Gastroenterology

Gastroenterology

Volume 137, Issue 1, July 2009, Pages 110-118
Gastroenterology

Clinical Advances in Liver, Pancreas, and Biliary Tract
α-Fetoprotein, Des-γ Carboxyprothrombin, and Lectin-Bound α-Fetoprotein in Early Hepatocellular Carcinoma

https://doi.org/10.1053/j.gastro.2009.04.005Get rights and content

Background & Aims

α-Fetoprotein (AFP) is widely used as a surveillance test for hepatocellular carcinoma (HCC) among patients with cirrhosis. Des-γ carboxy-prothrombin (DCP) and lectin-bound AFP (AFP-L3%) are potential surveillance tests for HCC. The aims of this study were to determine performance of DCP and AFP-L3% for the diagnosis of early HCC; whether they complement AFP; and what factors affect DCP, AFP-L3%, or AFP levels.

Methods

We conducted a large phase 2 biomarker case-control study in 7 academic medical centers in the United States. Controls were patients with compensated cirrhosis and cases were patients with HCC. AFP, DCP, and AFP-L3% levels were measured blinded to clinical data in a central reference laboratory.

Results

A total of 836 patients were enrolled: 417 (50%) were cirrhosis controls and 419 (50%) were HCC cases, of which 208 (49.6%) had early stage HCC (n = 77 very early, n = 131 early). AFP had the best area under the receiver operating characteristic curve (0.80, 95% confidence interval [CI]: 0.77–0.84), followed by DCP (0.72, 95% CI: 0.68–0.77) and AFP-L3% (0.66, 95% CI: 0.62–0.70) for early stage HCC. The optimal AFP cutoff value was 10.9 ng/mL leading to a sensitivity of 66%. When only those with very early HCC were evaluated, the area under the receiver operating characteristic curve for AFP was 0.78 (95% CI: 0.72–0.85) leading to a sensitivity of 65% at the same cutoff.

Conclusions

AFP was more sensitive than DCP and AFP-L3% for the diagnosis of early and very early stage HCC at a new cutoff of 10.9 ng/mL.

Section snippets

Study Design

We performed a large, EDRN-defined, phase 2 biomarker case-control study. Cases included consecutive adult patients with HCC seen between February 2005 and August 2007 at 7 medical centers in the United States (University of Michigan, Mayo Clinic-Minnesota, Mayo Clinic-Florida, Mt. Sinai Medical Center-New York, University of Pennsylvania, Saint Louis University, and Stanford University). Assays were performed at the University of California at Los Angeles in a blinded fashion to clinical data,

Patient Characteristics

A total of 859 patients were approached. Five cases and 18 controls were excluded because of the sample not being collected according to protocol or because they did not meet eligibility criteria. A total of 836 patients were included in this study, of which 417 (50%) were cirrhosis controls without HCC and 419 (50%) were HCC cases. Of the cases, 208 (49.6%) were considered early stage HCC: BCLC stage A (n = 131, 63%) and BCLC stage 0 (n = 77, 37%). The characteristics of these patients are

Discussion

In the largest study of biomarkers for the diagnosis of early stage HCC, we showed that AFP had a sensitivity of 66% and specificity of 81%, at a new cutoff of 10.9 ng/mL. AFP had the best AUC in tumors at the BCLC stage 0 and BCLC states A when compared with other markers. Importantly, AFP had the best performance of all the markers for BCLC stage 0 HCC, the detection of which is the main goal of a surveillance program.

AFP has been the most widely utilized serologic test for HCC. In a previous

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by Early Detection Research Network of the National Cancer Institute (CA-084986), by grant DK064909 (to J.A.M), and by test kits provided by Wako Diagnostics and Eisai.

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