Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies
Background & Aims: We compared the clinical performance of the novel GAAD (gender [biological sex], age, alpha-fetoprotein [AFP], des-gamma carboxyprothrombin [DCP]) and GALAD (gender [biological sex], age, AFP, Lens culinaris agglutinin-reactive AFP [AFP-L3], DCP) algorithms to deduce the c...
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Elsevier
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555924002672 |
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| author | Jinlin Hou Thomas Berg Arndt Vogel Teerha Piratvisuth Jörg Trojan Enrico N. De Toni Masatoshi Kudo Katarina Malinowsky Peter Findeisen Johannes Kolja Hegel Wenzel Schöning Kairat Madin Konstantin Kroeniger Henry Lik-Yuen Chan Ashish Sharma |
| author_facet | Jinlin Hou Thomas Berg Arndt Vogel Teerha Piratvisuth Jörg Trojan Enrico N. De Toni Masatoshi Kudo Katarina Malinowsky Peter Findeisen Johannes Kolja Hegel Wenzel Schöning Kairat Madin Konstantin Kroeniger Henry Lik-Yuen Chan Ashish Sharma |
| author_sort | Jinlin Hou |
| collection | DOAJ |
| description | Background & Aims: We compared the clinical performance of the novel GAAD (gender [biological sex], age, alpha-fetoprotein [AFP], des-gamma carboxyprothrombin [DCP]) and GALAD (gender [biological sex], age, AFP, Lens culinaris agglutinin-reactive AFP [AFP-L3], DCP) algorithms to deduce the clinical utility of AFP-L3 for detecting early-stage hepatocellular carcinoma (HCC) from chronic liver disease (CLD). Methods: An algorithm development study (STOP-HCC-ARP) and clinical validation study (STOP-HCC-MCE) were conducted, recruiting adult participants with HCC (confirmed by radiology or pathology) or CLD in an international, multicenter, case-control design. Serum biomarkers were measured using Elecsys assays (GAAD and GALAD [Cobas]) or μTASWAKO assays (GALAD [μTASWAKO]) while blinded to case/control status. Results: In STOP-HCC-ARP (algorithm development cohort), 1,006 patients {297 HCC (41.4% early-stage [Barcelona Clinic Liver Cancer {BCLC} 0/A) and 709 CLD} were included. Area under the curve (AUCs) for discriminating between early-stage HCC vs. CLD were 91.4%, 91.4%, and 90.8% for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO), respectively. The clinical validation cohort of STOP-HCC-MCE comprised 1,142 patients, (366 HCC cases [48% early-stage], 468 specificity samples and 302 CLD); AUCs for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO) for discriminating between early-stage HCC vs. CLD were 91.4%, 91.5%, and 91.0%, respectively; AUCs were 94.7–95.0% for all-stage HCC. The GAAD and GALAD algorithms demonstrated similar good performance regardless of disease etiology, presence of cirrhosis, geographical region, and within pan-tumor specificity panels (p <0.001). Conclusions: GAAD (Cobas) demonstrated good clinical performance, similar to GALAD (Cobas and μTASWAKO) algorithms, in differentiating HCC and CLD controls, across all disease stages, etiologies, and regions; therefore, AFP-L3 may have a negligible role in GALAD for HCC surveillance. Impact and implications: To improve the detection of early-stage hepatocellular carcinoma (HCC) from benign chronic liver disease (CLD), algorithms combining demographic characteristics and serum biomarkers, such as GAAD and GALAD, have been developed. GAAD combines gender (biological sex), age, alpha-fetoprotein (AFP), des-gamma carboxy-prothrombin (DCP); GALAD combines the same characteristics and biomarkers as GAAD with the addition of Lens culinaris agglutinin-reactive AFP (AFP-L3). Changing disease etiologies and treatment paradigms have raised questions regarding the utility of AFP-L3 in HCC surveillance. Our work demonstrates that the GAAD (Cobas) algorithm demonstrated good clinical performance and was as sensitive and specific as the GALAD (Cobas) and GALAD (μTASWAKO) algorithms in differentiating HCC and CLD controls, across all disease stages, etiologies, and geographical regions; therefore, AFP-L3 may have a negligible role in HCC detection. Our study provides supporting evidence that in participants with CLD undergoing guideline-directed HCC surveillance, the GAAD (Cobas) algorithm may be used as an effective method for the detection of HCC, potentially resulting in improved patient outcomes. |
