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.

1.
Okuda K: Early recognition of hepatocellular carcinoma. Hepatology 1986;6:729–738.
2.
Javadpour N: The role of biologic tumor markers in testicular cancer. Cancer 1980;45(suppl 7):1755–1761.
3.
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.
4.
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.
5.
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.
6.
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.
7.
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.
8.
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.
9.
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.
10.
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.
11.
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.
12.
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.
13.
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.
14.
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.
15.
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.
16.
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.
17.
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.
18.
Llovet JM, Schwartz M, Mazzaferro V: Resection and liver transplantation for hepatocellular carcinoma. Semin Liver Dis 2005;25:181–200.
19.
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.
20.
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.
21.
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.
22.
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.
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