The Impact of PIVKA-II as a Predictor of Hepatocellular Carcinoma Recurrence in Liver Transplant Recipients

PIVKA-II is a highly specific tumor marker for hepatocellular carcinoma (HCC) and is used to detect HCCearly in cirrhosis patients and to assess response to therapy and prognosis in HCC patients. The usefulness ofPIVKA-II in liver transplant recipients with end-stage cirrhosis or with HCC has yet to...

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Published inNippon Shokaki Geka Gakkai zasshi Vol. 40; no. 9; pp. 1549 - 1556
Main Authors Uemoto, Shinji, Ito, Takashi, Takada, Yasutsugu, Fujiki, Masato
Format Journal Article
LanguageJapanese
Published The Japanese Society of Gastroenterological Surgery 2007
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ISSN0386-9768
1348-9372
1348-9372
DOI10.5833/jjgs.40.1549

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Abstract PIVKA-II is a highly specific tumor marker for hepatocellular carcinoma (HCC) and is used to detect HCCearly in cirrhosis patients and to assess response to therapy and prognosis in HCC patients. The usefulness ofPIVKA-II in liver transplant recipients with end-stage cirrhosis or with HCC has yet to be clarified. Materialsand Methods: Subjects were 24 cirrhosis patients without HCC and 123 HCC patients undergoing liver transplantation between 1999 and 2005. Subjects were examined for the PIVKA-II distribution and its correlationwith histopathological findings of HCC and prognosis. Results: We found 58% of cirrhosis patients withoutHCC were positive for PIVKA-II. The mean Child-Pugh and MELD scores in the PIVKA-II positive group (10.8 and 20.9 points) were significantly higher than in the negative group (p<0.05). Of patients with HCC, cumulative recurrence at 5 years was significantly higher in the group with PIVKA-II≤400mAU/ml than inthose with PIVKA-II≤400mAU/ml (60% vs. 13%, p<0.01). Multivariate analysis showed that PIVKA-II exceeding 400mAU/ml was an independent predisposing factor for HCC recurrence (risk ratio, 5.984; p<0.01).Median PIVKA-II in patients with positive microscopic portal venous invasion was significantly higher thanthat in negative patients (p<0.01). Conclusions: High positive ratio of PIVKA-II in patients with cirrhosismay be due to severe liver damage. PIVKA-II is thus a highly useful tumor marker as a predisposing factorfor HCC recurrence of after liver transplantation, which is closely correlated with histopathological features ofHCC.
AbstractList PIVKA-II is a highly specific tumor marker for hepatocellular carcinoma (HCC) and is used to detect HCCearly in cirrhosis patients and to assess response to therapy and prognosis in HCC patients. The usefulness ofPIVKA-II in liver transplant recipients with end-stage cirrhosis or with HCC has yet to be clarified. Materialsand Methods: Subjects were 24 cirrhosis patients without HCC and 123 HCC patients undergoing liver transplantation between 1999 and 2005. Subjects were examined for the PIVKA-II distribution and its correlationwith histopathological findings of HCC and prognosis. Results: We found 58% of cirrhosis patients withoutHCC were positive for PIVKA-II. The mean Child-Pugh and MELD scores in the PIVKA-II positive group (10.8 and 20.9 points) were significantly higher than in the negative group (p<0.05). Of patients with HCC, cumulative recurrence at 5 years was significantly higher in the group with PIVKA-II≤400mAU/ml than inthose with PIVKA-II≤400mAU/ml (60% vs. 13%, p<0.01). Multivariate analysis showed that PIVKA-II exceeding 400mAU/ml was an independent predisposing factor for HCC recurrence (risk ratio, 5.984; p<0.01).Median PIVKA-II in patients with positive microscopic portal venous invasion was significantly higher thanthat in negative patients (p<0.01). Conclusions: High positive ratio of PIVKA-II in patients with cirrhosismay be due to severe liver damage. PIVKA-II is thus a highly useful tumor marker as a predisposing factorfor HCC recurrence of after liver transplantation, which is closely correlated with histopathological features ofHCC.
