PIVKA-II Levels Research Articles

Immunohistochemical studies of PIVKA-II in hepatocellular carcinoma by indirect immunofluorescence.

Tissue PIVKA-II was examined in 32 hepatocellular carcinomas and 2 metastatic liver tumors using indirect immunofluorescence, and the results were compared with the size, histological grading and serum PIVKA-II level. The specificity of this method was confirmed by the disappearance of reactivity in PLC/PRF/5 cells after the addition of vitamin K to the culture medium. Positive PIVKA-II staining was observed as a clustered or a single cell pattern only in the HCC nodules, but not in the surrounding cirrhotic tissue. PIVKA-II staining was observed in all HCC groups regardless of histological grade. There was no relationship between PIVKA-II staining and the size of HCC. PIVKA-II was detected immunohistochemically even in small HCC of patients whose plasma PIVKA-II levels were below the detection limit. These results suggest that PIVKA-II production is a specific phenotype of HCC regardless of its histological grading and demonstrate that this immunofluorescent PIVKA-II staining is more sensitive and useful than plasma PIVKA-II assay for the diagnosis of HCC.

Usefulness of the high sensitivity PIVKA-II measurement method in diagnosis of hepatocellular carcinoma: A comparison with the conventional method

We investigated a new PIVKA-II assay kit (Eizai, ED-008) that incorporates the use of an improved secondary antibody compared with the conventional EIA method, and is highly sensitive to PIVKA-II (sensitivity: 0,0125 AU/ml). Using this new kit, we measured plasma PIVKA-II levels in 76 subjects in whom the conventional PIVKA-II assay was negative (≤ 0.0625 AU/ml). There were 30 patients with HCC, 14 patients with liver cirrhosis (six with α-fetoprotein ≥ 50 ng/ml), 11 patients with chronic active hepatitis C, 11 patients with chronic inactive hepatitis C, and ten healthy volunteers. The new assay kit detected PIVKA-II (≥ 0.0125 AU/ml) in 11 patients with HCC (36.7%), and one patient with liver cirrhosis (7.1%), but was negative in the patients with chronic active or inactive hepatitis C and the controls. Among the 11 HCC patients positive for PIVKA-II, the plasma α-fetoprotein level was greater than 100 ng/ml in two patients (18.2%), while it was above this level in three of the 19 patients negative for PIVKA-II. The mean size of the main tumor in the patients positive and negative for PIVKA-II was 2.16 + 0.87 cm and 2.62 + 1.50 cm, respectively, with no significant difference between the groups (P = 0.47). However, in seven patients positive for PIVKA-II, the tumor size was less than 2 cm. This assay also showed a high specificity for HCC (0.98). We concluded that this assay may allow PIVKA-II to be used as a more effective indicator of HCC.

肝癌の肝動脈塞栓術後のＰＩＶＫＡ‐ＩＩとＡＦＰの推移 腫よう壊死効果との相関の比較および実測半減期の比較

血漿PIVKA-IIと血清AFPの両方が陽性であった未治療の切除不能肝癌患者26名でTAEの術前から術後の各週のPIVKA-IIとAFPの推移,および1週めのX線CT像の腫瘍壊死率の関係を検討した.TAE後1週めでは腫瘍壊死率にPIVKA-IIの推移が有意に相関(γ=0.7)したが同じ時期のAFPの推移は腫瘍壊死率に相関(γ=0.2)しなかった.TAE後2, 3週めはPIVKA-II, AFPとも有意に相関した.TAE後腫瘍壊死率90%以上の16例におけるPIVKA-IIの実測半減期(AHL)は44時間が最短で,すべてのAHLのうちの75%はTAE後2日めから4日めの間に集中し平均のAHLは3.2日であった.一方AFPのAHLは2.98日が最短でまばらに分布し平均は6日であった.またこれらの肝癌TAE後のPIVKA-IIとAFPの推移の特徴の違いからTAE後1週めの効果判定にはPIVKA-IIがAFPより有用であることが示唆された.またこれらの結果は肝癌TAE後の効果判定におけるPIVKA-IIとAFPの有用性を支持すると考えられた.

Changes in the plasma abnormal prothrombin level following treatment of hepatocellular carcinoma

The Hokkaido Liver Cancer Study Group focused on the changes in PIVKA-II levels observed in 61 HCC patients after several regimens of treatment in comparison with the AFP levels and the pathophysiological characteristics of HCC. The overall positivity rate for PIVKA-II was 47%, and there was no correlation between the PIVKA-II values and the AFP levels. Accordingly, the HCC detection rate was increased by about 20% by the measurement of both markers. In all, 13 patients underwent hepatic resection, and nonsurgical therapy was carried out in the other 48 subjects. Of the 6 surgically treated patients, 5 (83%) showed a fall in PIVKA-II levels to the normal range immediately after surgery, whereas 14/29 (48%) subjects receiving nonsurgical treatment showed a decrease in PIVKA-II values. Although inconsistency between these tumor markers was detected in four treated cases, we concluded that assay for both of these two parameters may expand their clinical utility for the diagnosis of HCC and monitoring of patients after treatment.

