간세포암종 진단에 유의한 PIVKA-II 값의 제시 - ROC Curve를 이용하여 -
Optimal Cut-off Value of PIVKA-II for Diagnosis of Hepatocellular Carcinoma - Using ROC Curve -
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목적: PIVKA-II (Protein induced by vitamin K absense or antagonist-II)는 간세포암종 진단에 있어서 AFP의 보조 종양표지자로 알려져 있다. 본 연구에서는 간세포암종 및 만성 간질환(만성 간염/간경변) 환자에서 PIVKA-II 값을 측정하여 비교하고, 간세포암종 환자에서 PIVKA-II와 AFP과의 상관관계를 알아보며, 궁극적으로 ROC (receiver operating characteristic) curve 분석을 통해 간세포암종 진단에 유의한 최적의 PIVKA-II 값을 제시하고자 하였다. 대상과 방법: 간세포암종(n=42)과 만성 간질환(n=185)으로 진단받은 227명의 환자를 대상으로 하였다. 간세포암종은 조직검사로 확진하거나 혹은 복부컴퓨터단층촬영, 자기공명영상촬영, 혈관조영술 등에서 2 cm 이상의 고혈관성 종괴가 보이면서 AFP이 400 ng/mL 이상인 경우 임상적으로 진단하였다. PIVKA-II는 electrochemiluminoimmunoassay로 측정하였고, AFP는 immunoradiometric assay로 측정하였으며, 그 기준값은 각각 40 mAU/mL, 20 ng/mL로 하였다. 결과: 간세포암종 환자의 PIVKA-II는 만성 간질환 환자에서 보다 유의하게 높았으며(903.0±1156.7 vs. 111.7±211.0, P<0.01), PIVKA-II와 AFP는 유의한 상관관계를 보였다(P<0.01, r=0.46). PIVKA-II의 간세포암종 진단에 대한 민감도와 특이도는 각각 66.7%, 74.1%였으며, PIVKA-II와 AFP를 동시에 고려한 경우에는 민감도가 85.7%로 증가하였으나 특이도는 64.3%로 감소하였다. PIVKA-II의 ROC curve에서 특이도가 95% 이상이면서 민감도가 급격히 감소하는 지점의 값을 간세포암종 진단의 최적값으로 하였을 때 특이도 95.1%, 민감도 57.1% 지점인 PIVKA-II 값 250 mAU/mL를 간세포암종 진단의 최적값으로 예측하였다. 결론: 본 연구에서 PIVKA-II는 AFP와 같이 만성 간질환으로부터 간세포암종을 구별할 수 있는 종양표지자로서의 역할이 확인되었으며, 250 mAU/mL의 PIVKA-II 값을 간세포암종의 진단에 유의한 최적의 기준값으로 예측하였다.
Abstract
Background/Aims: Protein induced by vitamin K absence or antagonist-II (PIVKA-II), also known as des-carboxyprothrombin (DCP), can be used as an alternative tool to alpha-fetoprotein (AFP) for surveillance of hepatocellular carcinoma (HCC). The aims of the present study were to compare PIVKA- II levels between the patients with HCC and patients with non-HCC chronic liver disease, to evaluate the correlation of PIVKA-II and AFP in HCC patients, and finally to estimate the optimal cut-off value for PIVKA-II for the diagnosis of HCC with using the receiver operating characteristic (ROC) curve. Methods: A total of 227 consecutive patients with HCC (n=42) or chronic liver disease (n=185) were enrolled in this study. HCC was diagnosed histologically or by imaging such as computed tomography, magnetic resonance imaging or angiography. The serum PIVKA-II and AFP levels were measured by electrochemiluminoimmunoassay with using the Haicatch PIVKA-II kit and by immunoradiometric assay, respectively. Results: The PIVKA-II level in the HCC patients was significantly higher than the non-HCC chronic liver disease patients (903.0±1156.7 vs. 111.7±211.0 mAU/ mL, respectively, P<0.01). PIVKA-II and AFP showed a statistical correlation in HCC patients (r=0.46, P<0.01). The sensitivity and specificity of PIVKA-II for the diagnosis of HCC were 66.7% and 74.1%, respectively, and when tasted together with AFP, the sensitivity was increased by 85.7%. For the ROC curve of PIVKA-II in HCC patients, the specificity of a 250 mAU/mL level of PIVKA-II was 95%. Conclusions: PIVKA-II was as useful surveillance tool for differentiating HCC from chronic liver disease, and a PIVKA-II value of 250 mAU/ mL was proposed as a significant cut-off value for diagnosis of hepatocellular carcinoma.
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