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
Ming-Cheng Guan a ,# , Wei Ouyang a ,# , Si-Yu Liu b ,# , Li-Yang Sun c ,# , Wei-Yue Chen b ,d , Xiang-Min Tong b ,c ,e , Hong Zhu a ,∗, Tian Yang c ,e ,f ,∗
a Department of Medical Oncology, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
b Department of Laboratory, Zhejiang University Lishui Hospital, Lishui 323000, China
c Department of Hepatobiliary, Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
d 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
e School of Clinical Medicine, Hangzhou Medical College, Hangzhou 310059, China
f Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai 200438, China
∗Corresponding authors at: Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai 200438, China.
E-mail addresses: zhuhong_jasmine@suda.edu.cn (H. Zhu), yangtiandfgd@hotmail.com (T. Yang).
# Contributed equally.
Abstract：Background: 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.
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 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.
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.
. [J]. Hepatobiliary Pancreat Dis Int, 2022, 21(6): 559-568.
Guan MC, Ouyang W, Liu SY, Sun LY, Chen WY, Tong XM, Zhu H, Yang T. 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. Hepatobiliary Pancreat Dis Int, 2022, 21(6): 559-568.
2022, Vol. 21 
