AIM:To evaluate diagnostic value ofα-fetoprotein (AFP)-L3 and prothrombin induced by vitamin K absence-Ⅱ(PIVKA-Ⅱ)in hepatocellular carcinoma(HCC). METHODS:One hundred and sixty-eight patients during routine HCC surveillance were included in this study.Of the 168 patients,90(53.6%)had HCC including newly developed HCC(n=82)or recurrent HCC after treatment(n=8).Sera were obtained during their first evaluation for HCC development and at the time of HCC diagnosis before commencing HCC treatment.HCC was diagnosed by histological examination,appropriate imaging characteristics-computed tomography or magnetic resonance imaging.Control sera were collected from 78 patients with benign liver disease(BLD),which were obtained during routine surveillance with a suspicion of HCC.AFP,AFP-L3 and PIVKA-Ⅱwere measured in the same serum by microchip capillary electrophoresis and liquid-phase binding assay on a micro-total analysis system Wako i30 auto analyzer.The performance characteristics of three tests and combined tests for the diagnosis of HCC were obtained using receiver operating characteristic curves in all populations and subgroups with AFP<20 ng/mL. RESULTS:Of 90 HCC patients,38(42.2%)patients had AFP<20 ng/mL,20(22.2%)patients had AFP 20-200 ng/mL and 32(35.6%)patients had AFP>200 ng/mL.Of the 78 BLD patients,74(94.9%)patients had AFP<20 ng/mL.After adjustment for age and HBV infection status,AFP-L3 levels were higher in HCC than in BLD among patients with low AFP levels(<20 ng/mL)(P<0.001).In a total of 168 patients,areas under the curve(AUC)for HCC were 0.879,0.887,0.801 and 0.939 for AFP,AFP-L3,PIVKA-Ⅱand the combined markers,respectively.The combined AUC for three markers showed higher value than the AUCs of individual marker(P<0.05).AFP-L3 had higher AUC value than PIVKA-Ⅱfor HCC detection in entire patients(P =0.043).With combination of AFP-L3(cut-off>5%) and PIVKA-Ⅱ(cut-off>40 AU/L),the sensitivity were 94.4%and specificity were 75.6%in all patients.In 112 patients with low AFP levels(<20 ng/mL),AUCs of AFP-L3,PIVKA-Ⅱand combine AFP-L3 and PIVKA-Ⅱtests were 0.824,0.774 and 0.939,respectively. AFP-L3 with a cut-off value of 5%showed sensitivity of 71.1%and specificity of 83.8%,and PIVKA-Ⅱwith a cut-off value of 40 AU/L had sensitivity of 57.9%and specificity of 95.9%in patients with low AFP levels. The combination of AFP-L3 and PIVKA-Ⅱincreased the sensitivity and specificity up to 92.1%and 79.7%, respectively,in low AFP group.Combined markers detected 81.8%of early stage HCC(Union for Inter-national Cancer Control stageⅠ),86.7%of small sized tumor(<2 cm)and 91.7%of single tumor of HCC in the low AFP group.In multivariate analysis,AFP-L3 was correlated with AFP and tumor size,and PIVKA-Ⅱwas correlated with laboratory tests including serum aspartate aminotransferase,total bilirubin,platelets and albumin levels.PIVKA-Ⅱhad no correlation with AFP,AFP-L3 or tumor characteristics. CONCLUSION:Combined determination of AFP-L3 and PIVKA-Ⅱcould improve the diagnostic value for HCC detection in patients with or without increased AFP levels. AIM: To evaluate diagnostic value of α-fetoprotein (AFP)-L3 and prothrombin induced by vitamin K-II (PIVKA-II) in hepatocellular carcinoma (HCC). METHODS: One hundred and sixty-eightions during routine HCC surveillance were included In this study.Of the 168 patients,90(53.6%)had HCC that newly developed HCC(n=82)or recurrent HCC after treatment(n=8).Sera were obtained during their first evaluation for HCC development and at the time Of HCC diagnosis before commencing HCC treatment. HCC was diagnosed by histological examination,appropriate imaging characteristics-computed tomography or magnetic resonance imaging.Control sera were collected from 78 patients with benign liver disease(BLD),which is subjected to routine surveillance with a suspicion. Of HCC.AFP,AFP-L3 and PIVKA-IIwere measured in the same serum by microchip capillary electrophoresis and liquid-phase binding assay on a micro-total analysis system Wako i30 auto analyzer.The performance characteristics of th Ree tests and combined tests for the diagnosis of HCC were obtained using receiver operating characteristic curves in all populations and subgroups with AFP<20 ng/mL. RESULTS:Of 90 HCC patients, 38(42.2%)patients had AFP<20 ng/mL , 20(22.2%)patients had AFP 20-200 ng/mL and 32(35.6%)patients had AFP>200 ng/mL.Of the 78 BLD patients, 74(94.9%)patients had AFP<20 ng/mL. After adjustment for age and HBV infection status,AFP-L3 levels were higher in HCC than in BLD among patients with low AFP levels (<20 ng/mL)(P<0.001).In a total of 168 patients,areas under the curve (AUC) for HCC was 0.879,0.887,0.801 and 0.939 for AFP,AFP-L3,PIVKA-II and the combined markers,respectively.The combined AUC for three markers higher value than the AUCs of individual marker (P<0.05). AFP-L3 had higher AUC value than PIVKA-IIfor HCC detection in all patients (P = 0.043). With combination of AFP-L3 (cut-off>5%) and PIVKA-II (cut-off>40 AU/L) ,the sensitivity were 94.4%and specificity were 75.6%in all patients.In 112 patientsWith low AFP levels (<20 ng/mL), AUCs of AFP-L3, PIVKA-II and combine AFP-L3 and PIVKA-IItests were 0.824,0.774 and 0.939,respectively. AFP-L3 with a cut-off value of 5% Showed sensitivity of 71.1% and specificity of 83.8%, and PIVKA-IIwith a cut-off value of 40 AU/L had sensitivity of 57.9% and specificity of 95.9%in patients with low AFP levels. The combination of AFP-L3 and PIVKA. -IIincreased the sensitivity and specificity up to 92.1%and 79.7%, respectively, in AFP group.Combined cookies detected 81.8% of early stage HCC (Union for International Cancer Control stage I), 86.7% of small sized tumor (<2 Cm) and 91.7% of single tumor of HCC in the low AFP group.In multivariate analysis,AFP-L3 was correlated with AFP and tumor size, and PIVKA-IIwas correlated with laboratory tests including serum aspartate aminotransferase, total bilirubin,platelets and albumin levels.PIVKA-IIhad no correlation with AFP,AFP-L3 or tumor characteristics. CONCLUSION:Combined determination of AFP-L3 and PIVKA-IIc Ould improve the diagnostic value for HCC detection in patients with or without increased AFP levels.