| format | Article |
| id | doaj-art-129b69402a584b729b47da16510b02b7 |
| institution | Kabale University |
| issn | 2589-5559 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj-art-129b69402a584b729b47da16510b02b72025-02-07T04:48:08ZengElsevierJHEP Reports2589-55592025-02-0172101263Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studiesJinlin Hou0Thomas Berg1Arndt Vogel2Teerha Piratvisuth3Jörg Trojan4Enrico N. De Toni5Masatoshi Kudo6Katarina Malinowsky7Peter Findeisen8Johannes Kolja Hegel9Wenzel Schöning10Kairat Madin11Konstantin Kroeniger12Henry Lik-Yuen Chan13Ashish Sharma14Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou ChinaDivision of Hepatology, Department of Medicine II, University of Leipzig Medical Center, Leipzig, GermanyDepartment of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany (At the time of analysis); Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, Canada; Medical Oncology, Princess Margaret Cancer Centre, Toronto, CanadaDivision of Gastroenterology and Hepatology Department of Medicine, Prince of Songkla University, Hat Yai, ThailandDepartment of Gastroenterology, Goethe Universitaet Frankfurt, Frankfurt, GermanyDepartment of Medicine II, University Hospital, Ludwig Maximilian University of Munich, Munich, GermanyDepartment of Gastroenterology and Hepatology, Kindai University, Osaka, JapanDepartment of Biomarker Services, Microcoat Biotechnologie GmbH, Bernried, GermanyMVZ Labor Dr. Limbach & Kollegen, Heidelberg, GermanyDepartment of Studies, Collaboration and Innovation Management, Labor Berlin Charité Vivantes Services GmbH, Berlin, GermanyDepartment of Surgery, Universitätsmedizin Berlin, Chirurgische Klinik, Campus Charité Mitte and Campus Virchow-Klinikum, Berlin, GermanyGlobal Study Management, Roche Diagnostics GmbH, Penzberg, GermanyClinical Algorithms & Biomarker Statistics, Roche Diagnostics GmbH, Penzberg, GermanyDepartment of Internal Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Corresponding authors. Address: Faculty of Medicine, Choh-Ming Li Basic Medical Sciences Building, The Chinese University of Hong Kong, 32 Tai Po Road, Ma Liu Shui, Hong Kong Special Administrative Region of China, 999077 (H.L.Y. Chan); Clinical Development and Medical Affairs, Roche Diagnostics International AG, Forrenstrasse 2, 6343 Risch-Rotkreuz, Switzerland (A. Sharma).Clinical Development & Medical Affairs, Roche Diagnostics International AG, Rotkreuz, Switzerland; Corresponding authors. Address: Faculty of Medicine, Choh-Ming Li Basic Medical Sciences Building, The Chinese University of Hong Kong, 32 Tai Po Road, Ma Liu Shui, Hong Kong Special Administrative Region of China, 999077 (H.L.Y. Chan); Clinical Development and Medical Affairs, Roche Diagnostics International AG, Forrenstrasse 2, 6343 Risch-Rotkreuz, Switzerland (A. Sharma).Background & Aims: We compared the clinical performance of the novel GAAD (gender [biological sex], age, alpha-fetoprotein [AFP], des-gamma carboxyprothrombin [DCP]) and GALAD (gender [biological sex], age, AFP, Lens culinaris agglutinin-reactive AFP [AFP-L3], DCP) algorithms to deduce the clinical utility of AFP-L3 for detecting early-stage hepatocellular carcinoma (HCC) from chronic liver disease (CLD). Methods: An algorithm development study (STOP-HCC-ARP) and clinical validation study (STOP-HCC-MCE) were conducted, recruiting adult participants with HCC (confirmed by radiology or pathology) or