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

• Published in: Hepatobiliary & pancreatic diseases international Vol. 21; no. 6; pp. 559 - 568
• Main Authors: Guan, Ming-Cheng, Ouyang, Wei, Liu, Si-Yu, Sun, Li-Yang, Chen, Wei-Yue, Tong, Xiang-Min, Zhu, Hong, Yang, Tian
• Format: Journal Article
• Language: English
• Published: Singapore Elsevier B.V 01.12.2022; Department of Hepatobiliary,Pancreatic and Minimal Invasive Surgery,Zhejiang Provincial People's Hospital,People's Hospital of Hangzhou Medical College,Hangzhou 310014,China; School of Clinical Medicine,Hangzhou Medical College,Hangzhou 310059,China; The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province,Department of Interventional Radiology,Zhejiang University Lishui Hospital,Lishui 323000,China%Department of Laboratory,Zhejiang University Lishui Hospital,Lishui 323000,China; Department of Hepatobiliary Surgery,Eastern Hepatobiliary Surgery Hospital,Second Military Medical University(Navy Medical University),Shanghai 200438,China; School of Clinical Medicine,Hangzhou Medical College,Hangzhou 310059,China%Department of Hepatobiliary,Pancreatic and Minimal Invasive Surgery,Zhejiang Provincial People's Hospital,People's Hospital of Hangzhou Medical College,Hangzhou 310014,China; Department of Medical Oncology,the First Affiliated Hospital of Soochow University,Suzhou 215006,China%Department of Laboratory,Zhejiang University Lishui Hospital,Lishui 323000,China%Department of Hepatobiliary,Pancreatic and Minimal Invasive Surgery,Zhejiang Provincial People's Hospital,People's Hospital of Hangzhou Medical College,Hangzhou 310014,China%Department of Laboratory,Zhejiang University Lishui Hospital,Lishui 323000,China
• Subjects: Alpha-fetoprotein; Hepatocellular carcinoma; Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein; Nonalcoholic fatty liver disease; Protein induced by vitamin K absence or antagonist-II; Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein; Hepatocellular carcinoma; Nonalcoholic fatty liver disease; Protein induced by vitamin K absence or antagonist-II; Alpha-fetoprotein; Protein induced by vitamin K absence or antagonist-
• ISSN: 1499-3872
• DOI: 10.1016/j.hbpd.2022.05.003

Current surveillance strategies for hepatocellular carcinoma (HCC) among patients with nonalcoholic fatty liver disease (NAFLD) are insufficient. This study aimed to investigate the diagnostic performance 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. Serologic AFP, AFP-L3, and PIVKA-II levels in NAFLD patients with and without HCC were measured. 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. This study was conducted on 139 patients with NAFLD-HCC and 345 NAFLD controls. The elevation 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. 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 significantly improved the diagnostic accuracy of NAFLD-HCC.