英: protein induced by vitamin K absence or antagonist

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/28 17:58:48」(JST)

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Des-gamma carboxyprothrombin (DCP), also known as protein induced by vitamin K absence/antagonist-II (PIVKA-II), is an abnormal form of the coagulation protein, prothrombin. Normally, the prothrombin precursor undergoes post-translational carboxylation (addition of a carboxylic acid group) by gamma-glutamyl carboxylase in the liver prior to secretion into plasma. DCP/PIVKA-II may be detected in people with deficiency of vitamin K (due to poor nutrition or malabsorption) and in those taking warfarin or other medication that inhibits the action of vitamin K.

Diagnostic use [edit]

Hepatocellular carcinoma [edit]

A 1984 study first described the use of DCP as a marker of hepatocellular carcinoma (HCC); it was present in 91% of HCC patients, while not being detectable in other liver diseases. The DCP level did not change with the administration of vitamin K, suggesting a defect in gamma-carboxylation activity rather than vitamin K deficiency.^[1] A number of subsequent studies have since confirmed this phenomenon.^[2]^[3]^[4]

A 2007 comparison of various HCC tumor markers found DCP the least sensitive to risk factors for HCC (such as cirrhosis), and hence the most useful in predicting HCC.^[5] It differentiates HCC from non-malignant liver diseases.^[6]

Despite many years of use in Japan, only did a 2003 American study reevaluate its use in an American patient series. It also identified HCC at an earlier stage.^[4]

Anticoagulant intoxication [edit]

A 1987 report described the use of DCP determination in the detection of intoxication with acenocoumarol, a vitamin K antagonist.^[7]

References [edit]

^ Liebman HA, Furie BC, Tong MJ, et al. (1984). "Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma". N. Engl. J. Med. 310 (22): 1427–31. doi:10.1056/NEJM198405313102204. PMID 6201741.
^ Tsai SL, Huang GT, Yang PM, Sheu JC, Sung JL, Chen DS (1990). "Plasma des-gamma-carboxyprothrombin in the early stage of hepatocellular carcinoma". Hepatology 11 (3): 481–8. doi:10.1002/hep.1840110321. PMID 2155866.
^ Cui R, Wang B, Ding H, Shen H, Li Y, Chen X (2002). "Usefulness of determining a protein induced by vitamin K absence in detection of hepatocellular carcinoma". Chin. Med. J. 115 (1): 42–5. PMID 11930656.
^ ^a ^b Marrero JA, Su GL, Wei W, et al. (2003). "Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients". Hepatology 37 (5): 1114–21. doi:10.1053/jhep.2003.50195. PMID 12717392.
^ Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA (2007). "Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3". Cancer Biomark 3 (2): 79–87. PMID 17522429.
^ Lamerz R, Runge M, Stieber P, Meissner E (1999). "Use of serum PIVKA-II (DCP) determination for differentiation between benign and malignant liver diseases". Anticancer Res. 19 (4A): 2489–93. PMID 10470180.
^ Lefrere JJ, Gozin D (1987). "Use of des-gamma-carboxyprothrombin in retrospective diagnosis of hidden intoxication of anticoagulants". J. Clin. Pathol. 40 (5): 589. doi:10.1136/jcp.40.5.589-b. PMC 1141034. PMID 3584512.

UpToDate Contents

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1. 原発性肝細胞癌の臨床的特徴および診断 clinical features and diagnosis of primary hepatocellular carcinoma
2. 肝臓の合成能の検査（アルブミン、凝固因子、プロトロンビン時間など） tests of the livers biosynthetic capacity eg albumin coagulation factors prothrombin time
3. ビタミンKの概要 overview of vitamin k
4. 慢性肝疾患成人における肝細胞癌の予防およびサーベイランスの推奨 prevention of hepatocellular carcinoma and recommendations for surveillance in adults with chronic liver disease
5. アルコール性脂肪性肝炎およびアルコール性肝硬変の臨床症状および診断 clinical manifestations and diagnosis of alcoholic fatty liver disease and alcoholic cirrhosis

English Journal

Protein Induced by Vitamin K Antagonist-II (PIVKA-II) Is a Reliable Prognostic Factor in Small Hepatocellular Carcinoma.