CLD in an international, multicenter, case-control design. Serum biomarkers were measured using Elecsys assays (GAAD and GALAD [Cobas]) or μTASWAKO assays (GALAD [μTASWAKO]) while blinded to case/control status. Results: In STOP-HCC-ARP (algorithm development cohort), 1,006 patients {297 HCC (41.4% early-stage [Barcelona Clinic Liver Cancer {BCLC} 0/A) and 709 CLD} were included. Area under the curve (AUCs) for discriminating between early-stage HCC vs. CLD were 91.4%, 91.4%, and 90.8% for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO), respectively. The clinical validation cohort of STOP-HCC-MCE comprised 1,142 patients, (366 HCC cases [48% early-stage], 468 specificity samples and 302 CLD); AUCs for GAAD (Cobas), GALAD (Cobas), and GALAD (μTASWAKO) for discriminating between early-stage HCC vs. CLD were 91.4%, 91.5%, and 91.0%, respectively; AUCs were 94.7–95.0% for all-stage HCC. The GAAD and GALAD algorithms demonstrated similar good performance regardless of disease etiology, presence of cirrhosis, geographical region, and within pan-tumor specificity panels (p <0.001). Conclusions: GAAD (Cobas) demonstrated good clinical performance, similar to GALAD (Cobas and μTASWAKO) algorithms, in differentiating HCC and CLD controls, across all disease stages, etiologies, and regions; therefore, AFP-L3 may have a negligible role in GALAD for HCC surveillance. Impact and implications: To improve the detection of early-stage hepatocellular carcinoma (HCC) from benign chronic liver disease (CLD), algorithms combining demographic characteristics and serum biomarkers, such as GAAD and GALAD, have been developed. GAAD combines gender (biological sex), age, alpha-fetoprotein (AFP), des-gamma carboxy-prothrombin (DCP); GALAD combines the same characteristics and biomarkers as GAAD with the addition of Lens culinaris agglutinin-reactive AFP (AFP-L3). Changing disease etiologies and treatment paradigms have raised questions regarding the utility of AFP-L3 in HCC surveillance. Our work demonstrates that the GAAD (Cobas) algorithm demonstrated good clinical performance and was as sensitive and specific as the GALAD (Cobas) and GALAD (μTASWAKO) algorithms in differentiating HCC and CLD controls, across all disease stages, etiologies, and geographical regions; therefore, AFP-L3 may have a negligible role in HCC detection. Our study provides supporting evidence that in participants with CLD undergoing guideline-directed HCC surveillance, the GAAD (Cobas) algorithm may be used as an effective method for the detection of HCC, potentially resulting in improved patient outcomes.http://www.sciencedirect.com/science/article/pii/S2589555924002672Hepatocellular carcinomaSurveillanceAlgorithmGAADGALAD |
| spellingShingle | Jinlin Hou Thomas Berg Arndt Vogel Teerha Piratvisuth Jörg Trojan Enrico N. De Toni Masatoshi Kudo Katarina Malinowsky Peter Findeisen Johannes Kolja Hegel Wenzel Schöning Kairat Madin Konstantin Kroeniger Henry Lik-Yuen Chan Ashish Sharma Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies JHEP Reports Hepatocellular carcinoma Surveillance Algorithm GAAD GALAD |
| title | Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies |
| title_full | Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies |
| title_fullStr | Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies |
| title_full_unstemmed | Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies |
| title_short | Comparative evaluation of multimarker algorithms for early-stage HCC detection in multicenter prospective studies |
| title_sort | comparative evaluation of multimarker algorithms for early stage hcc detection in multicenter prospective studies |
| topic | Hepatocellular carcinoma Surveillance Algorithm GAAD GALAD |
| url | http://www.sciencedirect.com/science/article/pii/S2589555924002672 |
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