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Peer-reviewedCC BY-NCMedicine

Association between alpha-fetoprotein elevation and recurrence in patients who achieved normalized alpha-fetoprotein after curative resection for hepatocellular carcinoma : A retrospective cohort study

  • Jeong Ah Hwang1
  • Jisun Lee2
  • Kyung Sik Yi2
  • Chi-Hoon Choi2
  • Kil Sun Park3
  • Ji Hye Min1
  1. 1Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  2. 2Department of Radiology, College of Medicine, Chungbuk National University, Chungbuk National University Hospital, Cheongju, Republic of Korea
  3. 3Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea.
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Abstract

Alpha-fetoprotein (AFP) is a cornerstone biomarker for hepatocellular carcinoma (HCC) surveillance following curative resection. Although AFP normalization generally indicates effective tumor control, subsequent AFP elevation poses a diagnostic dilemma due to its potential association with both tumor recurrence and nonneoplastic liver conditions. This study aimed to determine the factors influencing AFP elevation and to assess the role of serial AFP testing for the early detection of recurrent HCC, thereby addressing an unmet need in refining postoperative surveillance strategies. In this retrospective cohort study, 705 patients who underwent curative resection for HCC between January 2018 and March 2020 and achieved AFP normalization were analyzed. Postoperative surveillance included AFP and imaging exams, with AFP elevation defined as ≥ 20 ng/mL and normalization as AFP < 20 ng/mL post-surgery. Multivariable analysis identified factors associated with AFP elevation. Recurrence occurred in 34.6%. Independent factors associated with AFP elevation included recurrence (odds ratio [OR] = 21.9; 95% confidence interval [CI] = 7.5–64.2), preoperative AFP elevation (OR = 3.6; 95% CI = 1.7–7.6), logAFP at normalization (OR = 12.7; 95% CI = 3.5–45.7), and cirrhosis (OR = 2.2; 95% CI = 1.0–4.5). In patients without recurrence, logAFP at normalization (OR = 12.6; 95% CI = 3.7–43.4) and cirrhosis (OR = 2.2; 95% CI = 1.1–4.5) were independently associated with false positive elevation. Intrahepatic recurrence accounted for 69.2%, with lesions of ≤ 1 cm composing 88.9%. Following a preceding AFP elevation, recurrence was detected after a median of 4.8 months and within 12 months in all cases. AFP elevation during postoperative surveillance is a strong indicator of HCC recurrence. In cases where AFP elevation occurs without clear radiologic evidence of recurrence, early and frequent liver MRI (at intervals of ≤ 3 months for at least 12 months) is recommended to facilitate prompt detection of intrahepatic lesions. Moreover, clinicians should be mindful that elevated normalized AFP levels and underlying cirrhosis increase the risk of false positive elevations. These findings underscore the need for a tailored surveillance strategy to optimize the early diagnosis and management of recurrent HCC.

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Cite

BibTeXRIS
BibTeX
@article{hwang2026association,
  title = {{Association between alpha-fetoprotein elevation and recurrence in patients who achieved normalized alpha-fetoprotein after curative resection for hepatocellular carcinoma : A retrospective cohort study}},
  author = {Jeong Ah Hwang and Jisun Lee and Kyung Sik Yi and Chi-Hoon Choi and Kil Sun Park and Ji Hye Min},
  journal = {Medicine},
  year = {2026},
  month = oct,
  doi = {10.1097/md.0000000000051346},
  url = {https://europepmc.org/article/PMC/PMC13727215},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Association between alpha-fetoprotein elevation and recurrence in patients who achieved normalized alpha-fetoprotein after curative resection for hepatocellular carcinoma : A retrospective cohort study
AU  - Jeong Ah Hwang
AU  - Jisun Lee
AU  - Kyung Sik Yi
AU  - Chi-Hoon Choi
AU  - Kil Sun Park
AU  - Ji Hye Min
PY  - 2026
DA  - 2026/10/30
JO  - Medicine
DO  - 10.1097/md.0000000000051346
UR  - https://europepmc.org/article/PMC/PMC13727215
AB  - Alpha-fetoprotein (AFP) is a cornerstone biomarker for hepatocellular carcinoma (HCC) surveillance following curative resection. Although AFP normalization generally indicates effective tumor control, subsequent AFP elevation poses a diagnostic dilemma due to its potential association with both tumor recurrence and nonneoplastic liver conditions. This study aimed to determine the factors influencing AFP elevation and to assess the role of serial AFP testing for the early detection of recurrent HCC, thereby addressing an unmet need in refining postoperative surveillance strategies. In this retrospective cohort study, 705 patients who underwent curative resection for HCC between January 2018 and March 2020 and achieved AFP normalization were analyzed. Postoperative surveillance included AFP and imaging exams, with AFP elevation defined as ≥ 20 ng/mL and normalization as AFP < 20 ng/mL post-surgery. Multivariable analysis identified factors associated with AFP elevation. Recurrence occurred in 34.6%. Independent factors associated with AFP elevation included recurrence (odds ratio [OR] = 21.9; 95% confidence interval [CI] = 7.5–64.2), preoperative AFP elevation (OR = 3.6; 95% CI = 1.7–7.6), logAFP at normalization (OR = 12.7; 95% CI = 3.5–45.7), and cirrhosis (OR = 2.2; 95% CI = 1.0–4.5). In patients without recurrence, logAFP at normalization (OR = 12.6; 95% CI = 3.7–43.4) and cirrhosis (OR = 2.2; 95% CI = 1.1–4.5) were independently associated with false positive elevation. Intrahepatic recurrence accounted for 69.2%, with lesions of ≤ 1 cm composing 88.9%. Following a preceding AFP elevation, recurrence was detected after a median of 4.8 months and within 12 months in all cases. AFP elevation during postoperative surveillance is a strong indicator of HCC recurrence. In cases where AFP elevation occurs without clear radiologic evidence of recurrence, early and frequent liver MRI (at intervals of ≤ 3 months for at least 12 months) is recommended to facilitate prompt detection of intrahepatic lesions. Moreover, clinicians should be mindful that elevated normalized AFP levels and underlying cirrhosis increase the risk of false positive elevations. These findings underscore the need for a tailored surveillance strategy to optimize the early diagnosis and management of recurrent HCC.
SN  - 0304-5412
SN  - 1536-5964
SN  - 0025-7974
ER  -