Evaluation of des-γ-carboxy prothrombin as a marker protein of hepatocellular carcinoma

We measured des-gamma-carboxyglutamic acid prothrombin (protein induced by vitamin K absence or antagonist-Factor II: [PIVKA-II]) in plasmas of normal subjects, patients with thrombotic disease, those with hepatic disease including hepatocellular carcinoma, and those with carcinoma of other tissues, and compared the results with results of blood coagulation tests used for the examination of hepatic function. In addition, in the patients with hepatic disease, PIVKA-II and alpha-fetoprotein (AFP) levels were compared. The PIVKA-II level was frequently high in patients with thrombotic disease given warfarin therapy and those with hepatocellular carcinoma. However, in patients with thrombotic disease who were not given warfarin therapy, no significant correlation was seen between the PIVKA-II value and the results of the thrombotest or hepaplastin test, suggesting no association between the PIVKA-II level and the degree of impairment of hepatic function. In 70 patients with hepatocellular carcinoma, the percentage of patients positive for PIVKA-II (greater than or equal to 0.1 micrograms/ml) and those positive for AFP (greater than or equal to 20 ng/ml) were similar (77% and 74%, respectively). Pearson's correlation of coefficient between the PIVKA-II value and the AFP value in the 70 patients was 0.463. However, false-positive rates in patients with hepatic disease other than hepatocellular carcinoma were lower for PIVKA-II. Combined assessment of PIVKA-II and AFP increased positive rates and allowed exclusion of false-positive patients. The plasma PIVKA-II level is suggested to be useful as an indicator of warfarin control in patients with thrombotic disease, as a marker of hepatocellular carcinoma, and is particularly of value when assessed in combination with AFP.

THE CLINICAL SIGNIFICANCE OF PIVKA-II MEASUREMENT IN PATIENTS WITH PRIMARY HEPATIC TUMOR

The clinical significance of PIVKA-II measurement in primary liver cancer was studied. The level of PIVKA-II was normal in all 78 healthy volunteers but it was elevated in 54.7% (35/64 cases) of patients with hepatocellular carcinoma (HCC) and 62.5% (5/8 cases) of patients with cholangiocellular carcinoma (CCC). PIVKA-II was positive in 43.8% (7/16 cases) of α-fetoprotein negative patients with HCC. Combined measurement of PIVKA-II with α-fetoprotein revealed that the positive rate of tumor marker in HCC was increased by about 10% when compared to the sole determination of α-fetoprotein (75.1%). The values from hepaplastin test and thrombotest, and vitamin K dependent factors were not correlated to the plasma levels of PIVKA-II in patients with HCC. These values were increased in PIVKA-II positive patients with HCC when compared to PIVKA-II negative patients. No significant difference in II/V ratio was noted between PIVKA-II positive and negative groups. The levels of vitamin K dependent factors were also relatively high in patients with CCC. Thus, it is suggested that PIVKA-II positive patients whose vitamin K dependent factors and II/V ratio are within normal limit may suffer from the primary hepatic tumor and thereby should be chekced by the radiological examinaitons to demonstrate a possible involvement of hepatic malignancy.

肝・胆道・すい疾患におけるＰＩＶＫＡ‐ＩＩ測定の意義

肝・胆道・すい疾患におけるＰＩＶＫＡ‐ＩＩ測定の意義

高地住民妊婦の凝固線溶動態と胎盤内凝固との関連性

The serial pathologic studies of placenta examined in Nepal of high mountain country since 1977 were compared with those of Japanese placentas. As the most characteristic findings of Nepalese placentas, massive subchorionic fibrin deposits were observed. In this paper, in order to find a cause of such a high incidence of intraplacental coagulation, coagulation and fibrinolytic states of 160 Nepalese pregnant women from 20 to 40 weeks of gestation were investigated and compared with those of Japanese pregnant women.Results: 1) Levels of fibrinolytic inhibitors of α1-AT, α2-MG, α2-PI and C1-INA in Nepalese group were higher than those of Japanese group, while AT-III levels were lower than those of Japanese women group. 2) No significant differences of PTT as well as concentrations of fibrinogen, plasminogen and FDP were found in both groups, but FVIII value showed significantly high in Nepalese group. 3) Prekallikrein and kallikrein levels in Nepalese group were much higher than those of Japanese group. 4) Protein C levels in Nepalese pregnant women were less than those of Japanese group, while levels of PIVKA-II over 1μg/ml in Nepalese group amounted to 45%.In conclusion, in general, Nepalese pregnant women at high land have a tendency of hypercoagulable state which might lead to intraplacental hypercoagulation.