BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening program...BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.展开更多
基金Supported by Sara Borrell postdoctoral fellowships from Instituto de Salud Carlos Ⅲ to support ángela Rojas postdoctoral contract,Consejería de Salud y Familias,Junta de Andalucía supporting Antonio Gil-Gómez contract,PI19/01404 Grant from Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,PI19/00589/Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,and the Xeptagen,Italy,provided the ELISA kits for the measurements of SCCA-IgM.
文摘BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.
