Abstract

Background: There is limited data on the utility of the percentage of lens culinaris agglutininreactive α-fetoprotein (AFP-L3%) measured on the new μTASWako i30 Immunoanalyzer for the diagnosis of early stage HCC in the U.S. population. The utility of AFP, AFP-L3% or des-γ-carboxy prothrombin (DCP) for predictingHCC recurrence after liver transplantation is also unknown. Aims: To 1) determine the sensitivity and specificity of AFP, AFP-L3%, and DCP for the diagnosis of early stage HCC; and 2) evaluate the utility of AFP, AFP-L3% and DCP in predicting HCC recurrence after orthotopic liver transplantation (OLT). Methods: Three hundred and thirteen HCC patients and 307 non-HCC controls with end-stage liver disease who were transplanted at Mayo Clinic, Rochester, MN and Jacksonville, FL between 2000 2008 and had serum samples available for biomarker testing were included in the study. Demographic and clinical information were abstracted from the medical record. AFP, AFP-L3% and des-γ-carboxy prothrombin (DCP) assays were performed on the μTASWako i30 Immunoanalyzer. Receiver operating characteristic (ROC) curves were generated to determine the sensitivity and specificity of the biomarkers for diagnosis of HCC. Predictors of HCC development and HCC recurrence were analyzed using the Logistic regression model. Results: AFP had the best area under the ROC curve (0.75, 95%CI 0.72-0.78) for diagnosis of early stage HCC, followed by AFP-L3% (0.63, 95% CI 0.60-0.66) and DCP (0.46, 95%CI 0.43-0.49). The optimum cut-off value of AFP was 9.4 ng/ml with the sensitivity of 62.6% and specificity of 80% and of AFP-L3% was 15.8% with a sensitivity of 30.1% and specificity of 85.1%. AFP and AFP-L3% were independently associated with early stage HCC. Every 10 ng/mL increase in AFP value and every 10% increase in AFP-L3% value were associated with a 36.6% and 43.0% increased risk for HCC diagnosis (OR=1.37, 95%CI 1.20-1.56 for AFP, p,0.0001,and OR 1.43, 95% CI 1.18-1.58 for AFP-L3%, p,0.0001). Of the 313 HCC patients, 301 (96.2%) patients were treated with transarterial chemoembolization (TACE) prior to transplantation. Forty-seven (15%) patients had HCC recurrence after transplant (median time for recurrence was 18.4 months). The post-TACE pre-OLT AFP-L3% was significantly associated with HCC recurrence after OLT. Every 10% increase in post-TACE AFP-L3 was associated with a 48.2% increased risk of HCC recurrence after OLT (OR=1.48, 95% CI 1.11 to 1.97, p=0.007). AFP, AFP-L3% and DCP at the time of HCC diagnosis were not associated with HCC recurrence after OLT. Conclusions: AFP-L3% is potentially useful in predicting HCC recurrence after liver transplantation in US patients. Validation of these results in additional cohorts is needed.

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