Alpha-fetoprotein,protein induced by vitamin K absence or antagonist-Ⅱ,lens culinaris agglutinin-reactive fraction of alpha-fetoprotein alone and in combination for early detection of hepatocellular carcinoma from nonalcoholic fatty liver disease:A multicenter analysis

Background:Current surveillance strategies for hepatocellular carcinoma(HCC)among patients with non-alcoholic fatty liver disease(NAFLD)are insufficient.This study aimed to investigate the diagnostic perfor-mance of alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ),lens culinaris agglutinin-reactive fraction of AFP(AFP-L3),and their combinations in HCC underlying NAFLD patients.Methods:Serologic AFP,AFP-L3,and PIVKA-Ⅱ levels in NAFLD patients with and without HCC were mea-sured.By receiver operating characteristic(ROC)analyses,the area under the curve(AUC),sensitivity,and specificity were obtained to evaluate the diagnostic accuracy of each biomarker and their combinations.Results:This study was conducted on 139 patients with NAFLD-HCC and 345 NAFLD controls.The eleva-tion of these three biomarkers was observed in patients with NAFLD-HCC compared to those in NAFLD controls(all P<0.001).When they were analyzed individually,PIVKA-Ⅱ showed the best performance in diagnosing any-stage HCC with an AUC of 0.869,followed by AFP(0.763;vs.PIVKA-Ⅱ,P<0.001)and AFP-L3(0.689;vs.PIVKA-II,P<0.001).When they were analyzed in combination,AFP+PIVKA-Ⅱ yielded the highest AUC(0.906),followed by AFP+PIVKA-II+AFP-L3(0.904;vs.AFP+PIVKA-Ⅱ,P=0.086),PIVKA-Ⅱ+AFP-L3(0.881;vs.AFP+PIVKA-II,P<0.001),and AFP+AFP-L3(0.759;vs.AFP+PIVKA-II,P<0.001).Similar findings were obtained in the subgroup with early-stage NAFLD-HCC,as well as the non-cirrhotic subgroup.Conclusions:These data validated the better diagnostic ability of PIVKA-II than AFP or AFP-L3 alone for diagnosing any-stage HCC among patients with NAFLD,and the combination of AFP+PIVKA-II signifi-cantly improved the diagnostic accuracy of NAFLD-HCC.