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World J Gastroenterol. Jan 14, 2022; 28(2): 216-229
Published online Jan 14, 2022. doi: 10.3748/wjg.v28.i2.216
Update on the applications and limitations of alpha-fetoprotein for hepatocellular carcinoma
Hira Hanif, Mukarram Jamat Ali, Ammu T Susheela, Iman Waheed Khan, Maria Alejandra Luna-Cuadros, Muzammil Muhammad Khan, Daryl Tan-Yeung Lau
Hira Hanif, Mukarram Jamat Ali, Iman Waheed Khan, Maria Alejandra Luna-Cuadros, Muzammil Muhammad Khan, Daryl Tan-Yeung Lau, Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
Ammu T Susheela, Internal Medicine, Loyola MacNeal Hospital, Berwyn, PA 60402, United States
Author contributions: Hanif H and Ali MJ contributed equally; Lau DTY provided the concept and direction of the review, the learning points and the editing of the manuscript; Khan MM, Hanif H, Ali MJ, Susheela AT, and Luna-Cuadros MA reviewed the literature and wrote the first manuscript draft; Khan IW and Ali MJ contributed to the addition of literature, revision and edition of the final manuscript; Khan MM and Lau DTY are joint senior authors.
Conflict-of-interest statement: There is no conflict of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Daryl Tan-Yeung Lau, MD, MSc, Associate Professor, Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St. Liver Research Center, Suite 4A, Boston, MA 02215, United States. dlau@bidmc.harvard.edu
Received: October 4, 2021
Peer-review started: October 4, 2021
First decision: October 20, 2021
Revised: November 26, 2021
Accepted: December 31, 2021
Article in press: December 31, 2021
Published online: January 14, 2022
Processing time: 98 Days and 11.2 Hours
Abstract

Alpha-fetoprotein (AFP) is an oncofetal glycoprotein that has been used as a tumor marker for hepatocellular carcinoma (HCC) in combination with ultrasound and other imaging modalities. Its utility is limited because of both low sensitivity and specificity, and discrepancies among the different methods of measurements. Moreover, its accuracy varies according to patient characteristics and the AFP cut-off values used. Combination of AFP with novel biomarkers such as AFP-L3, Golgi specific membrane protein (GP73) and des-gamma-carboxyprothrombin significantly improved its accuracy in detecting HCC. Increased AFP level could also signify severity of hepatic destruction and subsequent regeneration and is commonly observed in patients with acute and chronic liver conditions and cirrhosis. Hereditary and other non-hepatic disorders can also cause AFP elevation.

Keywords: Alpha-fetoprotein; Hepatocellular carcinoma; Alpha-fetoprotein-L3; Cirrhosis; Tumor markers; Hereditary persistence of alpha-fetoprotein

Core Tip: Alpha-fetoprotein has been used commonly as a biomarker for hepatocellular carcinoma (HCC) surveillance. Its sensitivity and specificity can be affected by the assay methods, patient characteristics and severity of the underlying liver conditions. Combination with other novel markers has shown promising results. Algorithms integrating these serum markers with noninvasive diagnostic imaging modalities are essential for the accurate and timely diagnosis of HCC.