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. 2023 Dec;79(6):1469-1477.
doi: 10.1016/j.jhep.2023.08.020. Epub 2023 Sep 7.

AFP-L3 and DCP strongly predict early hepatocellular carcinoma recurrence after liver transplantation

Joshua S Norman  1 , P Jonathan Li  2 , Prashant Kotwani  3 , Amy M Shui  4 , Francis Yao  3 , Neil Mehta  5
Affiliations

AFP-L3 and DCP strongly predict early hepatocellular carcinoma recurrence after liver transplantation

Joshua S Norman et al. J Hepatol. 2023 Dec.

Abstract

Background & aims: Alpha-fetoprotein (AFP) predicts hepatocellular carcinoma (HCC) recurrence after liver transplant (LT) but remains an imperfect biomarker. The role of DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) in predicting HCC recurrence remains incompletely characterized. AFP-L3 and DCP could identify patients at high risk of post-transplant HCC recurrence and serve as liver transplant exclusion criteria to defer transplant until patients receive additional risk-reducing pre-transplant locoregional therapy.

Methods: This prospective cohort study included consecutive patients with HCC who underwent LT (within or down-staged to Milan criteria) between 2017 and 2022. Pre-transplant AFP, AFP-L3, and DCP measurements were obtained. The primary endpoint was the ability of biomarkers to predict HCC recurrence-free survival.

Results: This cohort included 285 patients with a median age of 67 (IQR 63-71). At LT, median biomarker values were AFP 5.0 ng/ml (IQR 3.0-12.1), AFP-L3 6.7% (0.5-13.2), and DCP 1.0 ng/ml (0.3-2.8). Most (94.7%) patients received pre-LT locoregional therapy. After a median post-LT follow-up of 3.1 years, HCC recurrence was observed in 18 (6.3%) patients. AFP-L3 and DCP outperformed AFP with C-statistics of 0.81 and 0.86 respectively, compared with 0.74 for AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted 61.1% of HCC recurrences, whereas HCC only recurred in 7 of 265 (2.6%) patients not meeting this threshold. The Kaplan-Meier recurrence-free survival rate at 3 years post-LT was 43.7% for patients with dual-positive biomarkers compared to 97.0% for all others (p <0.001).

Conclusions: Dual-positivity for AFP-L3 ≥15% and DCP ≥7.5 strongly predicted post-LT HCC recurrence. This model could refine LT selection criteria and identify high-risk patients who require additional locoregional therapy prior to LT.

Impact and implications: Alpha-fetoprotein (AFP) is used to predict hepatocellular carcinoma (HCC) recurrence after liver transplant, but it remains an imperfect biomarker. In this prospective study, the biomarkers DCP (des-gamma-carboxyprothrombin) and AFP-L3 (AFP bound to Lens culinaris agglutinin) strongly predicted early HCC recurrence and outperformed AFP. A dual-biomarker combination of AFP-L3 ≥15% and DCP ≥7.5 predicted the majority of recurrences and could be used to further refine liver transplant eligibility criteria.

Keywords: AFP-L3; alpha fetoprotein (AFP); des-gamma-carboxyprothrombin (DCP); hepatocellular carcinoma (HCC); liver transplant (LT).

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Conflict of interest statement

Neil Mehta has served on advisory boards for WAKO Diagnostics and has received institutional research funding from WAKO Diagnostics, Glycotest, and Target Pharmasolutions. Francis Yao has received institutional research funding from WAKO Diagnostics. None of the other authors have any relevant potential conflicts of interest to disclose.

Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

Fig. 1.
Fig. 1.. Relationships of AFP-L3 and DCP with HCC recurrence.
(A) Area under the receiver-operating characteristics curves for continuous AFP, AFP-L3, and DCP relationship with recurrence (n = 285). (B) Relationship between AFP-L3 and DCP values stratified by HCC recurrence. Low (AFP-L3 ≥15% and DCP ≥7.5 ng/ml) cut-off represented by short-dashed line. High (AFP-L3 ≥25% and DCP ≥15 ng/ml) dual biomarker positive model represented by the dash-dot line. AFP, alpha-fetoprotein; AFP-L3, AFP bound to Lens culinaris agglutinin; DCP, des-gamma-carboxyprothrombin.
Fig. 2.
Fig. 2.. Kaplan-Meier survival estimates of single biomarker thresholds.
(A) AFP ≥100 ng/ml (B) AFP-L3 ≥15% (C) DCP ≥7.5 ng/ml. AFP, alpha-fetoprotein; AFP-L3, AFP bound to Lens culinaris agglutinin; DCP, des-gamma-carboxyprothrombin.
Fig. 3.
Fig. 3.. Kaplan-Meier survival estimates of dual-positive biomarker thresholds.
(A) AFP-L3 ≥15% and DCP ≥7.5 ng/ml (B) AFP-L3 ≥25% and DCP ≥15 ng/ml. AFP, alpha-fetoprotein; AFP-L3, AFP bound to Lens culinaris agglutinin; DCP, des-gamma-carboxyprothrombin.
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