Author Takada, Yasutsugu
Ito, Takashi
Uemoto, Shinji
Fujiki, Masato
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References 7) Marsh JW, Dvorchik I, Bonham CA et al: Is the pathologic TNM staging system for patients with hepatoma predictive of outcome ? Cancer 88: 538-543, 2000
5) Wiesner R, Edwards E, Freeman R et al: Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 124: 91-96, 2003
9) Kemmer N, Neff G, Kaiser T et al: An analysis of the UNOS liver transplant registry: high serum alpha-fetoprotein does not justify an increase in MELD points for suspected hepatocellular carcinoma. Liver Transpl 12: 1519-1522, 2006
4) 崎園賢治, 老田達雄, 江藤正明ほか: アルコール性肝硬変における血中PIVKA-II上昇の起因の解明. 臨病理50: 289-295, 2002
10) Shimada M, Yonemura Y, Ijichi H et al: Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value. Transplant Proc 37: 1177-1179, 2005
6) Takada Y, Ueda M, Ito T et al: Living donor liver transplantation as a second-line therapeutic strategy for patients with hepatocellular carcinoma. Liver Transpl 12: 912-919, 2006
11) Hamamura K, Shiratori Y, Shiina S et al: Unique clinical characteristics of patients with hepatocellular carcinoma who present with high plasma des-gamma-carboxy prothrombin and low serum alpha-fetoprotein. Cancer 88: 1557-1564, 2000
2) 久保定徳, 松川正明: 肝細胞癌の腫瘍マーカー. 癌と化療31: 2203-2206, 2004
1) Liebman H, Furie BC, Tong MJ et al: Desgamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 310: 1427-1431, 1984
8) Yao FY, Ferrell L, Bass NM et al: Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33: 1394-1403, 2001
3) 松枝由美, 米澤久子: IRMAを用いたPIVKA-II測定キットの基礎的ならびに臨床的検討. 核医技19: 338-345, 2000
12) Koike Y, Shiratori Y, Sato S et al: Des-gammacarboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer 91: 561-569, 2001
References_xml – reference: 4) 崎園賢治, 老田達雄, 江藤正明ほか: アルコール性肝硬変における血中PIVKA-II上昇の起因の解明. 臨病理50: 289-295, 2002
– reference: 12) Koike Y, Shiratori Y, Sato S et al: Des-gammacarboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer 91: 561-569, 2001
– reference: 1) Liebman H, Furie BC, Tong MJ et al: Desgamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N Engl J Med 310: 1427-1431, 1984
– reference: 2) 久保定徳, 松川正明: 肝細胞癌の腫瘍マーカー. 癌と化療31: 2203-2206, 2004
– reference: 6) Takada Y, Ueda M, Ito T et al: Living donor liver transplantation as a second-line therapeutic strategy for patients with hepatocellular carcinoma. Liver Transpl 12: 912-919, 2006
– reference: 3) 松枝由美, 米澤久子: IRMAを用いたPIVKA-II測定キットの基礎的ならびに臨床的検討. 核医技19: 338-345, 2000
– reference: 8) Yao FY, Ferrell L, Bass NM et al: Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33: 1394-1403, 2001
– reference: 10) Shimada M, Yonemura Y, Ijichi H et al: Living donor liver transplantation for hepatocellular carcinoma: a special reference to a preoperative des-gamma-carboxy prothrombin value. Transplant Proc 37: 1177-1179, 2005
– reference: 5) Wiesner R, Edwards E, Freeman R et al: Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 124: 91-96, 2003
– reference: 9) Kemmer N, Neff G, Kaiser T et al: An analysis of the UNOS liver transplant registry: high serum alpha-fetoprotein does not justify an increase in MELD points for suspected hepatocellular carcinoma. Liver Transpl 12: 1519-1522, 2006
– reference: 11) Hamamura K, Shiratori Y, Shiina S et al: Unique clinical characteristics of patients with hepatocellular carcinoma who present with high plasma des-gamma-carboxy prothrombin and low serum alpha-fetoprotein. Cancer 88: 1557-1564, 2000
– reference: 7) Marsh JW, Dvorchik I, Bonham CA et al: Is the pathologic TNM staging system for patients with hepatoma predictive of outcome ? Cancer 88: 538-543, 2000
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SubjectTerms cirrhosis
DCP
hepatocellular carcinoma
liver transplantation
PIVKA-II
Title The Impact of PIVKA-II as a Predictor of Hepatocellular Carcinoma Recurrence in Liver Transplant Recipients
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