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AFP-L3 and DCP are superior to AFP in predicting waitlist dropout in HCC patients: Results of a prospective study
Neil Mehta1, Prashant Kotwani1, Joshua Norman1
1Division of Gastroenterology, Department of Medicine, University of California, San Francisco, California, USA.
Insights
Alpha-fetoprotein lectin-3 (AFP-L3) and des-gamma-carboxyprothrombin (DCP) predict liver cancer transplant waitlist dropout better than AFP. High levels of both AFP-L3 and DCP indicate a 100% risk of dropout.
Area of Science:
- Hepatology
- Oncology
- Transplantation Medicine
Background:
- Alpha-fetoprotein (AFP) is a standard biomarker for hepatocellular carcinoma (HCC) prognosis.
- Novel biomarkers are needed to predict liver transplantation (LT) waitlist dropout in HCC patients.
- The predictive value of AFP lectin-3 (AFP-L3) and des-gamma-carboxyprothrombin (DCP) for waitlist dropout is currently unknown.
Purpose of the Study:
- To evaluate the efficacy of AFP, AFP-L3, and DCP as biomarkers for predicting waitlist dropout in HCC patients awaiting LT.
- To compare the prognostic value of these biomarkers against AFP alone.
Main Methods:
- Prospective single-center study of 267 HCC patients listed for LT.
- Measurement of AFP, AFP-L3, and DCP at the time of LT listing.
- Follow-up for waitlist dropout, LT, or ongoing waitlist status.
- Cox proportional hazards analysis and Kaplan-Meier survival analysis.
Main Results:
- AFP-L3 (≥35%) and DCP (≥7.5 ng/mL) were significantly associated with increased waitlist dropout.
- AFP levels, across tested cutoffs, did not predict waitlist dropout.
- Multivariable analysis confirmed AFP-L3 and DCP as independent predictors of dropout, alongside time to listing and MELD-Na score.
- Patients with both AFP-L3 ≥35% and DCP ≥7.5 ng/mL had a 100% probability of waitlist dropout within 2 years.
Conclusions:
- AFP-L3 and DCP are superior to AFP in predicting waitlist dropout for HCC patients awaiting LT.
- The combination of elevated AFP-L3 and DCP levels provides significant prognostic value, identifying patients at highest risk of waitlist dropout.
Abstract:
In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0 ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5 ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.