Kim JM, Hyuck C, Kwon D, Joh JW, Lee JH, Paik SW, Park CK.SourceDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, #50 Ilwon-Dong Gangnam-Gu, Seoul, 135-710, Korea, yjongman21@gmail.com.
World journal of surgery.World J Surg.2013 Jun;37(6):1371-8. doi: 10.1007/s00268-013-1966-0.
BACKGROUND: Hepatocellular carcinoma (HCC) <2 cm in diameter has a favorable prognosis. Therefore surgical resection of small HCC is associated with good outcomes. However, the predisposing factors of prognosis following resection of HCC remain ill-defined. The aims of the present study were to
PMID 23443153

A surgically resected case of AFP and PIVKA-II producing gastric cancer with hepatic metastasis.

Tomono A, Wakahara T, Kanemitsu K, Toyokawa A, Teramura K, Iwasaki T.SourceDivision of Gastrointestinal Surgery, Kobe University Graduate School of Medicine.
Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology.Nihon Shokakibyo Gakkai Zasshi.2013 May;110(5):852-60.
A 78-year-old man was admitted for workup for a liver tumor. Both serum AFP and PIVKA-II levels were high (2260ng/ml and 806mAU/ml, respectively). Contrast-enhanced CT scan and MRI using Gd-EOB-DTPA demonstrated a liver tumor in segment 6 resembling the imaging patterns of hepatocellular carcinoma (
PMID 23648542

Presence of a hypovascular hepatic nodule showing hypointensity on hepatocyte-phase image is a risk factor for hypervascular hepatocellular carcinoma.

Ichikawa S, Ichikawa T, Motosugi U, Sano K, Morisaka H, Enomoto N, Matsuda M, Fujii H, Araki T.SourceDepartment of Radiology, University of Yamanashi, Yamanashi, Japan.
Journal of magnetic resonance imaging : JMRI.J Magn Reson Imaging.2013 Apr 30. doi: 10.1002/jmri.24164. [Epub ahead of print]
PURPOSE: To determine whether the presence of a hypovascular nodule in the liver showing hypointensity on hepatocyte-phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) is a risk factor for hypervascular hepatocellular carcinoma (HCC) in patients with chronic liver disease.MATERIAL
PMID 23633285

Japanese Journal

自然止血していた肝細胞癌破裂に対して腹腔鏡下肝外側区域切除術を施行した1例

河岡徹,深田武久,桑原太一,松隈聰,金子唯,原田俊夫,平木桜夫,福田進太郎
山口医学 62(1), 61-66, 2013-02-01
… 圧痛を伴う上腹部腫瘤.CT, MRI, 超音波検査にてS3に約5cm大,肝表突出型で増大傾向を伴い,早期相で不均一に造影される単発性の肝腫瘍を認めた.肝機能は異常なく,HBs-Ag(－),HCV-Ab(－)であった.術直前のAFPは45071ng/ml, PIVKA-IIは8420mAU/mlと著明高値であった.以上より肝細胞癌を疑い,腹腔鏡下肝外側区域切除術を行うこととした.気腹後,腹腔内を観察したが,少量の血性腹水ならびに小網と膵臓に被覆された肝腫瘍を認め,破裂した肝 …
NAID 120005246299

去勢抵抗性前立腺癌と筋層浸潤性膀胱癌を併発した症例に対しGDC療法が奏効した1例

永田雄大,原貴彦,松山豪泰 [他],松隈聰,金子唯,原田俊夫,平木桜夫,福田進太郎,播磨陽平,浦山直樹,久野興子,松崎祐子,佐貫和俊
西日本泌尿器科 = The Nishinihon journal of urology 75(1), 22-26, 2013-01-00
… 査で腫瘤全体は早期で強く造影され,後期ではwash outされた.MRIではT1強調で低信号,T2強調で一部やや高信号であった.血管造影でも腫瘍は強く濃染された.PET-CTでは腫瘍に^{18}F-FDGの集積を認めなかった.AFPならびにPIVKA-IIは基準値内であった.肝細胞癌など悪性腫瘍の可能性も完全には否定出来ず,増大傾向を認めた為,診断かつ治療目的で,腹腔鏡補助下肝尾状葉突起部部分切除術を施行した.最終診断は肝血管筋脂肪腫(肝AML),筋 …
NAID 120005246292

