Abstract
Purpose
Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma during antiviral therapy. We aimed to clarify the values of alpha-fetoprotein (AFP), lectin-reactive fraction of AFP (AFP-L3), and des-γ-carboxyprothrombin (DCP) for early warning of HCC.
Methods
A total of 1348 CHB patients received antiviral therapy and follow-up every 26 weeks. Eighty-four patients with HCC were age-, sex-, and cirrhosis-matched with 168 controls. AFP, AFP-L3, and DCP were compared between the groups from 104 weeks before HCC diagnosis (− 104 w) to the time of diagnosis (0 w).
Results
Of the 84 HCC patients, 60 (71.4%) had early-stage HCC, AFP increased from − 26 w, and AFP-L3 and DCP increased from − 78 w. However, levels were unchanged in controls. ΔAFP, ΔAFP-L3, and ΔDCP showed similar abilities for predicting HCC (P > 0.05). Receiver operating characteristic curve analysis showed that AFP had better diagnostic performance for HCC than AFP-L3, DCP, or their combination. The cut-off values of AFP, AFP-L3, and DCP were 5.3 ng/mL, 1.05%, and 31.5 mAU/mL, respectively. Notably, lower AFP values were required to diagnose HCC in patients with detectable HBV DNA (4.1 ng/mL) or elevated alanine aminotransferase (5.2 ng/mL).
Conclusions
Changes in AFP, AFP-L3, and DCP can help to predict HCC in CHB patients receiving antiviral therapy. A lower AFP value is needed to diagnose HCC, especially in patients with detectable HBV DNA or elevated alanine aminotransferase.
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Acknowledgements
We thank Susan Furness, Ph.D., from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the English text of a draft of this manuscript.
Funding
National Science and Technology Major Project (2017ZX10202202, 2013ZX10002004).
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Study design (HM, HY), data collection (QZ, JZ, HL, HW, JR, SS, MY, HY, HM), statistical analysis of data (QZ, SW), manuscript writing (QZ, JZ), serum measurement (MC, KW), critical revision of the manuscript (HM, HY). All authors have made a significant contribution to this study and have approved the final manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Medical Ethics Committee of Beijing Friendship Hospital, Capital Medical University (Beijing, China, 2020-P2-194-01) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The requirement for informed consent was waived due to the retrospective nature of the study. Our study was purely observational and not required for clinical trial registration.
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Zhu, Q., Zhou, J., Li, H. et al. Dynamic changes in three biomarkers predict early-stage hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy. J Cancer Res Clin Oncol 149, 12691–12701 (2023). https://doi.org/10.1007/s00432-023-05024-2
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DOI: https://doi.org/10.1007/s00432-023-05024-2