Validation and optimization of AFP-based biomarker panels for early HCC detection in Latin America and Europe

被引:11
作者
Beudeker, Boris J. B. [1 ]
Fu, Siyu [1 ]
Balderramo, Domingo [2 ]
Mattos, Angelo Z. [3 ]
Carrera, Enrique [4 ]
Diaz, Javier [5 ]
Prieto, Jhon [6 ]
Banales, Jesus [7 ,8 ]
Vogel, Arndt [9 ]
Arrese, Marco [10 ]
Oliveira, Jeffrey [1 ]
Groothuismink, Zwier M. A. [1 ]
van Oord, Gertine [1 ]
Hansen, Bettina E. [1 ,11 ,12 ,13 ]
de Man, Robert A. [1 ]
Debes, Jose D. [1 ,14 ]
Boonstra, Andre [1 ,15 ,16 ]
机构
[1] Erasmus MC Univ Med Ctr, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands
[2] Hosp Privado Univ Cordoba, Inst Univ Ciencias Biomed Cordoba, Dept Gastroenterol, Cordoba, Argentina
[3] Fed Univ Hlth Sci Porto Alegre, Grad Program Med Hepatol, Porto Alegre, Brazil
[4] Hosp Eugenio Espejo, Dept Gastroenterol & Hepatol, Quito, Ecuador
[5] Hosp Nacl Edgardo Rebagliati Martins, Dept Gastroenterol, HNERM, Lima, Peru
[6] Ctr Enfermedades Hepat & Digest CEHYD, Bogota, Colombia
[7] Univ Basque Country UPV EHU, Donostia Univ Hosp, Biodonostia Hlth Res Inst, Dept Liver & Gastrointestinal Dis, San Sebastian, Spain
[8] Univ Navarra, Sch Sci, Dept Biochem & Genet, Pamplona, Spain
[9] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany
[10] Pontificia Univ Catolica Chile, Dept Gastroenterol, Santiago, Chile
[11] Erasmus MC Univ Med Ctr, Dept Epidemiol, Biostat, Rotterdam, Netherlands
[12] Univ Toronto, IHPME, Toronto, ON, Canada
[13] Univ Hlth Network, Toronto Ctr Liver Dis, Toronto, ON, Canada
[14] Univ Minnesota, Dept Med, Minneapolis, MN USA
[15] Wytemaweg 80, NL-3015 CN Rotterdam, Netherlands
[16] Postbus 2040, NL-3000 CA Rotterdam, Netherlands
基金
欧盟地平线“2020”;
关键词
HEPATOCELLULAR-CARCINOMA; HIGH-SENSITIVITY; GALAD;
D O I
10.1097/HC9.0000000000000264
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: HCC is a major cause of cancer death worldwide. Serum biomarkers such as alpha-fetoprotein (AFP), protein induced by vitamin K absence-II, and the Gender, Age, AFP-L3, AFP, Des-gamma-carboxy prothrombin (GALAD) score have been recommended for HCC surveillance. However, inconsistent recommendations in international guidelines limit their clinical utility.Methods: In this multicenter study, over 2000 patient samples were collected in 6 Latin American and 2 European countries. The performance of the GALAD score was validated in cirrhotic cases, and optimized versions were tested for early-stage HCC and prediagnostic HCC detection.Results: The GALAD score could distinguish between HCC and cirrhosis in Latin American patients with an AUC of 0.76, sensitivity of 70%, and specificity of 83% at the conventional cutoff value of -0.63. In a European cohort, GALAD had an AUC of 0.69, sensitivity of 66%, and specificity of 72%. Optimizing the score in the 2 large multicenter cohorts revealed that AFP-L3 contributed minimally to early-stage HCC detection. Thus, we developed a modified GALAD score without AFP-L3, the ASAP (age, sex, AFP, and protein induced by vitamin K absence-II), which showed promise for early-stage HCC detection upon validation. The ASAP score also identified patients with cirrhosis at high risk for advanced-stage HCC up to 15 months before diagnosis (p < 0.0001) and differentiated HCC from hemangiomas, with a specificity of 100% at 71% sensitivity.Conclusion: Our comprehensive analysis of large sample cohorts validates the GALAD score's utility in Latin American, Spanish, and Dutch patients for early-stage HCC detection. The optimized GALAD without AFP-L3, the ASAP score, is a good alternative and shows greater promise for HCC prediction.
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页数:11
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