ソラフェニブ投与により長期PRを得られている慢性腎不全を伴う多発性肝細胞癌患者の1例

石原祐史,杉村直美,堀口徳之,飛鳥井香紀,高口裕規,井上裕介,戸川昭三,長谷川泉,榊原健治,大野智義
肝臓 54(8), 529-534, 2013
… ，MRI検査で多発性肝癌の再発が明らかとなり透析導入は見送られ，血管造影下の治療も施行不可能となった．肝予備能がChild Aであったためソラフェニブを400 mg/日で投与開始した（腫瘍マーカー：AFP 3774 ng/ml，PIVKA-II 14995 mAU/ml）．投与後1週間前後にgrade 3の水様性下痢が出現し，200 mg/日に減量とし症状が安定したので外来フォローとなった．腫瘍マーカーは投与5カ月後には正常化し，MRI検査では多発する腫瘤像は縮小しP …
NAID 130003368703

Related Pictures

Pivka jama kanjon 1 Pivka (river) Železniška postaja Pivka Image illustrative de l'article Pivka Pivka-Žel. postaja Description Pivka station.JPG TURISTIČNO DRUŠTVO PIVKA

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英: protein induced by vitamin K absence or antagonist-II
同: γ-カルボキシル化異常プロトロンビン des-γ-carboxy prothrombin
関: ビタミンK、ワルファリン、肝細胞癌

概念

プロトロンビン(第II因子)のγ-カルボキシル化がビタミンK欠乏などにより障害されて生じる異常プロトロンビン。

ビタミンK依存的にF II, VII, IX, X, Protein C, Protein SのGlu残基がGla(γ-カルボキシグルタミン酸)に変換され、補酵素としてCa2+を利用してリン脂質に結合し、セリンプロテアーゼとしての活性を持つようになる、はずである。ビタミンK非存在下ではこれらの蛋白質はGlu残基のまま、つまり活性を持たないまま末梢血に出現する。これらはそれぞれPIKVA-II,VII,IX,X,PC,PSなどと呼ばれるが、このうちPIVKA-IIがマーカーとして用いられている。

意義

肝細胞癌：直径2cm以下の微小肝細胞癌での陽性率は25-30%

[1] Liebman HA, Furie BC, Tong MJ, et al. (1984). "Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma". N. Engl. J. Med. 310 (22): 1427–31. doi:10.1056/NEJM198405313102204. PMID 6201741.

[2] Tsai SL, Huang GT, Yang PM, Sheu JC, Sung JL, Chen DS (1990). "Plasma des-gamma-carboxyprothrombin in the early stage of hepatocellular carcinoma". Hepatology 11 (3): 481–8. doi:10.1002/hep.1840110321. PMID 2155866.

[3] Cui R, Wang B, Ding H, Shen H, Li Y, Chen X (2002). "Usefulness of determining a protein induced by vitamin K absence in detection of hepatocellular carcinoma". Chin. Med. J. 115 (1): 42–5. PMID 11930656.

[Marreno-4] Marrero JA, Su GL, Wei W, et al. (2003). "Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients". Hepatology 37 (5): 1114–21. doi:10.1053/jhep.2003.50195. PMID 12717392.

[5] Volk ML, Hernandez JC, Su GL, Lok AS, Marrero JA (2007). "Risk factors for hepatocellular carcinoma may impair the performance of biomarkers: a comparison of AFP, DCP, and AFP-L3". Cancer Biomark 3 (2): 79–87. PMID 17522429.

[6] Lamerz R, Runge M, Stieber P, Meissner E (1999). "Use of serum PIVKA-II (DCP) determination for differentiation between benign and malignant liver diseases". Anticancer Res. 19 (4A): 2489–93. PMID 10470180.

[7] Lefrere JJ, Gozin D (1987). "Use of des-gamma-carboxyprothrombin in retrospective diagnosis of hidden intoxication of anticoagulants". J. Clin. Pathol. 40 (5): 589. doi:10.1136/jcp.40.5.589-b. PMC 1141034. PMID 3584512.

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案内

PIVKA