyama S, Morishita T, Sagara K, Motohara K, Matsuda I: Clinical evaluation of plasma abnormal prothrombin (PIVKA-II) in patients with hepatocellular carcinoma. Hepatogastroenterology 1986;33:201–205.
Fujiyama S, Morishita T, Hashiguchi O, Sato T: Plasma abnormal prothrombin (des-gamma-carboxy prothrombin) as a marker of hepatocellular carcinoma. Cancer 1988;61:1621–1628.
Kim JK, Han KH, Lee JT, Paik YH, Ahn SH, Lee JD, Lee KS, Chon CY, Moon YM: Longterm clinical outcome of phase IIb clinical trial of percutaneous injection with holmium-166/chitosan complex (Milican) for the treatment of small hepatocellular carcinoma. Clin Cancer Res 2006;12:543–548.
Tsai SL, Huang GT, Yang PM, Sheu JC, Sung JL, Chen DS: Plasma des-gamma-carboxyprothrombin in the early stage of hepatocellular carcinoma. Hepatology 1990;11:481–488.
Grazi GL, Mazziotti A, Legnani C, Jovine E, Miniero R, Gallucci A, Palareti G, Gozzetti G: The role of tumor markers in the diagnosis of hepatocellular carcinoma, with special reference to the des-gamma-carboxy prothrombin. Liver Transplant Surg 1995;1:249–255.
Ishii M, Gama H, Chida N, Ueno Y, Shinzawa H, Takagi T, Toyota T, Takahashi T, Kasukawa R: Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence or for detecting hepatocellular carcinoma. South Tohoku District Study Group. Am J Gastroenterol 2000;95:1036–1040.
Nakamura S, Nouso K, Sakaguchi K, Ito YM, Ohashi Y, Kobayashi Y, Toshikuni N, Tanaka H, Miyake Y, Matsumoto E: Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol 2006;101:2038–2043.
Marrero JA, Su GL, Wei W, Emick D, Conjeevaram HS, Fontana RJ, Lok AS: Des-gamma-carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in American patients. Hepatology 2003;37:1114–1121.
Llovet JM, Schwartz M, Mazzaferro V: Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 2005;25:181–200.
Cha C, Fong Y, Jarnagin WR, Blumgart LH, DeMatteo RP: Predictors and patterns of recurrence after resection of hepatocellular carcinoma. J Am Coll Surg 2003;197:753–758.
Pawlik TM, Poon RT, Abdalla EK, Zorzi D, Ikai I, Curley SA, Nagomey DM, Belghiti J, Ng IO, Yamaoka Y, Lauwers GY, Vauthey JN: International Cooperative Study Group on Hepatocellular Carcinoma. Critical appraisal of the clinical and pathologic predictors of survival after resection of large hepatocellular carcinoma. Arch Surg 2005;140:450–457.
Shah SA, Cleary SP, Wei AC, Yang I, Taylor BR, Hemming AW, Langer B, Grant DR, Greig PD, Gallinger S: Recurrence after liver resection for hepatocellular carcinoma: risk factors, treatment, and outcomes. Surgery 2007;141:330–339.
Tateishi R, Shiina S, Yoshida H, Teratani T, Obi S, Yamashiki N, Yoshida H, Akamatsu M, Kawabe T, Omata M: Prediction of recurrence of hepatocellular carcinoma after curative ablation using three tumor markers. Hepatology 2006;44:1518–1527.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.